Formation of C(sp³)–C(sp³) Bonds through Nickel‐Catalyzed Decarboxylative Olefin Hydroalkylation Reactions

Abstract

Olefins and carboxylic acids are among the most important feedstock compounds. They are commonly found in natural products and drug molecules. We report a new reaction of nickel-catalyzed decarboxylative olefin hydroalkylation, which provides a novel practical strategy for the construction of C(sp(3) )-C(sp(3) ) bonds. This reaction can tolerate a variety of synthetically relevant functional groups and shows good chemo- and regioselectivity. It enables cross-coupling of complex organic molecules containing olefin groups and carboxylic acid groups in a convergent fashion.

Radicals: Reactive Intermediates with Translational Potential

“… 170 Inspired by our work, others have adapted RAEs for additional Ni-catalyzed transformations. 171 Judging by the hundreds of different known reactions of alkyl halides in SET-based cross-couplings, it is anticipated that RAEs will find wide use and permit a broad array of carboxylic acid building blocks to be enlisted in similar transformations.…”

Nickel-Catalyzed Enantioselective Cross-Coupling of N-Hydroxyphthalimide Esters with Vinyl Bromides

“…10 These electrophiles are prepared from the corresponding carboxylic acids, and have been recently demonstrated as C(sp 3 ) substrates for Ni-catalyzed Negishi, 11a,b Suzuki, 11c and reductive 12 cross-coupling reactions to generate racemic products (Scheme 1). 13,14 However, NHP esters have not been demonstrated as competent coupling partners in Ni-catalyzed enantioselective cross-coupling reactions. We recognized that the use of NHP esters might be advantageous for substrates in which the corresponding alkyl chlorides are unstable or challenging to prepare.…”

Alkyl Halides as Both Hydride and Alkyl Sources in Catalytic Regioselective Reductive Olefin Hydroalkylation

“…of Mn being optimal (Table 1 entries 57). Switching Mn to Zn as the reluctant led to a drastic reduction in yield and regioselectivity ( Performing the hydroalkylation by replacing Mn with hydrosilane/base as the hydride source [39][40][41][42][43] led to lower yields of 6a (see Supporting Information for details), highlighting the importance of the reductive conditions. It merits mention that 1.5 equiv.…”

“…but with additional additives, or involve excess alkene partner. [39][40][41][42][43]45 Substrate scope. With the established conditions in hand, we proceeded to evaluate the scope by examining various functionalized aliphatic halides and alkenyl amides (Fig.3).…”

“…It merits mention that previous methods which rely on hydrosilane/base to generate the hydride source may cause undesired silylation side reactions with hydroxyl groups. 45 Both acid-labile (acetal 6o) and base-labile (6k, 6r and boronate 6t) functionalities, which could be vulnerable under conditions that require acid/base additives [39][40][41][42][43][44][45] The protocol is compatible with both primary and secondary alkyl halides bearing Brønsted/Lewis acidic and basic functionalities, including those derived from complex bioactive molecules. Both mono-and 1,2-disubstituted alkenyl amides are tolerated in the catalytic system.…”