# Highly Robust and Efficient Blechert-Type Cyclic(alkyl)(amino)carbene Ruthenium Complexes for Olefin Metathesis

Antonio del Vecchio, Jakub Talcik, Sophie Colombel-Rouen, Jan Lorkowski, Melinda R Serrato, Thierry Roisnel, Nicolas Vanthuyne, Guy Bertrand, Rodolphe Jazzar, Marc Mauduit

► To cite this version:

Antonio del Vecchio, Jakub Talcik, Sophie Colombel-Rouen, Jan Lorkowski, Melinda R Serrato, et al. Highly Robust and Efficient Blechert-Type Cyclic(alkyl)(amino)carbene Ruthenium Complexes for Olefin Metathesis. ACS Catalysis, 2023, 13 (9), pp.6195-6202. 10.1021/acscatal.3c01208. hal-04115781

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# Highly Robust and Efficient Blechert-Type Cyclic(alkyl)(amino)carbene Ruthenium Complexes for Olefin Metathesis

Antonio del Vecchio, Jakub Talcik, Sophie Colombel-Rouen, Jan Lorkowski, Melinda R Serrato, Thierry Roisnel, Nicolas Vanthuyne, Guy Bertrand, Rodolphe Jazzar, Marc Mauduit

<figure><img src="image_1.png" /></figure>

To cite this version:

Antonio del Vecchio, Jakub Talcik, Sophie Colombel-Rouen, Jan Lorkowski, Melinda R Serrato, et al. Highly Robust and Efficient Blechert-Type Cyclic(alkyl)(amino)carbene Ruthenium Complexes for Olefin Metathesis. ACS Catalysis, 2023, 13 (9), pp.6195-6202. 10.1021/acscatal.3c01208. hal-04115781

HAL Id: hal-04115781

https://hal.science/hal-04115781v1

Submitted on 30 Jan 2024

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_2.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
**Title**

Highly Robust and Efficient Blechert-Type Cyclic(alkyl)(amino)carbene Ruthenium Complexes for Olefin Metathesis

**Permalink**

https://escholarship.org/uc/item/9qs4k4sk

**Journal**

ACS Catalysis, 13(9)

**ISSN**

2155-5435

**Authors**

Del Vecchio, Antonio
Talcik, Jakub
Colombel-Rouen, Sophie
et al.

**Publication Date**

2023-05-05

**DOI**

10.1021/acscatal.3c01208

**Copyright Information**

This work is made available under the terms of a Creative Commons Attribution License, available at https://creativecommons.org/licenses/by/4.0/

Peer reviewed
**Title**

Highly Robust and Efficient Blechert-Type Cyclic(alkyl)(amino)carbene Ruthenium Complexes for Olefin Metathesis

**Permalink**

https://escholarship.org/uc/item/9qs4k4sk

**Journal**

ACS Catalysis, 13(9)

**ISSN**

2155-5435

**Authors**

Del Vecchio, Antonio
Talcik, Jakub
Colombel-Rouen, Sophie
et al.

**Publication Date**

2023-05-05

**DOI**

10.1021/acscatal.3c01208

**Copyright Information**

This work is made available under the terms of a Creative Commons Attribution License, available at https://creativecommons.org/licenses/by/4.0/

Peer reviewed
# Highly Robust and Efficient Blechert-type Cyclic(alkyl)(amino)carbene Ruthenium Complexes for Olefin Metathesis †.

Antonio Del Vecchio,ª Jakub Talcik,ª Sophie Colombel-Rouen,ª Jan Lorkowski,ª Melinda R. Serrato,ᵇ Thierry Roisnel,ª Nicolas Vanthuyne,ᶜ Guy Bertrand,*b Rodolphe Jazzar*b and Marc Mauduit*a

a. Univ de Rennes, École Nationale Supérieure de Chimie de Rennes, CNRS, ISCR UMR 6226, F-35000 Rennes, France;

b. UCSD-CNRS Joint Research Chemistry Laboratory (IRL 3555), Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0358, United States;

c. Aix Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France.

**ABSTRACT:** The first Blechert-type ruthenium complexes containing cyclic(alkyl)(amino)carbene (CAAC) ligands are reported. These catalysts demonstrate remarkable thermal stability in solution and excellent catalytic performances at low catalytic loading (up to 0.005 mol%) in ring-closing metathesis (RCM), macro-RCM, ring-closing enyne metathesis (RCEYM), cross-metathesis (CM), ethenolysis and ring-opening cross metathesis (ROCM). Moreover, up to 95% ee was obtained in asymmetric ring-opening cross metathesis (AROCM) and 57% ee asymmetric cross-metathesis (ACM)

## INTRODUCTION

Olefin metathesis represents a highly versatile synthetic tool to build a plethora of valuable building blocks and organic compounds.¹,² Thanks to the development of bench stable and well-defined ruthenium-arylidene complexes, this catalytic reaction is intensively used in polymer chemistry³,⁴ and fine chemistry⁵, and has also found applications in the valorisation of biomasses⁶ and the depolymerisation of polyethylene.⁷ Despite these remarkable achievements, the quest for more efficient Ru-complexes remains a very active research topic across academia and industry.¹,² A significant breakthrough was accomplished in 2007 when it was reported that the use of cyclic(alkyl)(amino)carbene (CAAC) ligands⁸⁻¹⁵ could provide very active catalysts for the ethenolysis of vegetable oils (0.0001 mol% **Ru-1**; TON up to 390.000).¹⁶,¹⁷ This peculiar behaviour, surpassing state-of-the art N-heterocyclic carbene (NHC) analogues,¹⁸ was shown to result from the improved stability of the corresponding Ru-methylidene intermediate; imparting resilience toward bimolecular decomposition.¹⁹⁻²¹ Obviously, structural modifications of the CAAC ligand framework was thoroughly investigated which led to a number of new CAAC Ru-complexes (**Ru-2-7**; Figure 1, A),²²⁻²⁸ including optically pure congeners **Ru*-8** recently developed by our groups.²⁹⁻³¹ Based on a benchmark reaction (i.e. RCM of diallyldiethylmalonate **1a**; DEDAM, see table 1) a map of structural-activity relationship (SAR) allowed to highlight two key features: i) bulky ortho-*N*-aryl substituents such as 2,6-diisopropylphenyl (DIPP) have a detrimental effect on the catalyst activity; ii) introduction of NO₂ on the labile styrenylether ligand improves reaction times.

<figure><img src="image_2.png" /><figcaption>B. Blechert-type CAAC-Ru catalysts (this work)</figcaption></figure>

<figure><img src="image_3.png" /><figcaption>**Figure 1** (A) Previously developed CAAC-Ru complexes. (B) Blechert-type CAAC-Ru complexes (this work).</figcaption></figure>
# Highly Robust and Efficient Blechert-type Cyclic(alkyl)(amino)carbene Ruthenium Complexes for Olefin Metathesis †.

Antonio Del Vecchio,ª Jakub Talcik,ª Sophie Colombel-Rouen,ª Jan Lorkowski,ª Melinda R. Serrato,ᵇ Thierry Roisnel,ª Nicolas Vanthuyne,ᶜ Guy Bertrand,\*ᵇ Rodolphe Jazzar\*ᵇ and Marc Mauduit\*ª

a. Univ de Rennes, École Nationale Supérieure de Chimie de Rennes, CNRS, ISCR UMR 6226, F-35000 Rennes, France;

b. UCSD-CNRS Joint Research Chemistry Laboratory (IRL 3555), Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0358, United States;

c. Aix Marseille Univ., CNRS, Centrale Marseille, iSm2, Marseille, France.

