title: Cobalt(I)-catalyzed regioselective allylic alkylation reactions of tertiary allyl carbonates
title: Kobalt(I)-katalysierte regioselektive Allylalkylierungsreaktionen von tertiären Allylcarbonaten
titleType: AlternativeTitle
Creators: name: Andreetta, Philip (Dr.)
Publisher: name: Philipps-Universität Marburg
Year: 2024
Subjects: Chemistry &amp; allied sciences
Chemie
coordination cobalt(I) complexes
theoretical calculations
Allylalkylierung
Kobalt(I)-katalysierte Allylalkylierungsreaktion unter Verwendung gut definierter Co(I)-Komplexe
Kobaltkatalyse
Cobalt catalysis
allylic alkylation
koordinierte Kobaltkomplexe

description: Catalysis plays a central role in developing environmentally friendly and efficient chemical processes for the synthesis of chemicals from abundant and renewable feedstocks. On the other hand, many relevant industrial catalytic processes, such as hydrogenation, olefin metathesis and cross-coupling reactions, uses noble transition metals (Pd, Rh, Ir, Ph), which are low abundand, relatively toxic and associated with high costs. To address these sustainability concerns, there has been a resurgence in the use of first-row transition metals, commonly referred to as base metal catalysts (Mn, Fe, Co, Ni), as greener alternatives.
Among these metals, cobalt has been widely used in organic synthesis. Currently, cobalt-catalyzed methods for carbon-carbon bond formation are gaining attention as environmentally benign alternatives to methods involving its heavier congeners, Rh and Ir. Low valent cobalt(I) species are often proposed as the active catalytic species, which are formed in situ either through reduction through metal reductants (Zn or Mn) or using photoredox catalysts in reductive quenching cycles. However, for many cobalt-catalyzed reactions, the complete mechanistic scenario remains unclear, with reaction development often relying on empirical screening of catalysts and reaction conditions rather than a more rational design. In this context, previously reported cobalt-catalyzed allylic alkylation methods, which used allyl carbonates as electrophiles under reductive conditions, efficiently afforded branched alkylated products with high regioselectivity. However, the mechanistic understanding of these reactions was very narrow. Thus, the objective of this thesis was to develop allylic alkylation reactions by using well-defined cobalt(I) complexes, and shed light into the mechanism. Thus, a family of well-defined cobalt(I) chloride catalysts bearing commercially available (bis)phosphino ligands was synthesized and tested for their catalytic performance in allylic alkylation reactions. In addition, the isolation of well-defined cobalt(I) complexes facilitates the identification of the active catalytic species, thus facilitating the mechanistic investigations. Thus, a combination of mechanistic experiments and theoretical studies was performed to further elucidate the underlying catalytic cycle. 
During this work, the synthesis and characterization of a family of well-defined Co(I) complexes bearing commercially available (bis)phosphine ligands was performed. Complexes (P,P)CoCl(PPh3) were prepared in high yields by direct coordination of the (bis)phosphine ligands to the cobalt(I) precursor (PPh3)3CoCl. Moreover, (P,P)CoCl(PPh3) are excellent precursors to synthesize in high yields the corresponding cationic Co(I) arene complexes, [(P,P)Co(η6-C7H8)][BArF4], by reaction with Na[BArF4] in aromatic solvent. The development of a straightforward synthesis for well-defined cobalt(I) complexes has facilitated the investigation of their catalytic activity in allylic alkylation reactions. 
Thus, the allylic alkylation of tertiary allyl carbonates using 1,3-diesters and 1,3-ketoesters as nucleophiles catalyzed by cobalt(I) complexes under mild conditions was explored. The addition of NaBF4 as additive was crucial for observing moderate to good yields of the alkylated product. The additive might have a dual role, it could facilitate the formation of the cationic cobalt(I) complex by abstracting the chloride or, the sodium cation, could also coordinate to the carbonyl group of the carbonate and increase the electrophilicity of the carbonyl group. Second, in all cases, the branched regioisomer was observed as the major product, which indicates that the reaction is high regioselective. Third, the bite angle of the Co(I) catalytic has an impact on the catalytic activity: Co(I) complexes with a smaller bite angles exhibited higher catalytic activity compare to the one with a larger bite angles. The best catalysts showed to be (dppp)Co(PPh3). The developed base-free methodology showed a broad functional group tolerance, although some limitations were encountered, allyl carbonates bearing azide, aldehyde and pyridine groups are not active in the transformation. In addition, the presence of an ester group at the nucleophile is a prerequisite for achieving the alkylation reaction. Notably, the developed method allows for the allylic alkylation of tertiary allyl carbonates in the presence of secondary ones. This unusual selectivity is complementary not only to the Tsuji-Trost reaction, but also to the dual cobalt/organophotoredox visible light allylic alkylation method reported previously. This difference in selectivity between thermal and photochemical conditions suggests a different catalytic cycle. 
Mechanistic investigations in combination with theoretical calculations using DFT methods support a Co(I)/Co(III) catalytic cycle for the developed cobalt(I)-catalyzed allylic alkylation reaction. The reductive elimination step at the -allylcobalt(III) is the regioselective determining step, indeed the calculated energy for the transition state that leads to the branched product is lower in energy than the transition state leading to the linear product. NBO analysis Natural Bond Orbital (NBO) analysis suggests that differences on the non-covalent interactions at the two transition states are crucial for the regioselective reductive elimination step, being more favorable for the transition state towards the branched product.
This work contributed in the field of Co(I)-catalyzed allylic alkylation reactions, shedding light on the mechanism, on the selectivity and on the development of novel Co(I)-catalyzed allylic alkylation reactions. Future perspectives could be the synthesis and characterizations of a family of well-defined Co (0) complexes for the regioselective allylic alkylations of secondary allyl carbonates.