Cobalt-Catalyzed Diastereo- and Enantioselective Allyl Addition to Aldehydes and α-Ketoesters through Allylic C–H Functionalization

Abstract

Catalytic reactions that can generate nucleophilic allyl–metal intermediates directly from simple alkenes without prefunctionalization, and ones that produce various homoallylic alcohols diastereo- and enantioselectively are of great importance in organic synthesis. Transformations that accomplish these two tasks simultaneously are in high demand, particularly if the catalysts, substrates and reagents are inexpensive and easy to access. Here we report a catalytic process that chemoselective formation of nucleophilic allyl–cobalt complexes through oxidative allylic C–H cleavage of alkenes followed by site-, diastereo- and enantioselective addition to aldehydes and α-ketoesters. The enantioenriched products that are otherwise difficult to access are obtained in up to 96% yield, with >95:5 dr and 98:2 er. The cobalt-based catalyst is derived from a commercially available chiral phosphine ligand. The utility of the method is demonstrated through enantioselective formal synthesis of lithospermic acid and total synthesis of dihydrodehydrodiconiferylalcohol.

Dual-functional cobalt catalyst enables electrocatalytic allylic C–H alkylation

“…2, top). Monosubstituted alkenes bearing diverse substituents were tolerated, including i) electrophilic groups such as epoxide (5) and alkyl chloride (6), bromide (7) and sulfonates (8, 9), ii) acid/base sensitive Boc-protected amino esters (16,17) and β,-unsaturated amides (18,21), as well as iii) oxidation-labile functionalities such as aldehyde (19), amine (20), anilide (21), and sulfonamide (22). The presence of a sterically bulky trimethylsilyl group at the -position resulted in a reduced yield of 35% (23) but did not affect the preference for the cleavage of the -C-H bond.…”

“…Cobalt represents an attractive alternative to noble metals for transition-metal catalysis due to its greater natural abundance and cost efficiency. [11][12][13][14][15][16][17][18] In view of the challenges associated with the selective functionalization allylic C-H bonds of unactivated alkenes through organometallic activation, we envision a radical-based electrocatalytic approach [19][20][21][22][23][24][25][26][27][28][29] to expand the scope of allylic C-H alkylation and eliminate the need for external chemical oxidants (Fig. 1b).…”

Dual-functional cobalt catalyst enables electrocatalytic allylic C–H alkylation

“…2, top). Monosubstituted alkenes bearing diverse substituents were tolerated, including i) electrophilic groups such as epoxide (5) and alkyl chloride (6), bromide (7) and sulfonates (8, 9), ii) acid/base sensitive Boc-protected amino esters (16,17) and β,-unsaturated amides (18,21), as well as iii) oxidation-labile functionalities such as aldehyde (19), amine (20), anilide (21), and sulfonamide (22). The presence of a sterically bulky trimethylsilyl group at the -position resulted in a reduced yield of 35% (23) but did not affect the preference for the cleavage of the -C-H bond.…”

“…Cobalt represents an attractive alternative to noble metals for transition-metal catalysis due to its greater natural abundance and cost efficiency. [11][12][13][14][15][16][17][18][19] In view of the challenges associated with the selective functionalization allylic C-H bonds of unactivated alkenes through organometallic activation, we envision a radical-based electrocatalytic approach [20][21][22][23][24][25][26][27][28][29][30] to expand the scope of allylic C-H alkylation and eliminate the need for external chemical oxidants (Fig. 1b).…”

Asymmetric Addition of Allylsilanes to Aldehydes – A Cr/Photoredox Dual Catalytic Approach Complementing the Hosomi–Sakurai Reaction

“…7 Important contributions include for example the utilization of allylic acetates, 8,9 allylic halides, 10,11 allenes [12][13][14] or allylic C-H functionalization. 15 Among this variety of reagents, allylsilanes turned out to be an ideal allyl source, 16 standing out due to their abundance and low toxicity. In addition, they show a remarkably high stability, which simplifies their synthesis, purification and storage and results in a huge library of functionalized allylsilane derivatives being easily accessible.…”