# Synthesis of Functionalized Homoallylic Alcohols via a Salt-Free Three-Component Nickel-Catalyzed Coupling Reaction

Anthony Saint Pol, Maxime Roger, Alexis Mifleur, Pauline Loxq, Laëtitia

Chausset-boissarie, Aurélien Béthegnies, Maël Penhoat, Isabelle Suisse,
Mathieu Sauthier

► To cite this version:

Anthony Saint Pol, Maxime Roger, Alexis Mifleur, Pauline Loxq, Laëtitia Chausset-boissarie, et al. Synthesis of Functionalized Homoallylic Alcohols via a Salt-Free Three-Component Nickel-Catalyzed Coupling Reaction. Advanced Synthesis and Catalysis, 2025, 368, 10.1002/adsc.70183. hal-05520865

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# Synthesis of Functionalized Homoallylic Alcohols via a Salt-Free Three-Component Nickel-Catalyzed Coupling Reaction

Anthony Saint Pol,ª Maxime Roger,ª Alexis Mifleur,ª Pauline Loxq,ª
Laëtitia Chausset-Boissarie,ᵇ Aurélien Béthegnies,ª Maël Penhoat,ᶜ
Isabelle Suisse,ª and Mathieu Sauthierª,\*

Manuscript received: July 9, 2025; Revised manuscript received: October 8, 2025;
Version of record online:

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

Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.70183

<figure><img src="image_3.png" /></figure>

© 2025 The Author(s). Advanced Synthesis & Catalysis published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

**Abstract:** In the presence of a catalytic amount (1 mol%) of Ni(cod)₂ and dppmb (1,2-bis(diphenylphosphino-methyl)benzene)), a three-component coupling reaction between industrially available aldehydes, buta-1,3-diene, and amines leads to the formation of variety of homoallylic alcohols with a highly functionalized 5-aminopent-3-en-1-ol structure. The reaction proceeds with 100% atom economy under mild conditions (80 °C) in isopropanol as solvent. The process accommodates both aliphatic and aromatic aldehydes in combination with cyclic and acyclic secondary dialkyl amines, demonstrating a broad substrates scope. Reaction monitoring shows that the initial rate of the reaction is 39 h⁻¹, and the process reaches a maximum within 3 h of reaction at 80 °C. A competitive reaction has been identified as the hydroamination of 1,3-butadiene that affords light butenyl-amines. The key mechanistic feature of the three-component nickel-catalyzed reaction is the formation of an η³:η¹-allylalkoxy nickel (II) intermediate obtained from the oxidative coupling reaction between a low valent nickel (0) precursor, buta-1,3-diene, and an aldehyde. The amine subsequently reacts as a nucleophile with the electrophilic allyl moiety of this intermediate, while the alkoxy group acts as an internal base facilitating proton transfer that enables the synthesis of 5-aminopent-3-en-1-ol derivatives without any base and salt formation.

**Keywords:** aldehyde, buta-1,3-diene, homogeneous catalysis, nickel, oxidative coupling

## 1. Introduction

Homoallylic alcohols are versatile building blocks, in particular for the synthesis of a variety of oxygen heterocyclic compounds of synthetic[¹⁻⁷] and pharmaceutical importance[⁸⁻¹⁶] such as polyketides natural products. C—C bond formation through nucleophilic allylation of carbonyl compounds is an efficient method for the construction of such scaffolds; however, this protocol

is limited by the use of stoichiometric organometallic reagents.[¹⁷,¹⁸] Carbonyl-ene reactions that involve the reaction between an olefin and an aldehyde is an attractive alternative pathway due to their atom economy.[¹⁹,²⁰] Still, this family of reaction is mainly limited to intramolecular processes unless highly activated alkenes such as enol ethers are used. In the past decade, homoallylic alcohols have been alternatively obtained from the nickel-catalyzed reductive coupling reaction[²¹,²²] of

<footnote>ªCNRS, Centrale Lille, ENSCL, Univ. Artois, UMR 8181—UCCS Unité de Catalyse et Chimie Solide, Univ. Lille,
F-59000 Lille, France</footnote>

