Facile Formation of β-Hydroxyboronate Esters by a Cu-Catalyzed Diboration/Matteson Homologation Sequence

Abstract

The copper-catalyzed diboration of aldehydes was used in conjunction with the Matteson homologation, providing the efficient synthesis of β-hydroxyboronate esters. The oxygen-bound boronate ester was found to play a key role in mediating the homologation reaction, which was compared to the α-hydroxyboronate ester (isolated hydrolysis product). The synthetic utility of the diboration/homologation sequence was demonstrated through the oxidation of one product to provide a 1,2-diol.

A Versatile Bis‐Allylboron Reagent for the Stereoselective Synthesis of Chiral Diols

“…! [37] Lastly, the propensity of 3 to form ate complexes was instrumental in increasing the nucleophilicity of the allylboronate and triggering as econd carbonyl addition. Thereaction with the heteroaromatic 3-benzothiophene aldehyde proceeded with excellent stereoselectivity (Table 1, entry 8), while 2-furaldehyde afforded the product with decreased optical purity (72 % ee,T able 1, entry 9).…”

“…[35,36] In this instance,b oric ester 3 acts as an in situ protecting group for the secondary hydroxy group. [37] Lastly, the propensity of 3 to form ate complexes was instrumental in increasing the nucleophilicity of the allylboronate and triggering as econd carbonyl addition. [38] In this reaction, treatment with n-BuLi under Aggarwalsc onditions generated the ate complex, which collapsed to the borinic ester upon trapping of one labile alkoxy substituent with trifluoroacetic anhydride (TFAA).…”

Copper(I)‐Catalyzed Enantioselective Nucleophilic Borylation of Aliphatic Ketones: Synthesis of Enantioenriched Chiral Tertiary α‐Hydroxyboronates

“…[7] Clark and co-workers conducted apioneering study of the catalytic borylation of ketones in 2010, and found that an achiral N-heterocyclic carbene (NHC)/copper(I) complex could be used to catalyze the diboration of various ketones to give the corresponding racemic tertiary a-hydroxyboronates in high yields. [8,9] However,t his work has not yet been extended to the development of an enantioselective process. [10,11] Herein, we report for the first time the enantioselective borylation of the aliphatic ketones 4 with 2 in the presence of ac hiral NHC/copper(I) complex catalyst to give the corresponding chiral tertiary a-hydroxyboronates 5 with moderate to high enantioselectivities (Scheme 1b).Ther esults of an extensive optimization study revealed that 1-cyclohexylethan-1-one (4a)r eacted with 2 (1.1 equiv) in THF at ambient temperature in the presence of CuCl (5 mol %) and an NHC salt, derived from trans-1-amino-2indanol (S,S)-L1 (5 mol %), [12] KOtBu (1.0 equiv), and MeOH (2.0 equiv) as ap roton source,t oa fford the corresponding chiral tertiary a-hydroxyboronate (S)-5a in good yield with high enantioselectivity (Table 1, entry 1).…”

“…[7] Clark and co-workers conducted apioneering study of the catalytic borylation of ketones in 2010, and found that an achiral N-heterocyclic carbene (NHC)/copper(I) complex could be used to catalyze the diboration of various ketones to give the corresponding racemic tertiary a-hydroxyboronates in high yields. [8,9] However,t his work has not yet been extended to the development of an enantioselective process. [10,11] Herein, we report for the first time the enantioselective borylation of the aliphatic ketones 4 with 2 in the presence of ac hiral NHC/copper(I) complex catalyst to give the corresponding chiral tertiary a-hydroxyboronates 5 with moderate to high enantioselectivities (Scheme 1b).…”

Copper(I)‐Catalyzed Enantioselective Nucleophilic Borylation of Aliphatic Ketones: Synthesis of Enantioenriched Chiral Tertiary α‐Hydroxyboronates

“…[6] For example,t ot he best of our knowledge,t here is only one example of catalytic enantioselective arylation of aliphatic ketones to give chiral tertiary alcohols with high enantioselectivity (> 80 % ee). [8,9] However,t his work has not yet been extended to the development of an enantioselective process. [8,9] However,t his work has not yet been extended to the development of an enantioselective process.…”