ChemRxiv
These are preliminary reports that have not been peer-reviewed. They should not be regarded as conclusive, guide clinical practice/health-related behavior, or be reported in news media as established information. For more information, please see our FAQs.
1/1
2 files

Siloxy Esters as Traceless Activator of Carboxylic Acids: Boron-Catalyzed Chemoselective Asymmetric Aldol Reaction

preprint
submitted on 27.05.2021, 00:58 and posted on 27.05.2021, 13:21 by Taiki Fujita, Mina Yamane, W. M. C. Sameera, Harunobu Mitsunuma, Motomu Kanai
The catalytic asymmetric aldol reaction of carboxylic acids is among the most useful reactions for the synthesis of biologically active compounds and pharmaceuticals. Despite the existence of many prominent reports, no general method is available to incorporate the aldol motif into complex carboxylic acids and their derivatives at late stages. Chemoselective catalytic asymmetric aldol reaction of multifunctional carboxylic acids is difficult to achieve, due to the high basicity required for enolization and the poisonous chelation of β-hydroxy acid products to Lewis acid catalysts. Herein, we identified that preconversion of carboxylic acids to siloxy esters facilitated the boron-catalyzed direct aldol reaction, leading to the development of carboxylic acid-selective, catalytic asymmetric aldol reaction applicable to multifunctional substrates. The asymmetric boron catalyst stereodivergently controlled the products’ stereochemistry depending on the catalyst’s chirality, not on the stereochemical bias of substrates. Computational studies rationalized the mechanism of the catalytic cycle and the stereoselectivity, and proposed Si/B enediolates as the active species for the asymmetric aldol reaction. The silyl ester formation facilitated both enolization and catalyst turnover through acidifying the α-proton of substrates and attenuating poisonous Lewis bases to the boron catalyst.

Funding

Hybrid Catalysis for Enabling Molecular Synthesis on Demand

Japan Society for the Promotion of Science

Find out more...

Generation of Organometallics from Alkanes by Organoradical-Metal Complex Hybrid Catalysis

Japan Society for the Promotion of Science

Find out more...

Development of sp3 C-H functionalization of simple alkane by dynamic exiton photocatalyst

Japan Society for the Promotion of Science

Find out more...

JP21K15220

Development of carboxylic acid α-position radical activation method for pharmaceutical protecting group free synthesis

Japan Society for the Promotion of Science

Find out more...

ANRI fellowship

Sato Scholarship

History

Email Address of Submitting Author

h-mitsunuma@g.ecc.u-tokyo.ac.jp

Institution

The University of Tokyo

Country

Japan

ORCID For Submitting Author

0000-0001-7609-905X

Declaration of Conflict of Interest

none

Usage metrics

ChemRxiv

Exports