<footnote>E-mail: mathieu.sauthier@univ-lille.fr</footnote>

<footnote>ᵇCNRS, INSA Rouen Normandie, Univ Rouen Normandie, Univ Caen Normandie, ENSICAEN, Institut CARMEN UMR 6064,
F-76000 Rouen, France</footnote>

<footnote>ᶜUSR 3290, MSAP (Miniaturisation pour la Synthèse, l'Analyse et la Protéomique), Univ. de Lille, F-59000 Lille, France</footnote>
aldehydes or ketones and conjugated dienes in combina-
tion with a reductant such as Mn,[23] Zn,[24] an organo-
metallic reagent (e.g., BEt₃,[25–29] BMe₃,[30] ZnMe₂,[31–34]
and Et₃SiH[35,36]), or formaldehyde.[37] Recently, nickel
complexes have also been used in combination with pho-
toredox catalysts allowing the synthesis of structurally
diverse homoallylic compounds.[38] Interestingly, in a
mechanistic study, Ogoshi and coworkers[39] demon-
strated that the oxidative cyclization of dienes and car-
bonyl units on Ni(0) species leads to the formation of a
η³:η¹(allyl)(alkoxy)Ni(II) complex I as a key intermedi-
ate (Scheme 1). Alkylmetals having a Lewis acid char-
acter contribute to the cleavage of the nickel–oxygen
bond through the formation of a new O–metal bond.
Interestingly, in the case of ZnMe₂ in place of
ZnEt₂,[40,41] the methylated derivative is obtained thanks
to a reductive elimination step from intermediate I.
Accordingly to this approach, the transformation of this
key intermediate I has been used to synthesize homoal-
lylic alcohols from the use of diboron reagents,[42,43]
aryl boronic acids,[44] and alkenyl- or acyl- zirconium
reagents.[45,46]

In nickel-catalyzed processes involving buta-1,3-
diene, dimerization products are also typically
formed.[47,48] In addition, this transformation generates
a stoichiometric amount of metallic salts as waste.

From an environmental perspective, a key challenge is the development of selective and atom-economical processes.[49] This implies suppressing the use of stoichio-metric amounts of coreagents which are significant sources of salts as by-products. The electrophilic nature of the allylic moiety in η³:η'¹-allylalkoxy nickel intermediate I led us to investigate the use of an amine as organic nucleophile to form a new carbon–nitrogen bond (Scheme 1). This reactivity of the amine opens the way to a three-component reaction (buta-1,3-diene, aldehyde, and amine) that affords homoallylic alcohols with a highly functionalized 5-aminopent-3-enol structure. All the starting reagents are essentially industrially available. The use of buta-1,3-diene offers a significant advantage as it is a simple and symmetric four-carbon feedstock produced on a massive industrial scale, making it an attractive and economical starting material for synthesizing more complex molecules.[50] Furthermore, buta-1,3-diene can also be sourced from renewable feedstocks through to the Lebedev process.[51]

**2. Results and Discussion**

We first explored the reaction with diethylamine as
nucleophile, benzaldehyde 1a, and buta-1,3-diene in

**Previous works : use of a sacrificial co-reagent**

<figure><img src="image_4.png" /></figure>

This work : no sacrificial co-reagent

<figure><img src="image_5.png" /><figcaption>**Scheme 1.** State of the art for the Ni-catalyzed coupling reaction of buta-1,3-diene with carbonyl compounds.</figcaption></figure>
the presence of Ni(cod)₂ as simple Ni(0) precursor stabilized by phosphine ligands. Fortunately, in the presence of 1,4-bis(diphenylphosphino)butane (dppb) as ligand, in toluene, we observed the formation of 5-(diethylamino)-1-phenylpent-3-en-1-ol **3a** in 10% NMR yield after 20 h of reaction (**Table 1**, entry 1). Interestingly, the linear product was obtained as the main reaction product, and less than 2% of the branched isomer was formed. Moreover, no 1:2:1 adduct (two buta-1,3-diene units) was detected.[³¹,³⁴] Encouraged by this result, the reaction conditions were optimized using 0.5 mol% of Ni(cod)₂ with various phosphines. In all reactions presented below, there is no side reaction with the benzaldehyde, and the conversion is matching the yield in **3a**. Some hydroamination by-products resulting from the addition of the amine on buta-1,3-diene were detected.

