Enantioselective assembly of tertiary stereocenters via multicomponent chemoselective cross-coupling of geminal chloro(iodo)alkanes

Abstract

Catalytic enantioselective method of consecutive Suzuki–Miyaura alkylations of gem-chloro(iodo)alkanes to form two C–C bonds in one pot transformation is described.

Decarboxylative Halogenation of Organic Compounds

“…Notably, for the first time, the reaction allowed the efficient preparation of various geminal dihaloalkanes ( 345 , 346 , 349 , 350 ) and perfluorinated iodides ( 351 ). 256 − 258 Lactones, N -Boc, N -Cbz, acetyl, and formyl groups remain unaffected during the reaction. Double decarboxylation of remote and 1,1-dicarboxylic acid proceeds smoothly in high yields.…”

“…Refluxing a carboxylic acid with DIH under visible light irradiation furnishes a wide range of primary, secondary, and tertiary bridgehead alkyl iodides in good to excellent yields (Scheme ). Notably, for the first time, the reaction allowed the efficient preparation of various geminal dihaloalkanes ( 345 , 346 , 349 , 350 ) and perfluorinated iodides ( 351 ). − Lactones, N -Boc, N -Cbz, acetyl, and formyl groups remain unaffected during the reaction. Double decarboxylation of remote and 1,1-dicarboxylic acid proceeds smoothly in high yields.…”

A Straightforward Homologation of Carbon Dioxide with Magnesium Carbenoids en Route to α‐Halocarboxylic Acids

“…Upon CaO‐mediated diazotization methyl esters 30 , 31 were smoothly obtained, thus enabling the synthesis of these synthetic valuable motifs in just two sequential, high yielding steps from trivial precursors (Scheme b). Gratifyingly, by applying the elegant Gandelman iododecarboxylation methodology we were able to selectively obtain the chloroiodo derivative 32 in high yield (Scheme c) . Such a three‐different halogen scaffold would represent the formal alkylation product of a MCHICl carbenoid with a benzyl halide.…”

“…Gratifyingly, by applying the elegant Gandelman iododecarboxylation methodology we were able to selectively obtain the chloroiodo derivative 32 in high yield (Scheme 5c). [36] Such a three-different halogen scaffold would represent the formal alkylation product of a MCHICl carbenoid with a benzyl halide. However, according to previous studies by Hoffmann [19b] this highly unstable species (À105 8C) is not particularly suitable for alkylation-type reaction, thus making highly convenient the development of this route.…”

Synthesis of Chiral α-CF3-Substituted Benzhydryls via Cross-Coupling Reaction of Aryltitanates

“…The unexpectedly high reactivity of α-CF 3 -benzyl chlorides led us to explore another approach toward synthesis of compounds of family 1 . We envisioned that starting from 1-chloro-1-bromo-2,2,2-trifluoroethane, or halothanea cheap commercially available anestheticit is possible to perform a sequential one-pot cross-coupling reaction to prepare benzyl chlorides in situ followed by their conversion to 1 . If viable, the use of such a starting material in the catalytic asymmetric cross-coupling protocol would allow for the creation of α-CF 3 -diarylmethanes through a rapid increase of a molecular complexity.…”