Visible-light mediated organophotoredox catalytic deuteration of aromatic and aliphatic aldehydes

Patent metadata

Field	Value
Publication number	US-12466775-B2
Application number	US-202017784537-A
Country	US
Kind code	B2
Filing date	Dec 1, 2020
Priority date	Dec 11, 2019
Publication date	Nov 11, 2025
Grant date	Nov 11, 2025

Abstract

Described are methods for preparing a deuterated aldehyde using with a photocatalyst and a hydrogen atom transfer agent in a H 2 O free solvent comprising D 2 O and an organic solvent under an inert gas. The methods may be used to convert a wide variety of aldehydes (e.g., aryl, alkyl, or alkenyl aldehydes) to C-1 deuterated aldehydes under mild reaction conditions.

First claim

What is claimed is:

1 . A method for preparing a deuterated aldehyde of formula:
R Z —C(O)-D
wherein: R Z is alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; wherein the alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl are each optionally substituted with one or more R a , and R Z is optionally deuterated; R a at each occurrence is independently halogen, —CN, —OH, nitro, —O-benzyl, —NH(t-butoxycarbonyl), —NH(benzyloxycarbonyl), or —X—R X , wherein X is bond, O, NH, C(O), OC(O), or C(O)NH; and R X is alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein the R X is optionally substituted, the method comprising: (i) mixing an aldehyde of formula:
R Z′ —C(O)—H

with a photocatalyst and a hydrogen atom transfer agent in a H 2 O free solvent comprising D 2 O and an organic solvent under an inert gas to form a mixture;
wherein the photocatalyst is:

 or a salt thereof;
wherein R Z′ is alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, or heterocyclyl; wherein the alkyl, alkenyl, cycloalkyl, cycloalkenyl, aryl, heteroaryl, and heterocyclyl are each optionally substituted with one or more R b ;
R b at each occurrence is independently halogen, —CN, —OH, nitro, —O-benzyl, —NH(t-butoxycarbonyl), —NH(benzyloxycarbonyl), or —Y—R Y , wherein Y is bond, O, NH, C(O), OC(O), or C(O)NH; and R Y is alkyl, alkenyl, alkynyl, alkoxy, cycloalkyl, aryl, heteroaryl, or heterocyclyl, wherein the R Y is optionally substituted, and

(ii) exposing the mixture of (i) to light, thereby producing the deuterated aldehyde.

2 . The method of claim 1 , wherein R Z is an optionally substituted aryl or an optionally substituted heteroaryl.

3 . The method of claim 1 , wherein R Z is a phenyl, a naphthyl, a pyridinyl, an indolyl, or a benzo[b]thiophene, each of which is optionally substituted.

4 . The method of claim 1 , wherein R Z is an optionally substituted C 2-20 alkyl.

5 . The method of claim 1 , wherein R Z and R Z′ are the same.

6 . The method of claim 1 , wherein the hydrogen atom transfer agent is a R A —SH, R B —C(O)OM, or a combination thereof, wherein
R A is —C 1-4 alkylene-C(O)OC 1-4 akyl or —Si(C 1-4 alkyl) 3 ;
R B is an aryl optionally substituted with 1, 2, 3, or 4 substituents independently selected from the group consisting of halogen, —CN, —OH, nitro, and C 1-4 alkyl; and
M is a counterion other than H + .

7 . The method of claim 6 , wherein the hydrogen atom transfer agent is

PhC(O)ONa, or a combination thereof.

8 . The method of claim 6 , wherein the hydrogen atom transfer agent is a combination of

and PhC(O)ONa.

9 . The method of claim 1 , wherein the inert gas comprises nitrogen (N 2 ).

10 . The method of claim 1 , wherein the deuterated aldehyde is selected from the group consisting of:

11 . The method of claim 1 , wherein the deuterated aldehyde is

12 . The method of claim 1 , wherein the aldehyde of formula
R Z′ —C(O)—H

is selected from the group consisting of:

13 . The method of claim 1 , wherein the level of deuterium incorporation of the —C(O)-D moiety is at least 90%.

14 . The method of claim 13 , wherein in the level of deuterium incorporation of the —C(O)-D moiety is at least 95%.

15 . The method of claim 1 , further comprising isolating the deuterated aldehyde.

Assignees

• Univ Arizona

Inventors

• Wang Wei

Classifications

• C07K5/06078

  and aromatic or cycloaliphatic · CPC title

• C07J9/00

  Normal steroids containing carbon, hydrogen, halogen or oxygen substituted in position 17 beta by a chain of more than two carbon atoms, e.g. cholane, cholestane, coprostane · CPC title

• C07F7/1892

  by reactions not provided for in C07F7/1876 - C07F7/1888 · CPC title

• C07F7/1804

  Compounds having Si-O-C linkages (Si-O-acyl linkages C07F7/1896) · CPC title

• C07D493/04

  Ortho-condensed systems · CPC title