**ABSTRACT:** The first Blechert-type ruthenium complexes containing cyclic(alkyl)(amino)carbene (CAAC) ligands are reported. These catalysts demonstrate remarkable thermal stability in solution and excellent catalytic performances at low catalytic loading (up to 0.005 mol%) in ring-closing metathesis (RCM), macro-RCM, ring-closing enyne metathesis (RCEYM), cross-metathesis (CM), ethenolysis and ring-opening cross metathesis (ROCM). Moreover, up to 95% ee was obtained in asymmetric ring-opening cross metathesis (AROCM) and 57% ee asymmetric cross-metathesis (ACM)

## INTRODUCTION

Olefin metathesis represents a highly versatile synthetic tool to build a plethora of valuable building blocks and organic compounds.¹,² Thanks to the development of bench stable and well-defined ruthenium-arylidene complexes, this catalytic reaction is intensively used in polymer chemistry³,⁴ and fine chemistry⁵, and has also found applications in the valorisation of biomasses⁶ and the depolymerisation of polyethylene.⁷ Despite these remarkable achievements, the quest for more efficient Ru-complexes remains a very active research topic across academia and industry.¹,² A significant breakthrough was accomplished in 2007 when it was reported that the use of cyclic(alkyl)(amino)carbene (CAAC) ligands⁸⁻¹⁵ could provide very active catalysts for the ethenolysis of vegetable oils (0.0001 mol% **Ru-1**; TON up to 390.000).¹⁶,¹⁷ This peculiar behaviour, surpassing state-of-the art N-heterocyclic carbene (NHC) analogues,¹⁸ was shown to result from the improved stability of the corresponding Ru-methylidene intermediate; imparting resilience toward bimolecular decomposition.¹⁹⁻²¹ Obviously, structural modifications of the CAAC ligand framework was thoroughly investigated which led to a number of new CAAC Ru-complexes (**Ru-2-7**; Figure 1, A),²²⁻²⁸ including optically pure congeners **Ru*-8** recently developed by our groups.²⁹⁻³¹ Based on a benchmark reaction (i.e. RCM of diallyldiethylmalonate **1a**; DEDAM, see table 1) a map of structural-activity relationship (SAR) allowed to highlight two key features: i) bulky ortho-*N*-aryl substituents such as 2,6-diisopropylphenyl (DIPP) have a detrimental effect on the catalyst activity; ii) introduction of NO₂ on the labile styrenylether ligand improves reaction times.

<figure><img src="image_3.png" /><figcaption>B. Blechert-type CAAC-Ru catalysts (this work)</figcaption></figure>

<figure><img src="image_4.png" /><figcaption>**Figure 1** (A) Previously developed CAAC-Ru complexes. (B) Blechert-type CAAC-Ru complexes (this work).</figcaption></figure>
Thus, CAAC-catalysts featuring a 2,6-diethylphenyl (DEP) *N*-substituent (DEPCAAC) and a NO₂ activating group were shown to be very effective across a broad range of olefin metathesis. transformations (Ru-2,3,4; TON of 68.000 for RCM of 1a).²²⁻²⁴ Notwithstanding these advancements, a few drawbacks in the preparation of these catalysts deserve to be considered. In marked contrast with bulkier 2,6-diisopropylphenyl *N*-substituted CAAC ligands (DIPPCAAC) which are readily accessible in good to excellent yield from 1st generation Hoveyda precursors (70-91%), DEPCAAC appears to be more challenging with yields (when reported) range from 15 to 45%.³² This problem extends to nitro-Grela derivatives which are isolated in poor to moderate yields (14 to 50%).³² Given importance of CAAC-Ru complexes for the industrial sector, we investigated the preparation of Blechert-type Ru-complexes **Ru-9** (Figure 1, B).³³,³⁴ Herein we disclose a new class of CAAC catalysts readily accessible from the commercially available Grubbs 1st generation complex **GI**³⁵ in good yields (Scheme 1, Eq. 2). These catalysts demonstrate remarkable catalytic activity (as low as 0.001 mol%) towards a wide range of metathesis transformations. Moreover, up to 95% enantioselectivity could be obtained in asymmetric olefin metathesis with only 0.05 mol% of optically pure **Ru-9**.

## RESULTS AND DISCUSSION

We initiated our study by attempting the preparation of DIPPCAAC **Ru-9** complexes starting from the phosphine-based Blechert precursor **BI** (Scheme 1, Eq. 1).³⁶ Unfortunately, in this case only trace amount of DIPPCAAC **Ru-9a** was observed (<3%) which we attributed to the relative instability of **BI** in solution. In contrast, deprotonation of **C1a·BF₄** with potassium hexamethyldisilazide (KHMDS) in presence of **Pyr-GI**,¹⁶ afforded the expected DIPPCAAC **Ru-9a** in 45% yield (over two step) on gram-scale.

<figure><img src="image_4.png" /><figcaption>**Scheme 1** Synthesis of Blechert-type CAAC Ru-9a-c. a Isolated yield over 2 steps.</figcaption></figure>

<figure><img src="image_5.png" /><figcaption>**Figure 2** Solid-state structure of complexes **Ru-9a,b,c** from single crystal X-ray diffraction. Displacement ellipsoids are drawn at 30% probability. Hydrogen atoms have been omitted for clarity.</figcaption></figure>

It is worth mentioning that **Pyr-GI** is readily accessible from the first-generation **GI** complex in the presence of pyridine (>90% yield, Scheme 1, Eq. 2).³⁷ Similarly, DIPPCAAC-Blechert complexes, bearing a spirocyclohexyl (**Ru-9b**) and methyl/cyclohexyl (**Ru-9c**) at the quaternary centre were isolated in 34 and 70% yield, respectively. We confirmed the structure of **Ru-9a,b,c** by X-ray diffraction analysis (Figure 2).³⁸,³⁹ Blechert-type NHC-catalysts often lack stability in solution.³⁸ As shown in Figure 3, DIPPCAAC-Blechert **Ru-9a** demonstrated a remarkable stability in presence of air at 80 °C in toluene-d₈ (0.1 M), with up to 52% remaining complex after seven days and a complete decomposition over 28 days (see Figure 3 and Supporting Information (SI) for details). Of note is that the SIPr-Blechert analogue **BII** (*vide infra*, table 1, entry 8) showed a lower stability with only 80% remaining complex after 3.5 hours and a full decomposition after 3.5 days (see SI for details).

<figure><img src="image_6.png" /><figcaption>**Figure 3** Thermal stability of DIPPCAAC-Blechert **Ru-9a** (blue) and SIPr-Blechert **BII** (red) in toluene-d₈ (0.1M) at 80 °C. Pre-catalyst decomposition was monitored by ¹H-NMR spectroscopy with 1,3,5-trimethoxybenzene as internal standard.</figcaption></figure>

