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

Abstract

A series of structurally diverse benzyl protected trifluoroborate‐ammoniums were prepared in good to high yields by an efficient hydrogenation of corresponding trifluoroborate‐iminiums using Crabtree's catalyst. Subsequent N‐ and B‐deprotections were demonstrated on selected examples to provide several α‐aminoboronic acids. Preliminary experiments on asymmetric version of the reaction indicated a correlation between E/Z‐ratio in the trifluoroborate‐iminium substrate and enantioselectivity. The broad scope, operational simplicity and efficiency of the presented method imply its high potential for a facile access to libraries of α‐aminoboronic acid derivatives that can be used in medicinal chemistry applications and beyond.

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

“…in MeCN and DMF even at 60 °C in the presence of molecular sieves (3 Å) (Table S1, entries 1–3†), although these solvents enabled the preparation of secondary and tertiary TIMs. 33,35 More encouraging results with 38% yield of 2a in 20 h (0.2 M concentration) were observed in MeOH at room temperature (Table S1, entry 4†). Interestingly, the reaction conducted at 0.05 M concentration afforded 62% conversion due to increased solubility of NH 4 Cl (Table S1, entry 5†).…”

“…50,51 As we have shown recently, only Bode's SiCl 4 method 33 enabled the conversion of pTAMs to the aminoboronic acids while other methods failed. 35 However, huge excess (10 eq.) of difficult-to-handle SiCl 4 was needed to transform pTAMs to aminoboronic acids.…”

“…Although a series of racemic Bn-TAMs was prepared and their conversion to -aminoboronic acids was demonstrated (Scheme 1), an asymmetric approach was not successful as a consequence of E/Z-isomerism that was observed in Bn-TIMs. 35 Despite significant advances in the area, a need for new synthetic routes that would allow the preparation of chiral Nunprotected -aminoboronic acids exists. Many of the existing methods are either racemic, allow limited scope of substrates, or do not enable the synthesis of N-unprotected derivatives.…”

“…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.…”