Benzothiazoline: Versatile hydrogen donor for organocatalytic transfer hydrogenation

Chen Zhu, Kodai Saito, Masahiro Yamanaka, Takahiko Akiyama

Research output: Contribution to journalArticle

78 Citations (Scopus)

Abstract

ConspectusThe asymmetric reduction of ketimines is an important method for the preparation of amines in optically pure form. Inspired by the biological system using NAD(P)H, Hantzsch ester has been extensively employed as a hydrogen donor in combination with chiral phosphoric acid for the transfer hydrogenation of ketimines to furnish amines with high to excellent enantioselectivities.We focused on 2-substituted benzothiazoline as a hydrogen donor in the phosphoric acid catalyzed transfer hydrogenation reaction of ketimines for the following reasons: (1) benzothiazoline is readily prepared just by mixing 2-aminobenzenethiol and aldehyde, (2) both reactivity (hydrogen donating ability) and enantioselectivity would be controlled by tuning the 2-substituent of benzothiazoline, and (3) benzothiazoline can be stored in a refrigerator under inert atmosphere without conceivable decomposition. Both the 2-position of benzothiazoline and the 3,3′-position of phosphoric acid are tunable in order to achieve excellent enantioselectivity.Benzothiazoline proved to be useful hydrogen donor in combination with chiral phosphoric acid for the transfer hydrogenation reaction of ketimine derivatives to afford the corresponding amines with high to excellent enantioselectivities by tuning the 2-substituent of benzothiazoline. Ketimines derived from acetophenone, propiophenone, α-keto ester, trifluoromethyl ketone, and difluoromethyl ketone derivatives proved to be suitable substrates. Benzothiazoline could be generated in situ starting from 2-aminobenzenethiol and aromatic aldehyde in the presence of ketimine and chiral phosphoric acid and successfully worked in the sequential transfer hydrogenation reaction. The reductive amination of dialkyl ketones also proceeded with high enantioselectivities. Use of 2-deuterated benzothiazoline led to the formation of α-deuterated amines with excellent enantioselectivities. The kinetic isotope effect (kH/kC = 3.8) was observed in the competitive reaction between H- and D-benzothiazoline, which explicitly implies that the cleavage of the C-H (C-D) bond is the rate-determining step in the transfer hydrogenation reaction.Benzothiazoline yielded products with higher enantioselectivity in the transfer hydrogenation reaction of ketimines, particularly ketimines derived from propiophenone derivatives, than Hantzsch ester. DFT study elucidated the mechanism, as well as the difference in selectivity, between benzothiazoline and Hantzsch ester. The chiral phosphoric acid activates ketimines and benzothiazoline by means of the Brønsted acidic site (proton) and the Brønsted basic site (phosphoryl oxygen), respectively, to accelerate the hydride transfer reaction.

Original languageEnglish
Pages (from-to)388-398
Number of pages11
JournalAccounts of Chemical Research
Volume48
Issue number2
DOIs
Publication statusPublished - 2015 Feb 17
Externally publishedYes

Fingerprint

Hydrogenation
Hydrogen
Enantioselectivity
Amines
Propiophenones
Esters
Ketones
Derivatives
Aldehydes
benzothiazoline
Tuning
ketimine
Amination
Refrigerators
Biological systems
Discrete Fourier transforms
Hydrides
Isotopes
NAD
phosphoric acid

ASJC Scopus subject areas

  • Chemistry(all)

Cite this

Benzothiazoline : Versatile hydrogen donor for organocatalytic transfer hydrogenation. / Zhu, Chen; Saito, Kodai; Yamanaka, Masahiro; Akiyama, Takahiko.

In: Accounts of Chemical Research, Vol. 48, No. 2, 17.02.2015, p. 388-398.