Having confirmed the stability of these catalysts, we next investigated their catalytic performances of Blechert-CAAC **Ru-9a,b,c** in the RCM of DEDAM **1a** (Table 1). At 0.1 mol% catalyst loading DIPPCAAC **Ru-9b,c** showed a poor reactivity (5-10% conv., entries 3,5, after 2h) comparable to that of nitro-Grela DIPPCAAC **Ru-3a,b** (entries 1-2).⁴⁰ As expected, higher catalyst concentration led to nearly full conversions (entries 4,6). To our surprise **Ru-9a** displaying bearing Me/Ph substituents at the quaternary centre showed significantly higher
Thus, CAAC-catalysts featuring a 2,6-diethylphenyl (DEP) N-substituent (DEPCAAC) and a NO₂ activating group were shown to be very effective across a broad range of olefin metathesis. transformations (Ru-2,3,4; TON of 68.000 for RCM of 1a).²²⁻²⁴ Notwithstanding these advancements, a few drawbacks in the preparation of these catalysts deserve to be considered. In marked contrast with bulkier 2,6-diisopropylphenyl N-substituted CAAC ligands (DIPPCAAC) which are readily accessible in good to excellent yield from 1st generation Hoveyda precursors (70-91%), DEPCAAC appears to be more challenging with yields (when reported) range from 15 to 45%.³² This problem extends to nitro-Grela derivatives which are isolated in poor to moderate yields (14 to 50%).³² Given importance of CAAC-Ru complexes for the industrial sector, we investigated the preparation of Blechert-type Ru-complexes **Ru-9** (Figure 1, B).³³,³⁴ Herein we disclose a new class of CAAC catalysts readily accessible from the commercially available Grubbs 1st generation complex **GI**³⁵ in good yields (Scheme 1, Eq. 2). These catalysts demonstrate remarkable catalytic activity (as low as 0.001 mol%) towards a wide range of metathesis transformations. Moreover, up to 95% enantioselectivity could be obtained in asymmetric olefin metathesis with only 0.05 mol% of optically pure **Ru-9**.

## RESULTS AND DISCUSSION

We initiated our study by attempting the preparation of DIPPCAAC **Ru-9** complexes starting from the phosphine-based Blechert precursor **BI** (Scheme 1, Eq. 1).³⁶ Unfortunately, in this case only trace amount of DIPPCAAC **Ru-9a** was observed (<3%) which we attributed to the relative instability of **BI** in solution. In contrast, deprotonation of **C1a·BF₄** with potassium hexamethyldisilazide (KHMDS) in presence of **Pyr-GI**,¹⁶ afforded the expected DIPPCAAC **Ru-9a** in 45% yield (over two step) on gram-scale.

<figure><img src="image_5.png" /><figcaption>**Scheme 1** Synthesis of Blechert-type CAAC Ru-9a-c. a Isolated yield over 2 steps.</figcaption></figure>

<figure><img src="image_6.png" /><figcaption>**Figure 2** Solid-state structure of complexes **Ru-9a,b,c** from single crystal X-ray diffraction. Displacement ellipsoids are drawn at 30% probability. Hydrogen atoms have been omitted for clarity.</figcaption></figure>

It is worth mentioning that **Pyr-GI** is readily accessible from the first-generation **GI** complex in the presence of pyridine (>90% yield, Scheme 1, Eq. 2).³⁷ Similarly, DIPPCAAC-Blechert complexes, bearing a spirocyclohexyl (**Ru-9b**) and methyl/cyclohexyl (**Ru-9c**) at the quaternary centre were isolated in 34 and 70% yield, respectively. We confirmed the structure of **Ru-9a,b,c** by X-ray diffraction analysis (Figure 2).³⁸,³⁹ Blechert-type NHC-catalysts often lack stability in solution.³⁸ As shown in Figure 3, DIPPCAAC-Blechert **Ru-9a** demonstrated a remarkable stability in presence of air at 80 °C in toluene-d₈ (0.1 M), with up to 52% remaining complex after seven days and a complete decomposition over 28 days (see Figure 3 and Supporting Information (SI) for details). Of note is that the SIPr-Blechert analogue **BII** (*vide infra*, table 1, entry 8) showed a lower stability with only 80% remaining complex after 3.5 hours and a full decomposition after 3.5 days (see SI for details).

<figure><img src="image_7.png" /><figcaption>**Figure 3** Thermal stability of DIPPCAAC-Blechert **Ru-9a** (blue) and SIPr-Blechert **BII** (red) in toluene-d₈ (0.1M) at 80 °C. Pre-catalyst decomposition was monitored by ¹H-NMR spectroscopy with 1,3,5-trimethoxybenzene as internal standard.</figcaption></figure>

Having confirmed the stability of these catalysts, we next investigated their catalytic performances of Blechert-CAAC **Ru-9a,b,c** in the RCM of DEDAM **1a** (Table 1). At 0.1 mol% catalyst loading DIPPCAAC **Ru-9b,c** showed a poor reactivity (5-10% conv., entries 3,5, after 2h) comparable to that of nitro-Grela DIPPCAAC **Ru-3a,b** (entries 1-2).⁴⁰ As expected, higher catalyst concentration led to nearly full conversions (entries 4,6). To our surprise **Ru-9a** displaying bearing Me/Ph substituents at the quaternary centre showed significantly higher
reactivity within 2 hours at 0.1 mol%, affording the desired cyclopentene **2a** in 97% yield after 2 hours at 0.1 mol% loading, thus surpassing the SIPr-Blechert **BII** (entry 7 vs 8). More interestingly, **Ru-9a** remains active at lower catalyst concentrations reaching up to 17.000 TON with 0.005 mol% catalyst loading (entries 9-13). Note that under these conditions a 20-fold higher solvent concentration (2 M) was required to improve the mass transfer (entry 10 vs 11).41,42

<figure><img src="image_7.png" /><figcaption>**Table 1** Catalytic performances of Blechert-type CAAC **Ru-9a-c** in ring-closing metathesis of DEDAM **1a** and comparison with nitro-Grela congeners **Ru-3a,b** and SIPr-Blechert **BII**.</figcaption></figure>

<table><thead><tr><th>Entry</th><th>Catalyst</th><th>Mol%</th><th>Time (h)</th><th>Conv./Yield (%)<sup>a</sup></th></tr></thead><tbody><tr><td>1</td><td>Ru-3a</td><td>0.1</td><td>1</td><td>10 ref. 21</td></tr><tr><td>2</td><td>Ru-3b</td><td>0.1</td><td>1</td><td>5 ref. 21</td></tr><tr><td>3</td><td>Ru-9b</td><td>0.1</td><td>2</td><td>4 (4)</td></tr><tr><td>4</td><td>Ru-9b</td><td>1</td><td>2</td><td>99 (96)</td></tr><tr><td>5</td><td>Ru-9c</td><td>0.1</td><td>2</td><td>7 (7)</td></tr><tr><td>6</td><td>Ru-9c</td><td>1</td><td>2</td><td>83 (72)</td></tr><tr><td>7</td><td>Ru-9a</td><td>0.1</td><td>2</td><td>99 (97)</td></tr><tr><td>8</td><td>BII</td><td>0.1</td><td>4</td><td>75 (73)</td></tr><tr><td>9</td><td>Ru-9a</td><td>0.05</td><td>4</td><td>99 (96)</td></tr><tr><td>10</td><td>Ru-9a</td><td>0.01</td><td>4</td><td>50 (48)</td></tr><tr><td>11<sup>b</sup></td><td>Ru-9a</td><td>0.01</td><td>4</td><td>96 (94)</td></tr><tr><td>12<sup>b,c</sup></td><td>Ru-9a</td><td>0.005</td><td>4</td><td>90 (85)</td></tr><tr><td>13<sup>b,c</sup></td><td>Ru-9a</td><td>0.0025</td><td>4</td><td>23 (12)</td></tr></tbody></table>

<sup>a</sup> Determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard (see SI). <sup>b</sup> Toluene (2 M). <sup>c</sup> Reaction performed at 40 °C.