The use of commercial dppe ((1,2-bis(diphenylphosphino)ethane) or dpppe ((1,5-bis(diphenylphosphino)pentane) instead of dppb ((1,4-bis(diphenylphosphino)butane) afforded the product **3a** in yields lower than 5% (Table 1, entries 2 and 3), whereas the ligand dppmb ((1,2-bis(diphenylphosphinomethyl)benzene) gave the desired product in 56% yield (Table 1, entry 4).

Neither dppf nor the large bite angle Xantphos were effective (Table 1, entries 5 and 6). As we already noticed in the case of the buta-1,3-diene hydroalkoxyla-tion reaction, the presence of a skeleton with 4 carbon atoms between two phosphorous centers appears to be favorable to obtain high yields.[⁵²⁻⁵⁵] Phosphorous sub-stituents are also important and the more basic and sterically hindered diphosphine Hdcpb (1,4-bis(dicyclo-hexylphosphino)butane) that also bears a similar scaffold failed to afford the targeted product **3a** (Table 1, entry 7). Monodentate ligands such as PPh₃ or PCy₃ showed dis-appointing results (Table 1, entries 8 and 9). In order to further optimize the reaction conditions, different solvents were also evaluated. In THF, the product was obtained in 44% yield (Table 1, entry 10), whereas in more polar solvents such as CH₃CN and *i*-PrOH, the yield was increased to 74% and 81% respectively (Table 1, entries 11 and 12). Higher catalyst loading (1 mol% Ni) allowed reaching an improved yield in toluene and *i*-PrOH (Table 1, entries 13 and 14).

The effect of the temperature on this reaction was then studied using dppmb as ligand in *i*-PrOH, and an optimum at 80 °C was observed (Table 1, entries 14–16). Using the optimal conditions with 1 mol% catalyst in

<figure><img src="image_6.png" /><figcaption>**Table 1.** Optimization of the nickel-catalyzed three-component reaction.</figcaption></figure>

<table><thead><tr><th>Entry</th><th>[Ni]<br>[mol%]</th><th>Ligand</th><th>T<br>[°C]</th><th>Solvent</th><th>Yield<sup>a)</sup><br>[%]</th></tr></thead><tbody><tr><td>1</td><td>0.5</td><td>dppb</td><td>80</td><td>Toluene</td><td>10</td></tr><tr><td>2</td><td>0.5</td><td>dppe</td><td>80</td><td>Toluene</td><td>0</td></tr><tr><td>3</td><td>0.5</td><td>dpppe</td><td>80</td><td>Toluene</td><td>4</td></tr><tr><td>4</td><td>0.5</td><td>1,2-dppmb</td><td>80</td><td>Toluene</td><td>56</td></tr><tr><td>5</td><td>0.5</td><td>dppf</td><td>80</td><td>Toluene</td><td>2</td></tr><tr><td>6</td><td>0.5</td><td>Xantphos</td><td>80</td><td>Toluene</td><td>1</td></tr><tr><td>7</td><td>0.5</td><td>Hdcpb</td><td>80</td><td>Toluene</td><td>0</td></tr><tr><td>8<sup>b)</sup></td><td>0.5</td><td>PPh<sub>3</sub></td><td>80</td><td>Toluene</td><td>0</td></tr><tr><td>9<sup>b)</sup></td><td>0.5</td><td>PCy<sub>3</sub></td><td>80</td><td>Toluene</td><td>3</td></tr><tr><td>10</td><td>0.5</td><td>1,2-dppmb</td><td>80</td><td>THF</td><td>44</td></tr><tr><td>11</td><td>0.5</td><td>1,2-dppmb</td><td>80</td><td>MeCN</td><td>74</td></tr><tr><td>12</td><td>0.5</td><td>1,2-dppmb</td><td>80</td><td>*i*-PrOH</td><td>81</td></tr><tr><td>13</td><td>1.0</td><td>1,2-dppmb</td><td>80</td><td>Toluene</td><td>77</td></tr><tr><td>14</td><td>1.0</td><td>1,2-dppmb</td><td>80</td><td>*i*-PrOH</td><td>85</td></tr><tr><td>15</td><td>1.0</td><td>1,2-dppmb</td><td>70</td><td>*i*-PrOH</td><td>72</td></tr><tr><td>16</td><td>1.0</td><td>1,2-dppmb</td><td>90</td><td>*i*-PrOH</td><td>44</td></tr></tbody></table>

