Cobalt‐Catalyzed Carbon‐Carbon Bond Formation: Synthesis and Applications of Enantiopure Pyrrolidine Derivatives^[1]

Abstract

In the presence of cobalt catalysts and tetramethylethylenediamine (TMEDA), the iodine atom in (S)-2-(iodomethyl)pyrrolidines was replaced by an aryl or an alkynyl group from the corresponding Grignard reagent, and the coupling products were obtained in good to excellent yields (16 examples; 75-94% yields). The scope and limitations of this protocol were examined. The stereochemistry of the pyrrolidines was unaffected by the reaction conditions. The coupling products are important building blocks of phenanthroindolizidine alkaloids. Palladium-catalyzed formal [4 + 2] cycloaddition of 2,2'-diiodobiphenyl with the thus-generated (S)-2-(3-trimethylsilyl-2-propynyl)pyrrolidine gave a good yield of the desilylated phenanthrene, which was then converted into unnatural (+)-(S)-tylophorine by the Pictet-Spengler cyclization.

Cobalt, copper, and chromium-catalyzed carbon-carbon coupling reactions using a broad spectrum of Grignard reagents as reaction partners

“…56 21. 57 The catalytic activity of various cobalt complexes such as Co(OAc)2, Co(acac)3, CoCl(PPh3)3, and CoCl2(PPh3)2 was carefully investigated under optimal reaction conditions, the results in terms of catalyst loading and product yield of (S)-20 are summarized in Scheme 6. C-glycosides are prominent carbohydrate analogues with applications as efficacious pharmaceutical compounds.…”

Recent Advances in Cobalt-Catalyzed Csp2 and Csp3 Cross-Couplings

“…chiral iodide 45 with phenylmagnesium chloride in THF in the presence of 5 mol% CoCl 2 (PPh 3 ) 2 and 5 mol% TMEDA furnishes the corresponding pyrrolidine 46 in 84% yield (Scheme 17). 18 Cossy reported a straightforward cross-coupling between various iodo-azetidines, -pyrrolidines and -piperidines and a range of aryl and heteroaryl iodides. 19 Thus, the cross-coupling of iodoazetidine 47 with 3-pyridylmagnesium bromide in the presence of 5 mol% CoCl 2 and 6 mol% ligand 43 provides the coupling product 48 in 91% yield.…”

Cobalt-Catalysed Bond Formation Reactions; Part 2

“…A number of cobalt-catalysed cross-coupling reactions of organomagnesium reagents with aryl halides, [119][120][121][122] vinyl halides 123 or alkyl halides [124][125][126][127][128][129][130][131][132][133] have also been reported. Two selected applications of the cobalt-catalysed cross-coupling reaction are shown in Scheme 47.…”