Chemoselective Reduction of Tertiary Amides under Thermal Control: Formation of either Aldehydes or Amines

Abstract

The chemoselective reduction of amides in the presence of other more reactive reducible functional groups is a highly challenging transformation, and successful examples thereof are most valuable in synthetic organic chemistry. Only a limited number of systems have demonstrated the chemoselective reduction of amides over ketones. Until now, the aldehyde functionality has not been shown to be compatible in any catalytic reduction protocol. Described herein is a [Mo(CO)6 ]-catalyzed protocol with an unprecedented chemoselectivity and allows for the reduction of amides in the presence of aldehydes and imines. Furthermore, the system proved to be tunable by variation of the temperature, which enabled for either C-O or C-N bond cleavage that ultimately led to the isolation of both amines and aldehydes, respectively, in high chemical yields.

Borinic Acid Catalysed Reduction of Tertiary Amides with Hydrosilanes: A Mild and Chemoselective Synthesis of Amines

“…Very recently, Adolfsson et al. reported an impressive reduction of amides with [Mo(CO) 6 ] and TMDS that readily tolerated aldehydes and ketones . Zhang and co‐workers pioneered in 2009 by using the boron‐based non‐metal catalyst B(C 6 F 5 ) 3 1 in combination with Ph 2 SiH 2 (Scheme ) …”

“…Very recently,A dolfsson et al reported an impressive reduction of amides with [Mo(CO) 6 ]a nd TMDS that readily tolerated aldehydes and ketones. [5] Zhang and co-workersp ioneered in 2009 by using the boron-based non-metal catalystB (C 6 F 5 ) 3 1 in combinationw ith Ph 2 SiH 2 (Scheme 1). [6] The electron depleted borane 1 wasu sed to reduce various functional groups, such as amides, indoles, ketones,e nol ethers,o re namines.…”

Mild Reductive Functionalization of Amides into N‐Sulfonylformamidines

“…We have previously reported on a highly chemoselective protocol for amide reduction into either amines or aldehydes . The Mo(CO) 6 ‐catalyzed system was further investigated and it was discovered that enamines could also be accessed .…”

“…We have previously reported on ah ighly chemoselective protocolf or amide reduction into either amines or aldehydes. [19] The Mo(CO) 6 -catalyzed system was further investigated and it was discovered that enamines could also be accessed. [20] Recently,w ed emonstrated the reductivef unctionalization of amides into 4,5-dihydroisoxazoles and triazolines.…”

Chemoselective Reduction and Alkylation of Carbonyl Functions Using Phosphonium Salts as an <i>in Situ</i> Protecting Groups

“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Additionally, there are several reports for reversing the reactivities of carbonyl functions in chemoselective catalytic reduction by using transition metals. 21,22) However, most of the reported methods have drawbacks, such as narrow substrate scopes, the need for strict stoichiometric control, and the use of expensive reagents; therefore, although they simplify the preparative sequences, these methods have rarely been used in synthetic organic chemistry. More practical and simple methods for the selective transformation of carbonyl groups are therefore required.…”