Enantioselective Electrophilic Cyanation of Boron Enolates: Scope and Mechanistic Studies
Takaya Nagata, Atsuko Tamaki, Kensuke Kiyokawa, Ryosuke Tsutsumi, Masahiro Yamanaka, Satoshi Minakata
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.
Chemistry - A European Journal
https://doi.org/10.1002/chem.201804455
cyanation
enantioselectivity
enolates
synthetic methods
10.1002/chem.201804455
Dive into the research topics of 'Enantioselective Electrophilic Cyanation of Boron Enolates: Scope and Mechanistic Studies'. Together they form a unique fingerprint.
Boron Engineering & Materials Science 100%
Boron Atom Chemical Compounds 76%
Enantioselectivity Engineering & Materials Science 44%
Enantiomers Engineering & Materials Science 38%
Isomers Engineering & Materials Science 32%
Cyanides Engineering & Materials Science 32%
Ketones Engineering & Materials Science 31%
Nuclear magnetic resonance Engineering & Materials Science 26%
Nagata, T., Tamaki, A., Kiyokawa, K., Tsutsumi, R., Yamanaka, M., & Minakata, S. (2018). Enantioselective Electrophilic Cyanation of Boron Enolates: Scope and Mechanistic Studies. Chemistry - A European Journal, 24(64), 17027-17032. https://doi.org/10.1002/chem.201804455
Enantioselective Electrophilic Cyanation of Boron Enolates : Scope and Mechanistic Studies. / Nagata, Takaya; Tamaki, Atsuko; Kiyokawa, Kensuke et al.
In: Chemistry - A European Journal, Vol. 24, No. 64, 16.11.2018, p. 17027-17032.
Nagata, T, Tamaki, A, Kiyokawa, K, Tsutsumi, R, Yamanaka, M & Minakata, S 2018, 'Enantioselective Electrophilic Cyanation of Boron Enolates: Scope and Mechanistic Studies', Chemistry - A European Journal, vol. 24, no. 64, pp. 17027-17032. https://doi.org/10.1002/chem.201804455
Nagata T, Tamaki A, Kiyokawa K, Tsutsumi R, Yamanaka M, Minakata S. Enantioselective Electrophilic Cyanation of Boron Enolates: Scope and Mechanistic Studies. Chemistry - A European Journal. 2018 Nov 16;24(64):17027-17032. doi: 10.1002/chem.201804455
Nagata, Takaya ; Tamaki, Atsuko ; Kiyokawa, Kensuke et al. / Enantioselective Electrophilic Cyanation of Boron Enolates : Scope and Mechanistic Studies. In: Chemistry - A European Journal. 2018 ; Vol. 24, No. 64. pp. 17027-17032.
@article{4e578f12d0ab4cceada1989c379a2299,
title = "Enantioselective Electrophilic Cyanation of Boron Enolates: Scope and Mechanistic Studies",
abstract = "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.",
keywords = "boron, cyanation, enantioselectivity, enolates, synthetic methods",
author = "Takaya Nagata and Atsuko Tamaki and Kensuke Kiyokawa and Ryosuke Tsutsumi and Masahiro Yamanaka and Satoshi Minakata",
note = "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: {\textcopyright} 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim",
doi = "10.1002/chem.201804455",
journal = "Chemistry - A European Journal",
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
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
U2 - 10.1002/chem.201804455
DO - 10.1002/chem.201804455
JO - Chemistry - A European Journal
JF - Chemistry - A European Journal