The Borono–Strecker Reaction: Synthesis of α-Aminoboronates via a Multicomponent Reaction of Carbonyl Compounds, Amines, and B₂pin₂

Abstract

We report the first Borono–Strecker reaction, a multicomponent reaction for the synthesis of α-aminoboronic acid derivatives from readily available carbonyl compounds, amines, and B2pin2. Diverse α-aminoboronates, including aryl-substituted and tertiary examples, were synthesized in moderate to high isolated yields. Compounds were prepared bearing N-(2-pyridyl) groups, which form five-membered rings via N–B coordination, as well as systems bearing noncoordinating N-aryl groups, the latter being isolated and fully characterized for the first time.

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…”

“…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.…”

“…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).…”

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] .…”