**General conditions:** PhCHO **1a** (5.7 mmol), buta-1,3-diene (1 mL, 11.4 mmol, 2.0 eq.), Et₂NH (6.3 mmol, 1.1 eq.), Ni(cod)₂/ligand (1:1.5), solvent (1 mL), *t* = 20 h;

a) Determined by gas chromatography (GC) using dodecane as internal standard;

b) Ni(cod)₂/ligand: 1/3.
i-PrOH at 80 °C, the scope of the Ni(0)/dppmb-catalyzed coupling three-component reaction has been extended to various aldehydes. First, we studied the influence of the substituents on the aromatic groups (Scheme 2A) before extending the reaction to aliphatic aldehydes (Scheme 2B). It is noteworthy that in all cases, compounds 3a-p were obtained as a mixture of stereoisomers (E)-3 and (Z)-3 with an E:Z ratio ranging from 81:19 to 70:30. In most cases, Z and E isomers were separated by silica gel column chromatography. The reaction of benzaldehyde, buta-1,3-diene and diethylamine afforded 3a in 76% isolated yield after purification by silica gel column chromatography (85% yield according to the GC analysis). The use of 1-napthaldehyde gave the corresponding product 3b with 46% isolated yield. Slightly more electron-rich tolualdehyde 1c'' gave the corresponding product 3c in a similar 69% yield with the methyl group is on the para position, whereas on the ortho or meta positions the yield drops to 35% and 40% respectively. p-anisaldehyde gave only 22% yield of 3d. We then studied the effect of an electron-withdrawing group attached on the aromatic ring. Neither p-chlorobenzaldehyde nor p-bromobenzaldehyde led to the desired products 3e' or 3e'', possibly due to the occurrence of an undesired oxidative addition of either C-Cl or C-Br bond to a low valent nickel(0) intermediate. In contrast the fluorine analog, being less prone to oxidative addition reactions, resulted in the formation of 3e with a 65% isolated yield. Higher yields were achieved with carboxymethyl or cyano groups on the para position of the phenyl ring. 3f and 3g were respectively isolated in 68% and 85% yields from methyl 4-formylbenzoate and p-cyanobenzaldehyde. In this latter case, a near quantitative yield was observed by GC (gas chromatography) analysis. These results highlight the significant electronic effect of the phenyl substituents on the reaction yields. Higher isolated yields were generally obtained with electron-withdrawing groups, and up to quantitative yields were obtained with a strong electron-withdrawing group such as a cyano group. The reaction with heteroaromatic aldehydes such as quinoleine derivatives gave more disappointing results with very low yields of the expected reaction products (3h-i). The coordination ability of the quinoleines probably explains the observed low reactivities.

The reaction is not restricted to the transformation of aromatic aldehydes as aliphatic aldehydes have also been efficiently transformed (Scheme 2B). Hydrocinnamaldehyde afforded the desired product 3j with 48% yield, and other aliphatic aldehydes showed comparable reactivities. The product 3k derived from cyclohexanecarboxaldehyde which possesses a cyclic structure was obtained with 42% yield. Branched aldehydes used for the synthesis of 3l-n exhibited reactivities similar to hydrocinnamaldehyde, and 3l-n were obtained with yields that range from 33 to 43%. However, linear

**Scheme 2.** Ni(0)/1,2-dppmb-catalyzed three-component reaction between buta-1,3-diene, aldehydes, and diethylamine. Isolated yield. Under brackets: GC yields calculated using dodecane as internal standard.

aldehydes however showed much lower reactivity, and the products 3o and 3p were for example isolated with 4% yields.

