A novel, highly enantioselective ketone alkynylation reaction mediated by chiral zinc aminoalkoxides

Lushi Tan; Cheng Yi Chen; Richard D. Tillyer; Edward J.J. Grabowski; Paul J. Reider

doi:10.1002/(SICI)1521-3773(19990301)38:5<711::AID-ANIE711>3.0.CO;2-W

A novel, highly enantioselective ketone alkynylation reaction mediated by chiral zinc aminoalkoxides

Lushi Tan
, Cheng Yi Chen
, Richard D. Tillyer
, Edward J.J. Grabowski
, Paul J. Reider

Research output: Contribution to journal › Article › peer-review

219 Scopus citations

Abstract

Kilogram-scale synthesis of the HIV reverse transcriptase inhibitor efavirenz was achieved by means of a highly enantioselective alkynylation of prochiral ketones 1 with alkynyllithium or alkynylmagnesium reagents in the presence of chiral zinc aminoalkoxides as mediators. With the achiral auxiliary 2,2,2-trifluoroethanol (R³=CF₃CH₂), the efavirenz precursor 2 (R¹ =H, R²=cyclopropyl) was obtained with an ee of 99.2%.

Original language	English (US)
Pages (from-to)	711-713
Number of pages	3
Journal	Angewandte Chemie - International Edition
Volume	38
Issue number	5
DOIs	https://doi.org/10.1002/(SICI)1521-3773(19990301)38:5<711::AID-ANIE711>3.0.CO;2-W
State	Published - Mar 1 1999
Externally published	Yes

All Science Journal Classification (ASJC) codes

Catalysis
General Chemistry

Keywords

Alkynylations
Amino alcohols
Ketones
Nucleophilic additions
Zinc

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10.1002/(SICI)1521-3773(19990301)38:5<711::AID-ANIE711>3.0.CO;2-W

Cite this

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title = "A novel, highly enantioselective ketone alkynylation reaction mediated by chiral zinc aminoalkoxides",

abstract = "Kilogram-scale synthesis of the HIV reverse transcriptase inhibitor efavirenz was achieved by means of a highly enantioselective alkynylation of prochiral ketones 1 with alkynyllithium or alkynylmagnesium reagents in the presence of chiral zinc aminoalkoxides as mediators. With the achiral auxiliary 2,2,2-trifluoroethanol (R3=CF3CH2), the efavirenz precursor 2 (R1 =H, R2=cyclopropyl) was obtained with an ee of 99.2\%.",

keywords = "Alkynylations, Amino alcohols, Ketones, Nucleophilic additions, Zinc",

author = "Lushi Tan and Chen, \{Cheng Yi\} and Tillyer, \{Richard D.\} and Grabowski, \{Edward J.J.\} and Reider, \{Paul J.\}",

year = "1999",

month = mar,

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doi = "10.1002/(SICI)1521-3773(19990301)38:5<711::AID-ANIE711>3.0.CO;2-W",

language = "English (US)",

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pages = "711--713",

journal = "Angewandte Chemie - International Edition",

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publisher = "John Wiley and Sons Ltd",

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}

TY - JOUR

T1 - A novel, highly enantioselective ketone alkynylation reaction mediated by chiral zinc aminoalkoxides

AU - Tan, Lushi

AU - Chen, Cheng Yi

AU - Tillyer, Richard D.

AU - Grabowski, Edward J.J.

AU - Reider, Paul J.

PY - 1999/3/1

Y1 - 1999/3/1

N2 - Kilogram-scale synthesis of the HIV reverse transcriptase inhibitor efavirenz was achieved by means of a highly enantioselective alkynylation of prochiral ketones 1 with alkynyllithium or alkynylmagnesium reagents in the presence of chiral zinc aminoalkoxides as mediators. With the achiral auxiliary 2,2,2-trifluoroethanol (R3=CF3CH2), the efavirenz precursor 2 (R1 =H, R2=cyclopropyl) was obtained with an ee of 99.2%.

AB - Kilogram-scale synthesis of the HIV reverse transcriptase inhibitor efavirenz was achieved by means of a highly enantioselective alkynylation of prochiral ketones 1 with alkynyllithium or alkynylmagnesium reagents in the presence of chiral zinc aminoalkoxides as mediators. With the achiral auxiliary 2,2,2-trifluoroethanol (R3=CF3CH2), the efavirenz precursor 2 (R1 =H, R2=cyclopropyl) was obtained with an ee of 99.2%.

KW - Alkynylations

KW - Amino alcohols

KW - Ketones

KW - Nucleophilic additions

KW - Zinc

UR - https://www.scopus.com/pages/publications/0033105506

UR - https://www.scopus.com/pages/publications/0033105506#tab=citedBy

U2 - 10.1002/(SICI)1521-3773(19990301)38:5<711::AID-ANIE711>3.0.CO;2-W

DO - 10.1002/(SICI)1521-3773(19990301)38:5<711::AID-ANIE711>3.0.CO;2-W

M3 - Article

AN - SCOPUS:0033105506

SN - 1433-7851

VL - 38

SP - 711

EP - 713

JO - Angewandte Chemie - International Edition

JF - Angewandte Chemie - International Edition

IS - 5

ER -

A novel, highly enantioselective ketone alkynylation reaction mediated by chiral zinc aminoalkoxides

Abstract

All Science Journal Classification (ASJC) codes

Keywords

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