Science 369 (6503), 557-561.

DOI: 10.1126/science.abb4129originally published online June 18, 2020

Direct reversible decarboxylation from stable organic acids in dimethylformamide solution

Duanyang Kong, Patrick J. Moon, Erica K. J. Lui, Odey Bsharat and Rylan J. Lundgren

Abstract

Many classical and emerging methodologies in organic chemistry rely on carbon dioxide (CO2) extrusion to generate reactive intermediates for bond-forming events. Synthetic reactions that involve the microscopic reverse—the carboxylation of reactive intermediates—have conventionally been undertaken using very different conditions. We report that chemically stable C(sp3) carboxylates, such as arylacetic acids and malonate half-esters, undergo uncatalyzed reversible decarboxylation in dimethylformamide solution. Decarboxylation-carboxylation occurs with substrates resistant to protodecarboxylation by Brønsted acids under otherwise identical conditions. Isotopically labeled carboxylic acids can be prepared in high chemical and isotopic yield by simply supplying an atmosphere of 13CO2 to carboxylate salts in polar aprotic solvents. An understanding of carboxylate reactivity in solution enables conditions for the trapping of aldehydes, ketones, and α,β-unsaturated esters.

Simple swaps of CO2

The loss of carbon dioxide (CO2) from carboxylic acids is a common reaction in both biochemical and synthetic contexts, but it has generally involved catalysis or prolonged heating. Kong et al. now report that certain polar solvents, such as dimethylformamide, promote reversible CO2 loss all by themselves from carboxylates bridged by one carbon to aromatic rings. With electron-withdrawing substituents on the ring, isotopically labeled CO2can be efficiently swapped in even at room temperature. Alternatively, reaction with aldehydes leads to alcohol formation.

Conclusion：

Efficient reversible decarboxylation-carboxylation masks the inherent reactivity of otherwise stable carboxylates. An appreciation of this phenomenon enables simple, direct protocols for isotopic exchange of carboxylic acids with 13CO2 andmethods for decarboxylative carboncarbon bond forming reactions. The potential for reversible decarboxylation should be considered more generally when designing and executing decarboxylative functionalization processes.

Note：方法挺好，标记的二氧化碳源成本较高。有一个不成熟的想法，如果能发明一种非辐射（非反应堆）的方案制备13C或者14C源多好啊！