Copper‐Catalyzed One‐Pot Denitrogenative–Dehydrogenative–Decarboxylative Coupling of β‐Ketoacids with Trifluorodiazoethane: Facile Access to Trifluoromethylated Aldol Products

Abstract

A novel copper-catalyzed one-pot cross-coupling of β-ketoacids with in situ generated trifluorodiazoethane has been developed. This reaction provides a direct and efficient method, in which one C-C bond and one C-O bond were formed in a carbenoid center with concomitant denitrogenation-dehydrogenation-decarboxylation, to afford trifluoromethylated aldol products. In several preliminary experiments, good to high enantioselectivities were also obtained.

Stereoarrayed CF3‐Substituted 1,3‐Diols by Dynamic Kinetic Resolution: Ruthenium(II)‐Catalyzed Asymmetric Transfer Hydrogenation

“…Recrystallization from hexane/EtOAc led to the stereopure diol. Noteworthy, ( R )‐ 2 a was prepared in 93 % ee by a copper(I)‐catalyzed asymmetric cross‐coupling of 3‐oxo‐3‐phenylpropionic acid with the hazardous CF 3 CHN 2 , while an enzymatic resolution‐based multistep synthesis provided ( R )‐ 2 a and anti ‐ 3 a in 92 % ee and 96 % de ( S , S ), respectively . Nevertheless, to the best of our knowledge no metal‐catalyzed asymmetric reduction has been described so far for such diketones.…”

Emergence of Copper‐Mediated Formation of C–C Bonds

“…A one‐pot transformation involving denitrogenative, dehydrogenative, and decarboxylative coupling of β‐keto acids and trifluorodiazoethane was reported by Ma et al (Scheme ) . This coupling is a rare example of C(sp 3 )–C(sp 3 ) bond formation with introduction of the trifluoromethyl motif.…”

β‐Trifluoromethyl α,β‐unsaturated Ketones: Efficient Building Blocks for Diverse Trifluoromethylated Molecules

“…Ma and coworkers in 2014 have developed a one-pot synthetic protocol involving denitrogenative-dehydrogenativedecarboxylative coupling of β-ketoacids 16 and trifluorodiazoethane for efficient preparation of a variety of trifluoromethylated aldol adducts 15, which can be further converted to the trans-β-trifluoromethyl enones 3 in high yields (Scheme 4). [22] Further, Boreux, Riant and Gagosz together in 2018 developed another strategy for the synthesis of βtrifluoromethyl α,β-unsaturated ketones 3 by the goldcatalysed [3,3]-sigmatropic rearrangement of propargylic carboxylates 18 (Scheme 5). The cheaper and stable ethyl trifluoroacetate was used as CF 3 source for the required CF 3 -subtituted propargylic carboxylate substrates.…”