Having identified Blechert DIPPCAAC **Ru-9a** as the most efficient catalyst, we then investigated its performances in various olefin metathesis transformations at 0.1 to 0.5 mol%. In ring-closing metathesis (Scheme 2, a), full conversions and good to excellent yields (86-98%) were obtained for the formation of di- or tri-substituted cyclopentenes **2a,b,d,e**. Unfortunately, no reaction was obtained with the more challenging tetrasubstituted cyclopentenes **2c** and **2f**. To our delight, seven-membered rings were also formed in good yields (**2g,h,i**: 71-95%), while cyclic silanes **2j** and **2k** were obtained in low to moderate yields (17-38%). We also considered ring-closing enyne metathesis (RCEYM), in which DIPPCAAC **Ru-9a** showed good activity at 0.1-0.5 mol%, affording **4a,b** in 93-98% yield respectively (Scheme 2, b). However, lower conversions (26-30%) were observed for products **4c,d** despite the use of more drastic conditions.

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(no reaction)

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(no reaction)

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9 (4 equiv)

Ru-9a (0.5 mol%)

Toluene (0.1 M)
80 °C, 4 h

<figure><img src="image_52.png" /></figure>

<figure><img src="image_53.png" /></figure>

[on 1 mol% (84%)]<sup>g</sup>

**Scheme 2** Scope of RCM (a), RCEYM (b) and ROCM (c,d) catalyzed by Blechert-CAAC **Ru-9a** complex. <sup>a</sup> Conversions were determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard. <sup>b</sup> NMR yield. <sup>c</sup> Reaction performed at 80 °C. <sup>d</sup> E/Z ratio were monitored by ¹H NMR analysis.
reactivity within 2 hours at 0.1 mol%, affording the desired cyclopentene **2a** in 97% yield after 2 hours at 0.1 mol% loading, thus surpassing the SIPr-Blechert **BII** (entry 7 vs 8). More interestingly, **Ru-9a** remains active at lower catalyst concentrations reaching up to 17.000 TON with 0.005 mol% catalyst loading (entries 9-13). Note that under these conditions a 20-fold higher solvent concentration (2 M) was required to improve the mass transfer (entry 10 vs 11).<sup>41,42</sup>

<figure><img src="image_8.png" /><figcaption>**Table 1** Catalytic performances of Blechert-type CAAC **Ru-9a-c** in ring-closing metathesis of DEDAM **1a** and comparison with nitro-Grela congeners **Ru-3a,b** and SIPr-Blechert **BII**.</figcaption></figure>

<table><thead><tr><th>Entry</th><th>Catalyst</th><th>Mol%</th><th>Time (h)</th><th>Conv./Yield (%)<sup>a</sup></th></tr></thead><tbody><tr><td>1</td><td>Ru-3a</td><td>0.1</td><td>1</td><td>10 ref. 21</td></tr><tr><td>2</td><td>Ru-3b</td><td>0.1</td><td>1</td><td>5 ref. 21</td></tr><tr><td>3</td><td>Ru-9b</td><td>0.1</td><td>2</td><td>4 (4)</td></tr><tr><td>4</td><td>Ru-9b</td><td>1</td><td>2</td><td>99 (96)</td></tr><tr><td>5</td><td>Ru-9c</td><td>0.1</td><td>2</td><td>7 (7)</td></tr><tr><td>6</td><td>Ru-9c</td><td>1</td><td>2</td><td>83 (72)</td></tr><tr><td>7</td><td>Ru-9a</td><td>0.1</td><td>2</td><td>99 (97)</td></tr><tr><td>8</td><td>BII</td><td>0.1</td><td>4</td><td>75 (73)</td></tr><tr><td>9</td><td>Ru-9a</td><td>0.05</td><td>4</td><td>99 (96)</td></tr><tr><td>10</td><td>Ru-9a</td><td>0.01</td><td>4</td><td>50 (48)</td></tr><tr><td>11<sup>b</sup></td><td>Ru-9a</td><td>0.01</td><td>4</td><td>96 (94)</td></tr><tr><td>12<sup>b,c</sup></td><td>Ru-9a</td><td>0.005</td><td>4</td><td>90 (85)</td></tr><tr><td>13<sup>b,c</sup></td><td>Ru-9a</td><td>0.0025</td><td>4</td><td>23 (12)</td></tr></tbody></table>

Having identified Blechert DIPPCAAC **Ru-9a** as the most efficient catalyst, we then investigated its performances in various olefin metathesis transformations at 0.1 to 0.5 mol%. In ring-closing metathesis (Scheme 2, a), full conversions and good to excellent yields (86-98%) were obtained for the formation of di- or tri-substituted cyclopentenes **2a,b,d,e**. Unfortunately, no reaction was obtained with the more challenging tetrasubstituted cyclopentenes **2c** and **2f**. To our delight, seven-membered rings were also formed in good yields (**2g,h,i**: 71-95%), while cyclic silanes **2j** and **2k** were obtained in low to moderate yields (17-38%). We also considered ring-closing enyne metathesis (RCEYM), in which DIPPCAAC **Ru-9a** showed good activity at 0.1-0.5 mol%, affording **4a,b** in 93-98% yield respectively (Scheme 2, b). However, lower conversions (26-30%) were observed for products **4c,d** despite the use of more drastic conditions.

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(no reaction)

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9 (4 equiv)

Ru-9a (0.5 mol%)

Toluene (0.1 M)
80 °C, 4 h

<figure><img src="image_54.png" /></figure>

98% conv.<sup>a</sup> (38%)<sup>b</sup>
8:2 E:Z ratio<sup>d</sup>

[on 1 mol% (84%)<sup>b</sup>]</td></tr></tbody></table>

**Scheme 2** Scope of RCM (a), RCEYM (b) and ROCM (c,d) catalyzed by Blechert-CAAC **Ru-9a** complex. <sup>a</sup> Conversions were determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard. <sup>b</sup> NMR yield. <sup>c</sup> Reaction performed at 80 °C. <sup>d</sup> E/Z ratio were monitored by ¹H NMR analysis.

<footnote><sup>a</sup> Determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard (see SI). <sup>b</sup> Toluene (2 M). <sup>c</sup> Reaction performed at 40 °C.</footnote>
We next considered the ring-opening cross-metathesis (ROCM) of endo-norbornenes 5a,b and exo-norbornenes 7a,b with styrene which afforded the corresponding cis-cyclopentanes 6a,b and trans-cyclopentanes 8a,b in moderate to good yield (41-79%) and a 8:2 E:Z ratio (Scheme 2, c). In contrast, ROCM of endo-5b with allyl acetate gave the expected cis-cyclopentane 6c in 87% yield and a similar 8:2 E:Z ratio. Finally, the ROCM between cyclooctene 9 and cis-1,4-diacetoxy-2-butene 10 furnished the corresponding linear diene 11 with a modest 38% yield (Scheme 2, d). Fortunately, the latter can be improved reaching 84% with 1 mol% catalyst loading. It is worth mentioning that all ROCM transformations required thermal activation (80 °C).

Shifting our investigation to cross-metathesis (CM) with various cross-olefin partners (Scheme 3), we found that the reaction between allyl acetate 12 and 1-nonene or 1-dodecene led to the expected linear alkenes 13a,b in 43 and 58% isolated yield with a 75:25 and 8:2 E:Z ratio, respectively (Scheme 3). A similar 52% yield and E:Z ratio was observed for product 13c resulting from the CM with homoallyl benzene. Replacing allyl acetate 12 with cis-1,4-diacetoxy-2-butene 10 slightly improved the isolated yields irrespectively of cross-olefin partners (62-75%).

