Abstract
Decarboxylative aldol reaction of aliphatic carboxylic acids is a useful method for C–C bond formation because carboxylic acids are an easily available class of compounds. In this study, we found that the decarboxylative aldol reaction of tertiary β-ketocarboxylic acids and trifluoropyruvates proceeded smoothly to yield the corresponding aldol products in high yields and with high diastereoselectivity in the presence of a tertiary amine catalyst. In this reaction, we efficiently constructed a quaternary carbon center and an adjacent trifluoromethylated carbon center. This protocol was also extended to an enantioselective reaction with a chiral amine catalyst, and the desired product was obtained with up to 73% enantioselectivity.
Highlights
Decarboxylative functionalization of aliphatic carboxylic acids is a highly useful method in synthetic organic chemistry [1–9] because the carboxyl group is a fundamental and available functional group
The decarboxylative aldol reaction of β-oxocarboxylic acids has been intensively studied in recent years [2,5,6,10,11] because these acids release carbon dioxide to serve as a formal enolate equivalent [12–20]
To the best of our knowledge, there is only one report on the decarboxylative aldol reaction with tertiary β-oxocarboxylic acids to form an all-carbon quaternary carbon center [24], and there is no report on the enantioselective version, there are some examples of reactions with α,α-difluoro- or α-monofluorocarboxylic acids to form a fluorinated tetrasubstituted carbon center [25–28]
Summary
Decarboxylative functionalization of aliphatic carboxylic acids is a highly useful method in synthetic organic chemistry [1–9] because the carboxyl group is a fundamental and available functional group. A number of decarboxylative aldol reactions with primary and secondary β-oxocarboxylic acids have been reported, including a catalytic enantioselective version [2,5,6,10,11,21–23] Most of these reactions are thought to proceed via the aldol adduct of the β-oxocarboxylic acid and the acceptor, followed by decarboxylative protonation, to yield the desired product (Figure 1a). To the best of our knowledge, there is only one report on the decarboxylative aldol reaction with tertiary β-oxocarboxylic acids to form an all-carbon quaternary carbon center [24], and there is no report on the enantioselective version, there are some examples of reactions with α,α-difluoro- or α-monofluorocarboxylic acids to form a fluorinated tetrasubstituted carbon center [25–28] These reactions proceed via an enol (or enolate) intermediate formed by decarboxylation of the β-oxocarboxylic acid, and the intermediate reacts with the aldol acceptor to give the desired product (Figure 1b).
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