All the tested benzaldehyde derivatives exhibited higher reactivities than aliphatic aldehydes. Competition

<figure><img src="image_7.png" /></figure>

A/ Aromatic aldehydes

<figure><img src="image_8.png" /><figcaption>3a 76% (85%) [E:Z = 75:25]</figcaption></figure>

<figure><img src="image_9.png" /><figcaption>3b 46% (52%) [E:Z = 79:21]</figcaption></figure>

<figure><img src="image_10.png" /><figcaption>3c o-CH₃ = 35% (49%) [E:Z = 82:18]</figcaption></figure>

<figure><img src="image_11.png" /><figcaption>3d 22% (27%) [E:Z = 70:30]</figcaption></figure>

<caption>3c' m-CH₃ = 40% (55%) [E:Z = 82:18]</caption>

<figure><img src="image_12.png" /><figcaption>3e X=F 65% (70%) [E:Z = 82:18]</figcaption></figure>

<figure><img src="image_13.png" /><figcaption>3f 68% [E:Z = 83:17]</figcaption></figure>

<caption>3e' X=Cl 0%</caption>

<figure><img src="image_14.png" /><figcaption>3g 85% (97%) [E:Z = 83:17]</figcaption></figure>

<figure><img src="image_15.png" /><figcaption>3h (<5%)</figcaption></figure>

<figure><img src="image_16.png" /><figcaption>3i (<5%)</figcaption></figure>

B/ Aliphatic aldehydes

<figure><img src="image_17.png" /><figcaption>3j 48% (67%) [E:Z = 75:25]</figcaption></figure>

<figure><img src="image_18.png" /><figcaption>3k 42% (45%) [E:Z = 74:26]</figcaption></figure>

<figure><img src="image_19.png" /><figcaption>3l 31% (33%) [E:Z = 81:19]</figcaption></figure>

<figure><img src="image_20.png" /><figcaption>3m 34% (42%) [E:Z = 78:22]</figcaption></figure>

<figure><img src="image_21.png" /><figcaption>3n 43% (46%) [E:Z = 77:23]</figcaption></figure>

<figure><img src="image_22.png" /><figcaption>3o 4% (6%) [E:Z = 100:0]</figcaption></figure>

<figure><img src="image_23.png" /></figure>
reactions between different aldehydes were conducted with a stoichiometric amount of buta-1,3-diene and diethylamine as limiting reagents in order to better delineate this trend (Scheme 3). When equimolar amounts of benzaldehyde and cyclohexylcarboxaldehyde were introduced in the same reactor, 3a was obtained with 87% of selectivity versus 13% for 3k. Similarly, a reaction between *p*-tolylcarboxaldehyde and *p*-fluorobenzaldehyde showed the formation of the fluorinated derivative 3e with 68% selectivity while 3c'' was obtained with 32% selectivity. Finally, it is noteworthy that in our hands, ketones such as pentan-2-one and acetone did not show any reactivity.

In a second time, different amines have been tested (Scheme 4). This study showed that the reaction can be efficiently conducted using benzaldehyde, buta-1,3-diene, and various dialkylamines. Dimethylamine was added in solution in water. The introduction of water did not impede the catalytic reaction that afforded the expected product 4a with 28% yield. Dibenzylamine was also evaluated as the benzyl groups are removable protecting groups. With this bulkier dialkylamine, 4b was isolated with 73% yield. Cyclic amines have been evaluated as nucleophiles. The product 4c obtained from piperidine was isolated in a good yield of 69%, and morpholine led to the desired product 4d with a similar yield. *N*-methylpiperazine and *N*-phenylpiperazine have been

evaluated, and the corresponding products of reaction 4e and 4f have been isolated with respectively 62% and 54% yields. Cyclic amines with smaller ring sizes also showed interesting reactivities, and 4g was for example isolated with 40% yield from pyrrolidine. Unfortunately, less nucleophilic amines such as *N*-methylaniline or *N*-acetylaniline did not afford the desired product, and the use of primary amines essentially led to the corresponding imines through a condensation reaction with the aldehyde.