<figure><img src="image_54.png" /><figcaption>**Scheme 3** Scope of CM catalyzed by Blechert-CAAC **Ru-9a** complex. a Isolated yield. b E/Z ratio were monitored by ¹H NMR analysis. c 1 mol% of catalyst was used.</figcaption></figure>

We also examined the cross-metathesis between the methyl ester of oleic acid 14 and ethylene (also called ethenolysis;). The reaction was performed under 1 bar of ethylene in presence of 0.1-0.0005 mol% of **Ru-9a** (Table 2). We were delighted to obtain a 97% yield for the expected methyl 1-decenuate 15 and 1-decene 16 after 3 hours at 80 °C in toluene (entry 1). Importantly, despite the use of low pressure of ethylene gas, no trace of self-metathesis products was detected by GC (see SI for details), showcasing once again the remarkable selectivity of CAAC-based Ru catalysts for this transformation.¹⁷ In order to increase the TON, we performed the reaction at lower catalyst loading (0.01 mol%) but a poor 7% yield was observed (entry 2).

<figure><img src="image_55.png" /><figcaption>**Table 2** Low-pressure ethenolysis of methyloleate 14 catalyzed by Blechert-CAAC **Ru-9a** complex.</figcaption></figure>

a Determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard (see SI). b Reaction performed at 10 bar, 40 °C.

In neat conditions, the reactivity was improved affording 15 and 16 in 36% yield (TON 3600, entry 3). Noteworthy, a large amount of methyl elaidate – the *E* isomer of the starting material resulting from the reverse cross-metathesis – was also detected (see SI for details). Finally, the best TON (16000) was achieved at 0.0005 mol% (without any detection of methyl elaidate). The use of higher pressure (10 bar) did not lead to any improvement (entry 5 vs 6).

At last, we focused our attention toward macrocyclic ring-closing metathesis (macro-RCM) which is used in the production of macrocyclic odorant molecules frequently used in perfumery for their strong musk fragrance.⁴³,⁴⁴

<figure><img src="image_56.png" /><figcaption>**Table 3** Catalytic performances of Blechert-CAAC **Ru-9a** in macro-RCM of hex-5-enyl undec-10-enoate 17a furnishing 16-membered Exaltolide precursor 18a.</figcaption></figure>

a Conversions and yields were determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard. b E/Z ratio: 7/3 (determined by GC analysis). c Determined by GC analysis (see SI for details). d Isolated yield after SiO₂ purification.
We next considered the ring-opening cross-metathesis (ROCM) of endo-norbornenes 5a,b and exo-norbornenes 7a,b with styrene which afforded the corresponding cis-cyclopentanes 6a,b and trans-cyclopentanes 8a,b in moderate to good yield (41-79%) and a 8:2 E:Z ratio (Scheme 2, c). In contrast, ROCM of endo-5b with allyl acetate gave the expected cis-cyclopentane 6c in 87% yield and a similar 8:2 E:Z ratio. Finally, the ROCM between cyclooctene 9 and cis-1,4-diacetoxy-2-butene 10 furnished the corresponding linear diene 11 with a modest 38% yield (Scheme 2, d). Fortunately, the latter can be improved reaching 84% with 1 mol% catalyst loading. It is worth mentioning that all ROCM transformations required thermal activation (80 °C).

Shifting our investigation to cross-metathesis (CM) with various cross-olefin partners (Scheme 3), we found that the reaction between allyl acetate 12 and 1-nonene or 1-dodecene led to the expected linear alkenes 13a,b in 43 and 58% isolated yield with a 75:25 and 8:2 E:Z ratio, respectively (Scheme 3). A similar 52% yield and E:Z ratio was observed for product 13c resulting from the CM with homoallyl benzene. Replacing allyl acetate 12 with cis-1,4-diacetoxy-2-butene 10 slightly improved the isolated yields irrespectively of cross-olefin partners (62-75%).

<figure><img src="image_55.png" /><figcaption>**Scheme 3** Scope of CM catalyzed by Blechert-CAAC **Ru-9a** complex. a Isolated yield. b E/Z ratio were monitored by ¹H NMR analysis. c 1 mol% of catalyst was used.</figcaption></figure>

We also examined the cross-metathesis between the methyl ester of oleic acid 14 and ethylene (also called ethenolysis;). The reaction was performed under 1 bar of ethylene in presence of 0.1-0.0005 mol% of **Ru-9a** (Table 2). We were delighted to obtain a 97% yield for the expected methyl 1-decenoate 15 and 1-decene 16 after 3 hours at 80 °C in toluene (entry 1). Importantly, despite the use of low pressure of ethylene gas, no trace of self-metathesis products was detected by GC (see SI for details), showcasing once again the remarkable selectivity of CAAC-based Ru catalysts for this transformation.¹⁷ In order to increase the TON, we performed the reaction at lower catalyst loading (0.01 mol%) but a poor 7% yield was observed (entry 2).

<figure><img src="image_56.png" /><figcaption>**Table 2** Low-pressure ethenolysis of methyloleate 14 catalyzed by Blechert-CAAC **Ru-9a** complex.</figcaption></figure>

a Determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard (see SI). b Reaction performed at 10 bar, 40 °C.

In neat conditions, the reactivity was improved affording 15 and 16 in 36% yield (TON 3600, entry 3). Noteworthy, a large amount of methyl elaidate – the *E* isomer of the starting material resulting from the reverse cross-metathesis – was also detected (see SI for details). Finally, the best TON (16000) was achieved at 0.0005 mol% (without any detection of methyl elaidate). The use of higher pressure (10 bar) did not lead to any improvement (entry 5 vs 6).

At last, we focused our attention toward macrocyclic ring-closing metathesis (macro-RCM) which is used in the production of macrocyclic odorant molecules frequently used in perfumery for their strong musk fragrance.⁴³,⁴⁴

<figure><img src="image_57.png" /><figcaption>**Table 3** Catalytic performances of Blechert-CAAC **Ru-9a** in macro-RCM of hex-5-enyl undec-10-enoate 17a furnishing 16-membered Exaltolide precursor 18a.</figcaption></figure>

a Conversions and yields were determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard. b E/Z ratio: 7/3 (determined by GC analysis). c Determined by GC analysis (see SI for details). d Isolated yield after SiO₂ purification.
We first investigated the catalytic performance of Blechert DIPPCAAC **Ru-9a** (0.1 mol%, 5 mM in toluene, Table 3, entry 1) in the cyclisation of hex-5-enyl undec-10-enoate **17a**. In this case, the resulting 16-membered macrocycle **18a** –a precursor of Exaltolide⁴⁵– was obtained in a *E/Z* mixture (7/3 ratio) and 87% isolated yield after silica gel purification. Noteworthy, **21b** showed an excellent purity (>99%) with no by-products (i.e. ring-contraction resulting from isomerisation of starting material)⁴⁶⁻⁴⁹ detected by GC. Interestingly, a similar 87% yield and >99% purity was obtained at lower dilution (10 mM) and catalyst loading (0.05 mol%; entry 2). Attempts to decrease the latter to 0.01 mol% resulted in a significant drop of conversion/yield (55%; entry 3), meanwhile increasing reaction concentration (up to 100 mM) improve the yield significantly (entries 5-6).⁵⁰ To extend the scope of mRCM, we also considered a range of macrocyclic lactones and ketones (Scheme 4). Under optimal conditions (5 to 10 mM, 0.5 mol% of **Ru-9a**, 80 °C, 6 h), we were delighted to observe that the 15-membered lactone **18b** could be formed in high 88% NMR yield with an excellent >99% purity and a 4/6 *E/Z* ratio. Unexpectedly, purification of **18b** by chromatography separation proved challenging and resulted in a lower yield than anticipated (63%). Similarly, 17-membered lactone **18c** (namely *iso-ambrettolide*)⁵¹ was also isolated in lower yield (isolated: 46%; NMR: 84%).

