Two step synthesis of acyltrifluorobronate from aldehydes mediated by angelw: Cu (I)

As an important synthon in organic synthesis, organoboron compounds are widely used in organic chemistry and drug synthesis Since Nozaki et al First realized the separation of acylborides by the reaction of lithium borate with benzoyl chloride in 2007, chemists have carried out many researches on the synthesis and reactivity of acylborides Among them, potassium acyltrifluorborate (Kats) has attracted much attention because of its unique reactivity and remarkable stability to air and water At present, the synthesis of these compounds involves many complicated steps and is not economical Dumas developed a method for the synthesis of Kats (scheme 1AA) by lithium of benzotriazolyl n, o-acetals in 2012 Hajime ITO and Perrin team reported the method of synthesizing acyl Mida borate by ozone decomposition and dihydroxylation / oxidative cracking of alkenyl Mida borate (scheme 1BA) Yudin et al Reported the method of synthesizing acyl Mida borate by DESs Martin oxidation of α - hydroxy Mida borate (scheme 1BB) Although these three synthesis strategies have mild conditions, they can be used for the preparation of highly functional acyl borates, but they still need more complicated operations Therefore, it is necessary to develop a new, efficient, simple and environmentally friendly synthesis method of potassium acyltrifluorborate (Kats) Recently, the research group of Professor Hajime Ito of Hokkaido University proposed a new strategy (scheme 1c) to prepare α - hydroxyborate from aldehyde catalyzed by Cu (I), then α - hydroxyborate was transformed into α - hydroxytrifluoroaborate by khf 2, and then Kats was synthesized by 9-azaadamantane-n-oxygen free radical (nor azado) or DMSO / AC 2O oxidation of α - hydroxytrifluoroaborate This Mida free method reduces the synthesis steps and is suitable for a variety of functional groups It provides a simple and effective method for the synthesis of Kats Relevant research results were published in angelw Chem Int ed (DOI: 10.1002 / anie 201901748) (picture source: angelw Chem Int ed.) firstly, the author synthesized α - hydroxytrifluoroaborate 1a by Cu (I) catalytic one pot method, and then prepared acyl trifluoroaborate by oxidation of 1a Based on this, the author optimized the oxidation conditions (Table 1) When DMSO / AC 2O and nor azado / nano 2 / AcOH were added, the reaction energy was obtained by 85% and 92% respectively Therefore, the best oxidation condition is DMSO / AC 2O or nor azado (picture source: angelw Chem Int ed.) next, based on two oxidation conditions: I) DMSO / AC 2O and II) nor azado, the author studied the substrate range of the reaction (scheme 2) The results show that the reaction has good functional group tolerance, and the corresponding Kats products can be obtained in good yields when the substrate is aromatic substituted alcohol, heteroaryl substituted alcohol, alkyl substituted alcohol, sterically hindered substituted alcohol or even glucose substituted alcohol (image source: angelw Chem Int ed.) in order to prove the practicability and effectiveness of the synthesis strategy, the author studied the synthesis of α - amino acid derived Kats (Table 2) The results show that nor azado can efficiently oxidize α - hydroxytrifluoroaborate 3a, which is obtained by boronization of n-cbz-glycine catalyzed by Cu (I), and generate corresponding kat4a Then, we also studied the synthesis of Kats derived from amino acid analogs enriched with enantiomers It was found that for the aldehydes derived from n-boc-phenylalanine 3b, n-fmoc-leucine 3C and n-cbz-valine 3D, the corresponding Kats products could be obtained with high yield and high enantiomeric purity The synthesis of 2C and 4B proves that the strategy can be applied to the gram scale synthesis of Kats without the loss of enantiomeric purity of chiral alcohols (scheme 3) (picture source: angelw Chem Int ed.) (picture source: angelw Chem Int ed.): the author has developed a new strategy for preparing Kats from aldehydes in two steps The strategy is not only easy to operate, but also suitable for scale-up The reaction conditions are mild, with high-level tolerance More importantly, the synthesis of Kats derived from natural α - aminoaldehydes without loss of enantiomeric purity has greatly expanded the application of the synthesis strategy.