Ortho-Deuteration of Aromatic Aldehydes via a Transient Directing Group-Enabled Pd-Catalyzed Hydrogen Isotope Exchange

• DOI: 10.1021/acs.joc.1c01411
• Publication Date: 2021-09-13T14:59:59Z
• Authors: Junhua Kong; Zhi-Jiang Jiang; Jiayuan Xu; Yan Li; Hong Cao; Yanan Ding; Bencan Tang; Jia Chen; Zhanghua Gao
• Keywords: 97 %; Chemical Sciences not elsewhere classified; Biophysics; unexpected reduction; deuterium oxide; Biochemistry; 01 natural sciences; 7. Clean energy; deuterated aromatic aldehydes; Space Science; Environmental Sciences not elsewhere classified; Molecular Biology; Cancer; inexpensive deuterium source; Evolutionary Biology; aromatic aldehydes via; theoretical study indicates; aromatic aldehydes; Computational Biology; transient directing group; control experiments suggest; silver trifluoroacetate resists; 0104 chemical sciences; wide range; deuterium incorporation; Neuroscience

A practical and scalable ortho-selective deuteration of aromatic aldehydes was accomplished by Pd-catalyzed hydrogen isotope exchange with deuterium oxide as an inexpensive deuterium source. The use of tert-leucine as a transient directing group facilitates the exchange, affording a wide range of ortho-deuterated aromatic aldehydes with deuterium incorporation up to 97%. The control experiments suggest that the addition of silver trifluoroacetate resists the unexpected reduction of Pd(II), while the theoretical study indicates a rapid reversible concerted metalation-deprotonation process.