Reframing primary alkyl amines as aliphatic building blocks

Abstract

This review covers recent and historical aliphatic deaminative functionalization reactions to encourage the use of primary amines as aliphatic building blocks.

Development of copper-catalyzed deaminative esterification using high-throughput experimentation

“…Recently C-N bond activation has emerged as an important synthetic strategy to exploit the commercial and natural prevalence of the amine functional group [18][19][20][21] , leading us to consider the transformation of a C-N bond into a C-O bond. A handful of C-N to C-O transformations have been reported [22][23][24][25][26][27][28][29][30] , but this transformation class remains largely unexplored.…”

Direct Deamination of Primary Amines via Isodiazene Intermediates

“…Unfortunately, a direct, functionally tolerant, aliphatic deamination protocol remains elusive (Figure B). Although aliphatic primary amines are ubiquitous in pharmaceuticals and natural products, their poor nucleofugality renders substitution chemistry highly challenging. − Accordingly, the state-of-the-art for aliphatic deaminative substitution involves prefunctionalization of primary amines to Katritzky-type pyridinium salts, which undergo photocatalytic or metal-catalyzed cross-coupling reactions. − Such pyridinium salts can be reduced to alkanes with NaBH 4 upon pyrolysis, though the resulting two-step procedure is unsurprisingly hostile to complex molecules. , Sporadic reports for milder deaminations of Katritzky salts have been disclosed, often as side reactions among other transformations, but no systematic study has been conducted. , Regardless, prefunctionalization of the amine in a separate step is required in pyridinium-based routes as well as in other reported approaches (e.g., via bis­(sulfonyl)­amides). − The remaining literature for direct deamination uniformly requires harsh reagents or conditions, and/or suffers from low functional group tolerance and yield. − One recent advance from the Oestreich group generates carbocationic intermediates with superstoichiometric phenylsilane . Despite enabling benzylic α-secondary and α-tertiary deamination, this method requires high temperatures and suffers from carbocation rearrangement.…”

Three-component reaction access to S-alkyl dithiocarbamates under visible-light irradiation conditions in water

“…Aliphatic primary amines are common and important building blocks, and they are abundant and natural feedstocks which can also be easily prepared from readily available chemical raw materials. 7 The construction of C–C and C-heteroatom bonds via amino group activation and functionalization from aliphatic primary amines is of great significance in realizing molecular diversity synthesis. Recently, deamination of Katritzky salts which can be easily prepared in one step from aliphatic primary amines has proven to be a novel and convenient approach to the generation of alkyl radicals.…”