Copper(I)-Catalyzed Enantioselective Synthesis of α-Chiral Linear or Carbocyclic (E)-(γ-Alkoxyallyl)boronates

Abstract

A new method has been developed for the catalytic asymmetric synthesis of α-chiral linear or carbocyclic (γ-alkoxyallyl)boronates via the copper(I)-catalyzed γ-boryl substitution of allyl acetals. This reaction afforded the products in high yields with excellent E:Z selectivities and enantioselectivities [only (E)-product, 91-98% ee] and also exhibited high functional group compatibility. Subsequent allylation of aldehydes with the α-chiral (γ-alkoxyallyl)boronates provided the anti-1,2-diol derivatives in a highly stereospecific manner, and the utility of the α-chiral (γ-alkoxyallyl)boronates was further demonstrated by a convergent coupling of a complex polyol derivative using a (γ-alkoxyallyl)boronate and a chiral α-oxyaldehyde. The stereoselective modular construction of a complex 3,3-disubstituted cyclopentene containing three consecutive stereocenters including a quaternary chiral carbon was also reported. Useful transformations of the α-chiral linear (γ-alkoxyallyl)boronates were also demonstrated.

Asymmetric Synthesis of Secondary and Tertiary Boronic Esters

“…Ito later extended this process to the g substitution of allyl acetals,providing access to a-chiral g-alkoxyallyl boronic esters. [83] In 2010, Hoveyda and co-workers reported an NHC-copper-catalysed borylation of allylic carbonates. [84] Importantly,t his process provided the allyl boronic esters with excellent ee values when either the E-o rZ carbonates were used (providing the allyl boronic esters with opposite absolute stereochemistry).…”

A mild copper catalyzed method for the selective deprotection of aryl allyl ethers

“…Similar copper boryl reagent combinations to those described in this report have been shown to promote a diverse array of transformations, including the hydroboration of alkenes and alkynes, [12][13][14][15][16] the borylation of aldehydes and imines, β-borylation of α,β-unsaturated carbonyl compounds 13,[17][18][19][20][21] and a variety of C-X borylations to generate aryl, alkyl and allyl boronates. 11,[22][23][24][25][26][27][28] Of these, the current reaction has closest parallels with the last of these transformations for which an S N 2' type displacement is commonly invoked. 29 In line with this, GCMS analysis of the crude reaction mixture reveals the presence of a signal with m/z = 168 corresponding to the formation of allyl-Bpin as a byproduct.…”

Copper‐Catalyzed Asymmetric Borylative Cyclization of Cyclohexadienone‐Containing 1,6‐Dienes

“…[14] Thus, the insertion of terminal alkene to CuÀ B consequently occurs first and places the B at the less hindered site of the alkene to form an stereospecific secondary alkylcopper intermediate T2 (Scheme 1c). [15] This regioselectivity is probably caused by the stereoelectronic effect that stabilizes the σ (CuÀ C) bond through interaction with the σ* (CÀ O) bond. The second issue is that the easily-occurred β-oxygen elimination of alkylcopper intermediate should be avoided.…”

“…Indeed, this side reaction does not take place, because the alkylcopper intermediate could be quickly trapped by the highly reactive cyclohexadienone. [15,16] The third issue is the enantioselective controls: one is the addition of a boryl-copper species to the electron-rich alkene (high LUMO); and the other is the conjugate addition of a alkyl-copper intermediate to the electron-deficient alkene, cyclohexadienone (low LUMO). [16,17] Obviously, the required electronic properties of chiral copper catalyst are quite different in these two processes.…”