In order to better delineate this nickel-catalyzed three-component catalytic transformation, the reaction between benzaldehyde 1a and diethylamine 2a has been monitored over time by using the optimized reaction conditions (Table 1, entry 14). For this purpose, several reactions have been performed in parallel and stopped after defined reaction times. Plotting of benzaldehyde conversion and yields in (Z)-3a and (E)-3a versus time showed that the calculated initial rate of the reaction is 39 h⁻¹, and an optimum is attained after 3 h of reaction (Scheme 5a). The aldehyde conversion is not total and both yields of products and aldehyde conversion reach a plateau. GC and GC-MS analyses give evidence of the formation of *N*,*N*-diethylbutenylamines issuing from the hydroamination reaction of buta-1,3-diene. This reaction is known to be promoted by nickel-based catalysts, and asymmetric versions have been developed with

<figure><img src="image_24.png" /><figcaption>**Scheme 3.** Competition reactions between electron-enriched and electron-depleted aldehydes.</figcaption></figure>
<figure><img src="image_25.png" /><figcaption>**Scheme 4.** Ni(0)/dppmb-catalyzed three-component coupling reaction between buta-1,3-diene, benzaldehyde, and amines. Isolated yield. Under brackets: GC yield calculated using dodecane as internal standard.</figcaption></figure>

substituted dienes.[56,57] Under the catalytic conditions used for this study, three isomers with linear (l) (E/Z mixture) and branched (b) structures are formed as side products of the reaction (Scheme 5b). The E/Z ratio is marginally varying in the course of the reaction and remains close to 3. The branched and linear isomers are formed with the same selectivity at the beginning of the reaction, but it appears clearly that the branched isomer is slowly isomerized in the linear ones until its complete disappearance after 20 h of reaction. This shows that the hydroamination process is reversible.

This isomerization observed with the allylic butenyl-amines formed during the reaction raised the question of the possible reversible formation of the reaction product **3a** which is also an allylic amine derivative. A complementary experiment has been initiated by reacting pure 5-(diethylamino)-1-phenylpent-3-en-1-ol **3a** initially obtained from the reaction between benzaldehyde **1a**, buta-1,3-diene, and diethylamine **2a** with 1 mol% of Ni(cod)$_2$ and 1.5 mol% of dppmb in isopropanol.

After 70 h of reaction at 80 °C, GC analysis evidenced the formation of 26% yield of benzaldehyde

in respect to the initial amount of 5-(diethylamino)-1-phenylpent-3-en-1-ol (Scheme 6). This complementary experiment clearly evidences that, despite the formation of one strong C—C bond and one C—N bond, the reaction is reversible.

Based on previous works[52–55] and on our investigations, we propose the following mechanism for this nickel-catalyzed three components reaction (Scheme 7). One cod ligand of Ni(cod)$_2$ used as precursor is first replaced by the diphosphine, and the second cod ligand is replaced by the aldehyde and buta-1,3-diene. An oxidative coupling reaction then occurs and leads to the formation of a η$^3$:η$^1$-allylalkoxy nickel (II) as key intermediate of the reaction. This type of intermediate has been isolated and characterized in a seminal work from Ogoshi by using $PCy_3$ (tricyclohexylphosphine) as ligand. It is noteworthy that Ogoshi gave clear evidences that this oxidative coupling step is reversible, and the addition of carbon monoxide to a η$^3$:η$^1$-allylalkoxy nickel (II) complex stabilized by one $PCy_3$ ligand in place of the diphosphine led to the formation of free buta-1,3-diene and benzaldehyde along with
<figure><img src="image_26.png" /></figure>

<figure><img src="image_27.png" /></figure>

<figure><img src="image_28.png" /><figcaption>**Scheme 5.** Monitoring over time of the reaction between benzaldehyde **1a**, buta-1,3-diene, and diethylamine **2a**, catalyzed by Ni(0)/dppmb in *i*-PrOH. a) Products of the 3 component-coupling reaction. b) Side products issuing from the hydroamination reaction. General conditions: PhCHO **1a** (5.7 mmol), buta-1,3-diene (1 mL, 11.4 mmol), Et₂NH **2a** (6.3 mmol), Ni(cod)₂/dppmb (1:1.5), *i*-PrOH (1 mL). Determined by GC analysis with dodecane as internal standard.</figcaption></figure>