<figure><img src="image_57.png" /></figure>

**Scheme 4** Scope of macrocyclic RCM of dienic substrates **17b-e** catalyzed by Blechert-CAAC **Ru-9a** complex leading to the corresponding macrocyclic **21b-e**. <sup>a</sup> Determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard. <sup>b</sup> Isolated yields after SiO<sub>2</sub> purification. <sup>c</sup> Determined by GC analysis (see SI for details). <sup>d</sup>*E/Z* ratio: 4/6. <sup>e</sup>*E/Z* ratio: 8/2. <sup>f</sup>*E/Z* ratio: 7/3. <sup>g</sup>*E/Z* ratio: 7/3.

Here also, no trace of by-products was detected (purity >99%). Using the 17-membered macrocyclic ketone **18d** (namely Civetone),⁵²⁻⁵⁴ up to 81% NMR yield was obtained (61% isolated yield) while its 18-membered analogue **18e**⁵⁵ was formed in lower yield (isolated: 47%; NMR: 65%). Of note, Blechert DIPPCAAC **Ru-9a** did not afford the 13-membered lactone and 15-membered macrocyclic carbamate under these conditions.

Having recently disclosed the catalytic activity of chiral CAACs (ChiCAACs) in asymmetric olefin metathesis,²⁹⁻³¹,⁵⁶ we also considered the enantiopure variant of DIPPCAAC **Ru-9a** for the same. Both enantiomers were isolated in good yields and excellent enantiomeric purity (up to >99.5 ee%) by preparative HPLC resolution (see SI for details). In the AROCM³⁶,⁵⁷⁻⁶¹ between endonorbornene **5a** and styrene (Scheme 5, a), the expected *cis*-cyclopentane **6a** was isolated in 44% yield and an excellent 95% ee using 2 mol% of (*R*)-(*+*)-**Ru-9a**. In contrast, larger catalyst loading (5 mol%), longer reaction time (48h) and higher temperature were required to reach similar nitro-DIPPCAAC (*R*)-(*+*)-**Ru-1a**. To our delight, the chiral Blechert catalyst remained highly performant even at lower catalyst loading (0.5 mol%), affording **6a** in 86% ee. More interestingly, (*R*)-(*+*)-**Ru-9a** catalysed the AROCM of *exo*-norbornene **7b** with only 0.05 mol% leading to the corresponding *trans*-cyclopentane **8b** in 51% yield and up to 93% ee (Scheme 5, b).

<figure><img src="image_58.png" /></figure>

**Scheme 5** Asymmetric olefin metathesis catalyzed by optically pure Blechert-CAAC (*R*)-(*+*)-**Ru-9a** complex.<sup>a</sup> Determined by ¹H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard.<sup>b</sup> Isolated yields after SiO<sub>2</sub> purification.<sup>c</sup> Determined by GC-MS analysis.<sup>d</sup> Determined by HPLC or GC analysis on chiral phase (see ESI for details).
We first investigated the catalytic performance of Blechert DIPPCAAC **Ru-9a** (0.1 mol%, 5 mM in toluene, Table 3, entry 1) in the cyclisation of hex-5-enyl undec-10-enoate **17a**. In this case, the resulting 16-membered macrocycle **18a** –a precursor of Exaltolide⁴⁵– was obtained in a *E/Z* mixture (7/3 ratio) and 87% isolated yield after silica gel purification. Noteworthy, **21b** showed an excellent purity (>99%) with no by-products (i.e. ring-contraction resulting from isomerisation of starting material)⁴⁶⁻⁴⁹ detected by GC. Interestingly, a similar 87% yield and >99% purity was obtained at lower dilution (10 mM) and catalyst loading (0.05 mol%; entry 2). Attempts to decrease the latter to 0.01 mol% resulted in a significant drop of conversion/yield (55%; entry 3), meanwhile increasing reaction concentration (up to 100 mM) improve the yield significantly (entries 5-6).⁵⁰ To extend the scope of mRCM, we also considered a range of macrocyclic lactones and ketones (Scheme 4). Under optimal conditions (5 to 10 mM, 0.5 mol% of **Ru-9a**, 80 °C, 6 h), we were delighted to observe that the 15-membered lactone **18b** could be formed in high 88% NMR yield with an excellent >99% purity and a 4/6 *E/Z* ratio. Unexpectedly, purification of **18b** by chromatography separation proved challenging and resulted in a lower yield than anticipated (63%). Similarly, 17-membered lactone **18c** (namely *iso-ambrettolide*)⁵¹ was also isolated in lower yield (isolated: 46%; NMR: 84%).

<figure><img src="image_58.png" /></figure>

**Scheme 4** Scope of macrocyclic RCM of dienic substrates **17b-e** catalyzed by Blechert-CAAC **Ru-9a** complex leading to the corresponding macrocyclic **21b-e**. <sup>a</sup> Determined by <sup>1</sup>H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard. <sup>b</sup> Isolated yields after SiO<sub>2</sub> purification. <sup>c</sup> Determined by GC analysis (see SI for details). <sup>d</sup>*E/Z* ratio: 4/6. <sup>e</sup>*E/Z* ratio: 8/2. <sup>f</sup>*E/Z* ratio: 7/3. <sup>g</sup>*E/Z* ratio: 7/3.

Here also, no trace of by-products was detected (purity >99%). Using the 17-membered macrocyclic ketone **18d** (namely Civetone),⁵²⁻⁵⁴ up to 81% NMR yield was obtained (61% isolated yield) while its 18-membered analogue **18e**⁵⁵ was formed in lower yield (isolated: 47%; NMR: 65%). Of note, Blechert DIPPCAAC **Ru-9a** did not afford the 13-membered lactone and 15-membered macrocyclic carbamate under these conditions.

Having recently disclosed the catalytic activity of chiral CAACs (ChiCAACs) in asymmetric olefin metathesis,²⁹⁻³¹,⁵⁶ we also considered the enantiopure variant of DIPPCAAC **Ru-9a** for the same. Both enantiomers were isolated in good yields and excellent enantiomeric purity (up to >99.5 ee%) by preparative HPLC resolution (see SI for details). In the AROCM³⁶,⁵⁷⁻⁶¹ between endonorbornene **5a** and styrene (Scheme 5, a), the expected *cis*-cyclopentane **6a** was isolated in 44% yield and an excellent 95% ee using 2 mol% of (*R*)-(*+*)-**Ru-9a**. In contrast, larger catalyst loading (5 mol%), longer reaction time (48h) and higher temperature were required to reach similar nitro-DIPPCAAC (*R*)-(*+*)-**Ru-1a**. To our delight, the chiral Blechert catalyst remained highly performant even at lower catalyst loading (0.5 mol%), affording **6a** in 86% ee. More interestingly, (*R*)-(*+*)-**Ru-9a** catalysed the AROCM of *exo*-norbornene **7b** with only 0.05 mol% leading to the corresponding *trans*-cyclopentane **8b** in 51% yield and up to 93% ee (Scheme 5, b).

