TY - JOUR
T1 - Enantioselective Electrophilic Cyanation of Boron Enolates
T2 - Scope and Mechanistic Studies
AU - Nagata, Takaya
AU - Tamaki, Atsuko
AU - Kiyokawa, Kensuke
AU - Tsutsumi, Ryosuke
AU - Yamanaka, Masahiro
AU - Minakata, Satoshi
N1 - Funding Information:
This work was supported by JSPS KAKENHI Grant Numbers JP18J10497 (T.N.), JP18K14217 (K.K.), and JP17KT0011 (M.Y.). We thank Dr. Norimitsu Tohnai (Osaka University) for assistance with the X-ray crystallographic analysis.
Publisher Copyright:
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2018/11/16
Y1 - 2018/11/16
N2 - Chiral β-ketonitriles bearing a stereogenic carbon center at the α-position are an important class of compounds, many of which serve as useful synthetic intermediates for the preparation of chiral 1,3-aminoalcohols, β-hydroxy nitriles, and related derivatives. Although the enantioselective electrophilic cyanation of enolate equivalents is one of the most promising approaches for the synthesis of chiral β-ketonitriles, the available methods are largely limited to reactions of 1,3-dicarbonyl compounds. Herein, we report on enantioselective electrophilic cyanation of boron enolates, which are readily prepared from α,β-unsaturated ketones and diisopinocampheylborane (Ipc2BH) to afford chiral β-ketonitriles with a high level of enantioselectivity. The present method is scalable and provides facile access to both enantiomers of chiral β-ketonitriles. Analysis of the in situ generated boron enolates by NMR revealed that hydroboration proceeds in a stereospecific manner, providing α,α-disubstituted boron enolates in the form of single isomers. Furthermore, the results of DFT calculations suggest that the cyanation of the boron enolates with p-toluenesulfonyl cyanide (TsCN) proceeds in a highly enantioselective manner through a unique six-membered ring transition state.
AB - Chiral β-ketonitriles bearing a stereogenic carbon center at the α-position are an important class of compounds, many of which serve as useful synthetic intermediates for the preparation of chiral 1,3-aminoalcohols, β-hydroxy nitriles, and related derivatives. Although the enantioselective electrophilic cyanation of enolate equivalents is one of the most promising approaches for the synthesis of chiral β-ketonitriles, the available methods are largely limited to reactions of 1,3-dicarbonyl compounds. Herein, we report on enantioselective electrophilic cyanation of boron enolates, which are readily prepared from α,β-unsaturated ketones and diisopinocampheylborane (Ipc2BH) to afford chiral β-ketonitriles with a high level of enantioselectivity. The present method is scalable and provides facile access to both enantiomers of chiral β-ketonitriles. Analysis of the in situ generated boron enolates by NMR revealed that hydroboration proceeds in a stereospecific manner, providing α,α-disubstituted boron enolates in the form of single isomers. Furthermore, the results of DFT calculations suggest that the cyanation of the boron enolates with p-toluenesulfonyl cyanide (TsCN) proceeds in a highly enantioselective manner through a unique six-membered ring transition state.
KW - boron
KW - cyanation
KW - enantioselectivity
KW - enolates
KW - synthetic methods
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U2 - 10.1002/chem.201804455
DO - 10.1002/chem.201804455
M3 - Article
C2 - 30256466
AN - SCOPUS:85056592714
VL - 24
SP - 17027
EP - 17032
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal
SN - 0947-6539
IS - 64
ER -