Research output: Contribution to journalArticle

Zhu, Chen ; Saito, Kodai ; Yamanaka, Masahiro ; Akiyama, Takahiko. / Benzothiazoline : Versatile hydrogen donor for organocatalytic transfer hydrogenation. In: Accounts of Chemical Research. 2015 ; Vol. 48, No. 2. pp. 388-398.
@article{bff87655782f40d2a62ac3f2e81e69a9,
title = "Benzothiazoline: Versatile hydrogen donor for organocatalytic transfer hydrogenation",
abstract = "ConspectusThe asymmetric reduction of ketimines is an important method for the preparation of amines in optically pure form. Inspired by the biological system using NAD(P)H, Hantzsch ester has been extensively employed as a hydrogen donor in combination with chiral phosphoric acid for the transfer hydrogenation of ketimines to furnish amines with high to excellent enantioselectivities.We focused on 2-substituted benzothiazoline as a hydrogen donor in the phosphoric acid catalyzed transfer hydrogenation reaction of ketimines for the following reasons: (1) benzothiazoline is readily prepared just by mixing 2-aminobenzenethiol and aldehyde, (2) both reactivity (hydrogen donating ability) and enantioselectivity would be controlled by tuning the 2-substituent of benzothiazoline, and (3) benzothiazoline can be stored in a refrigerator under inert atmosphere without conceivable decomposition. Both the 2-position of benzothiazoline and the 3,3′-position of phosphoric acid are tunable in order to achieve excellent enantioselectivity.Benzothiazoline proved to be useful hydrogen donor in combination with chiral phosphoric acid for the transfer hydrogenation reaction of ketimine derivatives to afford the corresponding amines with high to excellent enantioselectivities by tuning the 2-substituent of benzothiazoline. Ketimines derived from acetophenone, propiophenone, α-keto ester, trifluoromethyl ketone, and difluoromethyl ketone derivatives proved to be suitable substrates. Benzothiazoline could be generated in situ starting from 2-aminobenzenethiol and aromatic aldehyde in the presence of ketimine and chiral phosphoric acid and successfully worked in the sequential transfer hydrogenation reaction. The reductive amination of dialkyl ketones also proceeded with high enantioselectivities. Use of 2-deuterated benzothiazoline led to the formation of α-deuterated amines with excellent enantioselectivities. The kinetic isotope effect (kH/kC = 3.8) was observed in the competitive reaction between H- and D-benzothiazoline, which explicitly implies that the cleavage of the C-H (C-D) bond is the rate-determining step in the transfer hydrogenation reaction.Benzothiazoline yielded products with higher enantioselectivity in the transfer hydrogenation reaction of ketimines, particularly ketimines derived from propiophenone derivatives, than Hantzsch ester. DFT study elucidated the mechanism, as well as the difference in selectivity, between benzothiazoline and Hantzsch ester. The chiral phosphoric acid activates ketimines and benzothiazoline by means of the Br{\o}nsted acidic site (proton) and the Br{\o}nsted basic site (phosphoryl oxygen), respectively, to accelerate the hydride transfer reaction.",
author = "Chen Zhu and Kodai Saito and Masahiro Yamanaka and Takahiko Akiyama",
year = "2015",
month = "2",
day = "17",
doi = "10.1021/ar500414x",
language = "English",
volume = "48",
pages = "388--398",
journal = "Accounts of Chemical Research",
issn = "0001-4842",
publisher = "American Chemical Society",
number = "2",