<figure><img src="image_59.png" /></figure>

**Scheme 5** Asymmetric olefin metathesis catalyzed by optically pure Blechert-CAAC (*R*)-(*+*)-**Ru-9a** complex.<sup>a</sup> Determined by <sup>1</sup>H NMR spectroscopy using 1,3,5-trimethoxybenzene as internal standard.<sup>b</sup> Isolated yields after SiO<sub>2</sub> purification.<sup>c</sup> Determined by GC-MS analysis.<sup>d</sup> Determined by HPLC or GC analysis on chiral phase (see ESI for details).
This impressive reactivity and selectivity were also demon-
strated in the challenging asymmetric cross-metathesis
(ACM) transformation,⁶² for which the best ee reported so
far is <54%.⁴⁴ (R)-(+)-**Ru-9a** (1 mol%) efficiently catalysed
the CM between the prochiral skipped 1,4-diene **19** and al-
lyl acetate **12**, affording **20** in 42% yield and up to 57% ee
(Scheme 5, c). It is worth mentioning that these results also
surpass those of nitro-DIPPCAAC (S)-(+)-**Ru-1a** both in terms
of efficiency and selectivity (5 mol%, 50 % ee).²⁹

CONCLUSIONS

In summary, we have developed the first Blechert-type
ruthenium complexes containing a cyclic(al-
kyl)(amino)carbene ligand. DIPPCAAC **Ru-9a** featuring a
quaternary centre bearing phenyl/methyl substituents
proved to be the most robust and efficient catalyst
across a wide range of metathesis transformations and
in most cases under very low catalyst loadings (ranging
from 0.5 to 0.005 mol%). Moderate to good yields were
obtained in various RCM, ROCM, CM and ethenolysis re-
actions. Blechert-CAAC **Ru-9a** also demonstrated high
productivity toward challenging olefin macrocycliza-
tion, which delivers valuable odorant molecules with
high >99% purity. Used in asymmetric olefin metathe-
sis, chiral (R)-(+)-**Ru-9a** successfully furnished AROCM
and ACM products at low catalyst loadings (from 1 to
0.05 mol%) in 93% and 57% ee, respectively. Future
work will focus on the use of **Ru-9a** in continuous flow
conditions⁶³ as well as in relevant enantioselective me-
tathesis transformations, more specifically toward the
highly challenging asymmetric ring-closing enyne me-
tathesis (ARCEYM).⁶⁴,⁶⁵

ASSOCIATED CONTENT

Supporting Information

The Supporting Information is available free of charge on
the ACS Publications website. NMR spectra of products, GC
analyses, experimental procedures and details about DFT
calculations are provided. X-ray crystallographic data (CIF)
are available on the CCDC website.

AUTHOR INFORMATION

Corresponding Authors

**Marc Mauduit** - Univ Rennes, Ecole Nationale Supérieure de Chimie de Rennes, CNRS, ISCR UMR 6226, F-35000 Rennes, France. Email: marc.mauduit@ensc-rennes.fr.

**Rodolph Jazzar** - UCSD-CNRS Joint Research Chemistry Laboratory (IRL 3555), Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0358, United States. Email: rjazzar@ucsd.edu.

**Guy Bertrand** - UCSD-CNRS Joint Research Chemistry Laboratory (IRL 3555), Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0358, United States. Email: gbertrand@ucsd

Author Contributions

G. B., R. J. and M. M. conceived, designed and directed the pro-
ject. A. D.V., J. T., S. C.-R., J. L. and M. R.S. conducted all the ex-
periments. T. R. accomplished of X-Ray diffraction analy-
sis. The manuscript was written and reviewed by G. B., R.
J. and M. M. The ESI was written by A. D.V., J. T. and S. C.-R.

Notes

The authors declare no conflict of interest

ACKNOWLEDGMENT

We are grateful to the CNRS, the Ecole Nationale Supérieure de
Chimie de Rennes and the University of California San Diego.
This work was supported by the “prematuration program” of
CNRS (grant to J.L.), the Agence Nationale de la Recherche
(ANR-19-CE07-0017 ChiCAAC, grant to J.T.), “France Relance”
(for fellowship to A.D.V.) and the U.S. Department of Energy, Of-
fice of Science, Basic Energy Sciences, Catalysis Science Pro-
gram, under Award # DE-SC0009376. The generous gift of ru-
thenium complexes by Umicore AG & Co is gratefully acknowl-
edged. We thank P. Jéhan for HRMS analysis

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(4) Kovačić, S.; Slugovc, C. Ring-Opening Metathesis Polymerisation Derived Poly(Dicyclopentadiene) Based Materials. *Mater. Chem. Front.* **2020**, *4*, 2235–2255.

(5) Metathesis in Natural Product Synthesis: Strategies, Substrates, and Catalysts; Cossy, J.; Arseniyadis, S.; Meyer, C., Ed.; Wiley-VCH: Weinheim, Germany, 2010.

(6) Bruneau, C.; Fischmeister, C. Alkene Metathesis for Transformations of Renewables in Organometallics for Green Catalysis. In *Topics in Organometallic Chemistry*; Dixneuf, P.H.; Soulé, J. F., Ed.; Springer, 2018; Vol. 63.

(7) Wang, N. M.; Strong, G.; Dasilva, V.; Gao, L.; Huacuja, R.; Konstantinov, I. A.; Rosen, M. S.; Nett, A. J.; Ewart, S.; Geyer, R.; Scott, S. L.; Guironnet, D. Chemical Recycling of Polyethylene by Tandem Catalytic Conversion to Propylene. *J. Am. Chem. Soc.* **2022**, *144*, 18526–18531.

(8) Lavallo, V.; Canac, Y.; Präsang, C.; Donnadieu, B.; Bertrand, G. Stable Cyclic (Alkyl)(Amino)Carbenes as Rigid or Flexible, Bulky, Electron-Rich Ligands for Transition-Metal Catalysts: A Quaternary Carbon Atom Makes the Difference. *Angew. Chem. Int. Ed.* **2005**, *44*, 5705–5709.

(9) Jazzar, R.; Dewhurst, R. D.; Bourg, J. B.; Donnadieu, B.; Canac, Y.; Bertrand, G. Intramolecular "Hydroiminiumation" of Alkenes: Application to the Synthesis of Conjugate Acids of Cyclic Alkyl Amino Carbenes (CAACs). *Angew. Chem. Int. Ed.* **2007**, *46*, 2899–2902.

(10) Vermersch, F.; Oliveira, L.; Hunter, J.; Soleilhavoup, M.; Jazzar, R.; Bertrand, G. Cyclic (Alkyl)(Amino)Carbenes: Synthesis of Iminium Precursors and Structural Properties. *J. Org. Chem.* **2022**, *87*, 3511–3518.

(11) Soleilhavoup, M.; Bertrand, G. Cyclic (Alkyl)(Amino)Carbenes (CAACs): Stable Carbenes on the Rise. *Acc. Chem. Res.* **2015**, *48*, 256–266.

(12) Melaimi, M.; Jazzar, R.; Soleilhavoup, M.; Bertrand, G. Cyclic (Alkyl)(Amino)Carbenes (CAACs): Recent Developments. *Angew. Chem. Int. Ed.* **2017**, *56*, 10046–10068.

(13) Philipp, M. S. M.; Krahfuss, M. J.; Radacki, K.; Radius, U. N- Heterocyclic Carbene and Cyclic (Alkyl)(Amino)Carbene Adducts of Antimony(III). *Eur. J. Inorg. Chem.* **2021**, *2021*, 4007–4019.

