Ru‐Catalyzed Selective C(sp³)−H Monoborylation of Amides and Esters

Abstract

A ruthenium‐catalyzed method has been developed for the C(sp3)−H monoborylation of various unactivated alkyl and aryl amides and challenging esters, with a low‐cost and bench‐stable boron source, providing boronates with exclusive selectivity, high efficiency, and high turnover number (up to 8900). This novel strategy may offer a versatile and environmentally friendly alternative to current methods for selective C(sp3)−H borylation that employ even more expensive metals, such as iridium and rhodium.

Primary trifluoroborate-iminiums enable facile access to chiral α-aminoboronic acids via Ru-catalyzed asymmetric hydrogenation and simple hydrolysis of the trifluoroborate moiety

“…The study of ruthenium catalysts revealed that Ru-(p-cymene)-phosphine ligand complexes showed very low activity and no enantioselectivity in the hydrogenation of substrate 2a (Table S3, entries 2-14). The RuOAc 2 -phosphine complexes showed limited enantioselecivity and also low conversions (Table S3, entries 15, 16), while the RuCl-diphosphine-diamine complexes performed slightly better in terms of enantioselecivity, but with similarly meagre conversions (Table S3, entries [17][18][19][20][21][22][23][24]. The dimethylamine adducts of RuCl-phosphine complexes were slightly more active but gave low enantioselectivity (Table S3, entries [25][26][27].…”

“…Many of the existing methods are either racemic, allow limited scope of substrates, or do not enable the synthesis of N -unprotected derivatives. 11,18–33,35…”

“…11,18 In recent years, this eld has continued to ourish with many exciting methods being developed. [19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Among recent methodologies, discoveries of Yudin 32 and Bode 33 caught our attention. Namely, in these reports triuoroborate-iminiums (TIMs) and MIDA-protected iminoboronates were prepared from acylboranes, 34 and converted to racemic N-substituted a-aminoboronic acid derivatives with borohydride reagents (Scheme 1).…”

“…Many of the existing methods are either racemic, allow limited scope of substrates, or do not enable the synthesis of N-unprotected derivatives. 11,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]35 Based on our recent research, 35 we envisioned that unsubstituted primary TIMs (pTIMs) could provide access to chiral aaminoboronic acids using asymmetric hydrogenation. Moreover, the use of pTIMs would eliminate the N-deprotection step to obtain the free amino group, thereby shortening the overall synthetic sequence.…”

Catalytic Approach to Diverse α‐Aminoboronic Acid Derivatives by Iridium‐Catalyzed Hydrogenation of Trifluoroborate‐Iminiums

“…Recently, the challenge of α‐aminoboronic acid synthesis was tackled by reductive amination of acylboranes (Scheme 1, entries 1 and 2), [10,11] borylation of amides, [12–14] hydroboration of enamides, [15] electrophilic amination of gem ‐diborylalkanes (Scheme 1, entry 3), [16] a cascade copper‐catalyzed aminoboration of alkynes, [17] and also an interesting one‐pot borono‐Strecker reaction [18] . Two complementary rhodium‐catalyzed approaches were disclosed independently by two research groups, successfully hydrogenating α‐boryl enamides (Scheme 1, entry 4) [19,20] .…”