Carboxamide-Directed Stereospecific Couplings of Chiral Tertiary Alkyl Halides with Terminal Alkynes

Abstract

Herein, we report the stereospecific Sonogashira coupling of a chiral α-bromocarboxamide possessing a tert-alkyl moiety and an alkyne; this reaction produces a chiral tert-alkylated alkyne in a stereoretentive manner. In this reaction, both the CuBr/bathophen catalyst system and carboxamide directing group are essential for achieving the high enantiospecificities of the couplings. Mechanistic studies of this reaction revealed that the alkynyl copper species is the key intermediate that coordinates to the carboxamide group of chiral α-bromocarboxamide.

Theoretical and experimental mechanistic study of water molecule involvement in the Prilezhaev reaction

“…We have investigated several reaction mechanisms including those for similar reaction systems using the B3PW91 functional and have obtained good results. [28][29][30] Vibrational analyses were performed for the optimized structures to calculate their free energies (DG gas ) under the conditions of 1.0 atm and 298.15 K and to confirm the absence or presence of only one imaginary frequency. IRC calculations 13 were performed to confirm that the optimized TSs connect styrene with styrene oxide, as the reactant and the product.…”

Recent Advances in Transition-Metal-Catalyzed Sonogashira Cross-Coupling Reactions of Alkyl Electrophiles

“…In 2022, Nishikata and co-workers reported the stereospecific Sonogashira coupling of a chiral α-bromocarboxamide possessing a tert -alkyl moiety and a terminal alkyne; this reaction produces a chiral tert -alkylated alkyne in a stereoretentive manner (Scheme 25 ). 32 Both the CuBr/bathophen (4,7-diphenyl-1,10-phenanthroline) catalyst system and carboxamide directing group are essential for achieving the high enantiospecificities of the couplings. Mechanistic studies of this reaction revealed that the Cu-alkynyl species is the key intermediate that coordinates to the carboxamide group of chiral α-bromocarboxamide.…”

Interaction between Divalent Copper Fluoride and Carboxamide Group Enabling Stereoretentive Fluorination of Tertiary Alkyl Halides

“…Our group reported the stereospecific etherifications (via ionic processes) [12] and alkynylations (via Cu I ‐catalyzed radical processes) [13] of α‐bromocarboxamides possessing tert‐ carbon stereocenter. Unfortunately, our reaction methodology proved unsuitable for stereospecific fluorination at tert ‐carbon stereocenter using an inexpensive alkali metal fluoride, [14] which is mechanistically difficult owing to steric hindrance associated with the tert ‐alkyl electrophile and the low nucleophilicity of fluoride.…”