}

TY - JOUR

T1 - Benzothiazoline

T2 - Versatile hydrogen donor for organocatalytic transfer hydrogenation

AU - Zhu, Chen

AU - Saito, Kodai

AU - Yamanaka, Masahiro

AU - Akiyama, Takahiko

PY - 2015/2/17

Y1 - 2015/2/17

N2 - ConspectusThe asymmetric reduction of ketimines is an important method for the preparation of amines in optically pure form. Inspired by the biological system using NAD(P)H, Hantzsch ester has been extensively employed as a hydrogen donor in combination with chiral phosphoric acid for the transfer hydrogenation of ketimines to furnish amines with high to excellent enantioselectivities.We focused on 2-substituted benzothiazoline as a hydrogen donor in the phosphoric acid catalyzed transfer hydrogenation reaction of ketimines for the following reasons: (1) benzothiazoline is readily prepared just by mixing 2-aminobenzenethiol and aldehyde, (2) both reactivity (hydrogen donating ability) and enantioselectivity would be controlled by tuning the 2-substituent of benzothiazoline, and (3) benzothiazoline can be stored in a refrigerator under inert atmosphere without conceivable decomposition. Both the 2-position of benzothiazoline and the 3,3′-position of phosphoric acid are tunable in order to achieve excellent enantioselectivity.Benzothiazoline proved to be useful hydrogen donor in combination with chiral phosphoric acid for the transfer hydrogenation reaction of ketimine derivatives to afford the corresponding amines with high to excellent enantioselectivities by tuning the 2-substituent of benzothiazoline. Ketimines derived from acetophenone, propiophenone, α-keto ester, trifluoromethyl ketone, and difluoromethyl ketone derivatives proved to be suitable substrates. Benzothiazoline could be generated in situ starting from 2-aminobenzenethiol and aromatic aldehyde in the presence of ketimine and chiral phosphoric acid and successfully worked in the sequential transfer hydrogenation reaction. The reductive amination of dialkyl ketones also proceeded with high enantioselectivities. Use of 2-deuterated benzothiazoline led to the formation of α-deuterated amines with excellent enantioselectivities. The kinetic isotope effect (kH/kC = 3.8) was observed in the competitive reaction between H- and D-benzothiazoline, which explicitly implies that the cleavage of the C-H (C-D) bond is the rate-determining step in the transfer hydrogenation reaction.Benzothiazoline yielded products with higher enantioselectivity in the transfer hydrogenation reaction of ketimines, particularly ketimines derived from propiophenone derivatives, than Hantzsch ester. DFT study elucidated the mechanism, as well as the difference in selectivity, between benzothiazoline and Hantzsch ester. The chiral phosphoric acid activates ketimines and benzothiazoline by means of the Brønsted acidic site (proton) and the Brønsted basic site (phosphoryl oxygen), respectively, to accelerate the hydride transfer reaction.

AB - ConspectusThe asymmetric reduction of ketimines is an important method for the preparation of amines in optically pure form. Inspired by the biological system using NAD(P)H, Hantzsch ester has been extensively employed as a hydrogen donor in combination with chiral phosphoric acid for the transfer hydrogenation of ketimines to furnish amines with high to excellent enantioselectivities.We focused on 2-substituted benzothiazoline as a hydrogen donor in the phosphoric acid catalyzed transfer hydrogenation reaction of ketimines for the following reasons: (1) benzothiazoline is readily prepared just by mixing 2-aminobenzenethiol and aldehyde, (2) both reactivity (hydrogen donating ability) and enantioselectivity would be controlled by tuning the 2-substituent of benzothiazoline, and (3) benzothiazoline can be stored in a refrigerator under inert atmosphere without conceivable decomposition. Both the 2-position of benzothiazoline and the 3,3′-position of phosphoric acid are tunable in order to achieve excellent enantioselectivity.Benzothiazoline proved to be useful hydrogen donor in combination with chiral phosphoric acid for the transfer hydrogenation reaction of ketimine derivatives to afford the corresponding amines with high to excellent enantioselectivities by tuning the 2-substituent of benzothiazoline. Ketimines derived from acetophenone, propiophenone, α-keto ester, trifluoromethyl ketone, and difluoromethyl ketone derivatives proved to be suitable substrates. Benzothiazoline could be generated in situ starting from 2-aminobenzenethiol and aromatic aldehyde in the presence of ketimine and chiral phosphoric acid and successfully worked in the sequential transfer hydrogenation reaction. The reductive amination of dialkyl ketones also proceeded with high enantioselectivities. Use of 2-deuterated benzothiazoline led to the formation of α-deuterated amines with excellent enantioselectivities. The kinetic isotope effect (kH/kC = 3.8) was observed in the competitive reaction between H- and D-benzothiazoline, which explicitly implies that the cleavage of the C-H (C-D) bond is the rate-determining step in the transfer hydrogenation reaction.Benzothiazoline yielded products with higher enantioselectivity in the transfer hydrogenation reaction of ketimines, particularly ketimines derived from propiophenone derivatives, than Hantzsch ester. DFT study elucidated the mechanism, as well as the difference in selectivity, between benzothiazoline and Hantzsch ester. The chiral phosphoric acid activates ketimines and benzothiazoline by means of the Brønsted acidic site (proton) and the Brønsted basic site (phosphoryl oxygen), respectively, to accelerate the hydride transfer reaction.

UR - http://www.scopus.com/inward/record.url?scp=84923068811&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84923068811&partnerID=8YFLogxK

U2 - 10.1021/ar500414x

DO - 10.1021/ar500414x

M3 - Article

C2 - 25611073

AN - SCOPUS:84923068811

VL - 48

SP - 388

EP - 398

JO - Accounts of Chemical Research

JF - Accounts of Chemical Research

SN - 0001-4842

IS - 2

ER -