Ni(CO)₃(PCy₃) as the main product.[³⁹] It is likely that this intermediate with the phosphine acting as a monodentate ligand is formed albeit in a low amount in the reaction medium. Catalytic results show that this low quantity is enough to yield the final product of reaction even with 1 mol% of catalyst loading. Catalytic tests did

not show any formation of product with monophosphines such as PCy₃. The use of dppmb and dppb is indeed crucial to prevent the buta-1,3-diene dimerization.[⁵⁵] Tightly chelating diphosphines clearly impede the reaction, and we assume that the dppe and dppp ligands don't afford any catalytic reactions by preventing
<figure><img src="image_29.png" /><figcaption>**Scheme 6.** Reversibility of the reaction: catalytic transformation of 5-(diethylamino)-1-phenylpent-3-en-1-ol **3a** in benzaldehyde **1a**, buta-1,3-diene, and diethylamine **2a**.</figcaption></figure>

<figure><img src="image_30.png" /><figcaption>**Scheme 7.** Proposed catalytic cycle for the three-component reaction between buta-1,3-diene, aldehydes, and amines.</figcaption></figure>

the coordination of both aldehyde and buta-1,3-diene and, hence, the oxidative coupling step. The nickel diphosphine catalyst however does not completely prevent the hydroamination of buta-1,3-diene that occurs concomitantly to this multicomponent transformation. Still, this side reaction remains limited. The second key step of the multicomponent reaction is the nucleophilic attack of the dialkyl amine on one of the electrophilic allylic carbons of the η³:η¹-allylalkoxy nickel (II) intermediate. The linear product is obtained as a major

isomer from the attack of the nucleophile on the less sterically hindered terminal carbon of the allylic moiety. The experiments depicted in Scheme 6 clearly show that the reaction is reversible; the product of reaction can be converted back to the starting materials by the Ni(cod)₂/dppmb catalytic system. Allylic amines are able to react with low valent Ni(0) species, and they have been for example used as allylation reagents in allylic alkylation reactions.[58,59] The allylic product of reaction with the 5-aminopent-3-en-1-ol scaffold can thus be involved
in an oxidative addition step with a low valent Ni(0) species followed by a deprotonation of the alcohol by the amide. This reaction regenerates the η³:η'¹-allylalkoxy nickel (II) intermediate, thus opening the way to a reversibility of the reaction.

### 3. Conclusion

The nickel-catalyzed reaction involving an oxidative coupling of buta-1,3-diene and an aldehyde followed by a nucleophilic attack of an amine efficiently affords aminoalcohols with the 5-aminopent-3-en-1-ol scaffold. The molecules thus obtained are highly functionalized and open the way to more elaborated structures by taking advantage of the amine, alcohol, and alkene groups. The reaction is advantageously conducted with a low amount (1 mol%) of nickel as an abundant metal. The catalyst is simply generated in situ from Ni(cod)₂ and dppmb. This atom-economical catalytic reaction is in competition with the hydroamination of buta-1,3-diene. Still, this latter reaction remains limited and the three-component reaction has been used for the conversion of benzaldehyde derivatives or aliphatic aldehydes combined with cyclic and acyclic aliphatic secondary amines. The study of the reaction scope shows that highest yields are obtained with electron poor aldehydes. On a mechanistic point of view, it is noteworthy that the reaction is reversible and the product of reaction can be converted back to the starting materials. This reaction opens a clean way to the synthesis of pent-3-en-1-ol scaffolds from readily accessible starting materials that are industrially available. The fundamental principle of using a nucleophilic attack on the allylic moiety of the nickel intermediate I clearly opens the way to several new catalytic transformations. Other nucleophiles than amines can be very likely used and the corresponding studies will be reported in due time.

### Acknowledgements

We acknowledge the Ministère de l'Enseignement Supérieur, de la Recherche et de l'Innovation, the CNRS, the Université de Lille, and the Hauts-de-France Region (A. S. P.'s fellowship) for their financial support. We acknowledge C. Delabre for GC and GC-MS analysis.

### Conflict of Interest

The authors declare no conflict of interest.

### Data Availability Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

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