(14) Jazzar, R.; Soleilhavoup, M.; Bertrand, G. Cyclic (Alkyl)- And (Aryl)- (Amino)Carbene Coinage Metal Complexes and Their
This impressive reactivity and selectivity were also demon-
strated in the challenging asymmetric cross-metathesis
(ACM) transformation,⁶² for which the best ee reported so
far is <54%.⁴⁴ (R)-(+)-**Ru-9a** (1 mol%) efficiently catalysed
the CM between the prochiral skipped 1,4-diene **19** and al-
lyl acetate **12**, affording **20** in 42% yield and up to 57% ee
(Scheme 5, c). It is worth mentioning that these results also
surpass those of nitro-DIPPCAAC (S)-(+)-**Ru-1a** both in terms
of efficiency and selectivity (5 mol%, 50 % ee).²⁹

CONCLUSIONS

In summary, we have developed the first Blechert-type
ruthenium complexes containing a cyclic(al-
kyl)(amino)carbene ligand. DIPPCAAC **Ru-9a** featuring a
quaternary centre bearing phenyl/methyl substituents
proved to be the most robust and efficient catalyst
across a wide range of metathesis transformations and
in most cases under very low catalyst loadings (ranging
from 0.5 to 0.005 mol%). Moderate to good yields were
obtained in various RCM, ROCM, CM and ethenolysis re-
actions. Blechert-CAAC **Ru-9a** also demonstrated high
productivity toward challenging olefin macrocycliza-
tion, which delivers valuable odorant molecules with
high >99% purity. Used in asymmetric olefin metathe-
sis, chiral (R)-(+)-**Ru-9a** successfully furnished AROCM
and ACM products at low catalyst loadings (from 1 to
0.05 mol%) in 93% and 57% ee, respectively. Future
work will focus on the use of **Ru-9a** in continuous flow
conditions⁶³ as well as in relevant enantioselective me-
tathesis transformations, more specifically toward the
highly challenging asymmetric ring-closing enyne me-
tathesis (ARCEYM).⁶⁴,⁶⁵

ASSOCIATED CONTENT

**Supporting Information**

The Supporting Information is available free of charge on
the ACS Publications website. NMR spectra of products, GC
analyses, experimental procedures and details about DFT
calculations are provided. X-ray crystallographic data (CIF)
are available on the CCDC website.

AUTHOR INFORMATION

Corresponding Authors

**Marc Mauduit** - Univ Rennes, Ecole Nationale Supérieure de Chimie de Rennes, CNRS, ISCR UMR 6226, F-35000 Rennes, France. Email: marc.mauduit@ensc-rennes.fr.

**Rodolph Jazzar** - UCSD-CNRS Joint Research Chemistry Laboratory (IRL 3555), Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0358, United States. Email: rjazzar@ucsd.edu.

**Guy Bertrand** - UCSD-CNRS Joint Research Chemistry Laboratory (IRL 3555), Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, California 92093-0358, United States. Email: gbertrand@ucsd

Author Contributions

G. B., R. J. and M. M. conceived, designed and directed the pro-
ject. A. D.V., J. T., S. C.-R., J. L. and M. R.S. conducted all the ex-
periments. T. R. accomplished of X-Ray diffraction analy-
sis. The manuscript was written and reviewed by G. B., R.
J. and M. M. The ESI was written by A. D.V., J. T. and S. C.-R.

Notes

The authors declare no conflict of interest

ACKNOWLEDGMENT

We are grateful to the CNRS, the Ecole Nationale Supérieure de
Chimie de Rennes and the University of California San Diego.
This work was supported by the “prematuration program” of
CNRS (grant to J.L.), the Agence Nationale de la Recherche
(ANR-19-CE07-0017 ChiCAAC, grant to J.T.), “France Relance”
(for fellowship to A.D.V.) and the U.S. Department of Energy, Of-
fice of Science, Basic Energy Sciences, Catalysis Science Pro-
gram, under Award # DE-SC0009376. The generous gift of ru-
thenium complexes by Umicore AG & Co is gratefully acknowl-
edged. We thank P. Jéhan for HRMS analysis

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(27) Nagyházi, M.; Lukács, Á.; Turczel, G.; Hancsók, J.; Valyon, J.; Bényei, A.; Kéki, S.; Tuba, R. Catalytic Decomposition of Long-Chain Olefins to Propylene via Isomerization-Metathesis Using Latent Bicyclic (Alkyl)(Amino)Carbene-Ruthenium Olefin Metathesis Catalysts. *Angew. Chemie. Int. Ed.* **2022**, *61*, e202204413

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(22) Gawin, R.; Kozakiewicz, A.; Guńka, P. A.; Dąbrowski, P.; Skowerski, K. Bis(Cyclic Alkyl Amino Carbene) Ruthenium Complexes: A Versatile, Highly Efficient Tool for Olefin Metathesis. *Angew. Chem. Int. Ed.* **2017**, *56*, 981–986.

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(26) Eivgi, O.; Guidone, S.; Frenklah, A.; Kozuch, S.; Goldberg, I.; Lemcoff, N. G. Photoactivation of Ruthenium Phosphite Complexes for Olefin Metathesis. *ACS Catal.* **2018**, *8*, 6413–6418.

(27) Nagyházi, M.; Lukács, Á.; Turczel, G.; Hancsók, J.; Valyon, J.; Bényei, A.; Kéki, S.; Tuba, R. Catalytic Decomposition of Long-Chain Olefins to Propylene via Isomerization-Metathesis Using Latent Bicyclic (Alkyl)(Amino)Carbene-Ruthenium Olefin Metathesis Catalysts. *Angew. Chemie. Int. Ed.* **2022**, *61*, e202204413

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(29) Morvan, J.; Vermersch, F.; Zhang, Z.; Falivene, L.; Vives, T.; Dorcet, V.; Roisnel, T.; Crévisy, C.; Cavallo, L.; Vanthuyne, N.; Bertrand, G.; Jazzar, R.; Mauduit, M. Optically Pure C1-Symmetric Cyclic (Alkyl)(Amino)Carbene Ruthenium Complexes for Asymmetric Olefin Metathesis. *J. Am. Chem. Soc.* **2020**, *142*, 19895–19901.

(30) Morvan, J.; Vermersch, F.; Lorkowski, J.; Talcik, J.; Vives, T.; Roisnel, T.; Crévisy, C.; Vanthuyne, N.; Bertrand, G.; Jazzar, R.; Mauduit, M. Cyclic (Alkyl)(Amino)Carbene Ruthenium Complexes for Z-Stereoselective (Asymmetric) Olefin Metathesis. *Catal. Sci. Technol.* **2022**, 381–388.

(31) For the first application of chiral CAAC-TM in asymmetric catalysis, see: Pichon, D.; Soleilhavoup, M.; Morvan, J.; Junor, G. P.; Vives, T.; Crévisy, C.; Lavallo, V.; Campagne, J. M.; Mauduit, M.; Jazzar, R.; Bertrand, G. The Debut of Chiral

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(32) Morvan, J.; Mauduit, M.; Bertrand, G.; Jazzar, R. Cyclic (Alkyl)(Amino)Carbenes (CAACs) in Ruthenium Olefin Metathesis. *ACS Catal.* **2021**, *11*, 1714–1748.

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(50) Some amounts of oligomers (25%) were also formed (See SI for Details).

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(54) Morvan, J.; McBride, T.; Curbet, I.; Colombel-Rouen, S.; Roisnel, T.; Crévisy, C.; Browne, D. L.; Mauduit, M. Continuous Flow Z-Stereoselective Olefin Metathesis: Development and Applications in the Synthesis of Pheromones and Macrocyclic Odorant Molecules. *Angew. Chem. Int. Ed.* **2021**, *60*, 19685–19690.

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(59) Keitz, B. K.; Grubbs, R. H. Ruthenium Olefin Metathesis Catalysts Bearing Carbohydrate-Based N-Heterocyclic Carbenes. *Organometallics* **2010**, *29*, 403–408.

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Ring-Closing - Ring-Closing Enyne - Macrocyclization - Ethenolysis - (Asymmetric) Cross - Ring-Opening-Cross Metathesis

<figure><img src="image_59.png" /></figure>
Ring-Closing - Ring-Closing Enyne - Macrocyclization - Ethenolysis - (Asymmetric) Cross - Ring-Opening-Cross Metathesis

<figure><img src="image_60.png" /></figure>