Ruthenium-Catalyzed Asymmetric Allylic Alkylation of Isatins

Barry M. Trost; Christopher A. Kalnmals; Divya Ramakrishnan; Michael C. Ryan; Rebecca W. Smaha; Sean Parkin

doi:10.1021/acs.orglett.0c00504

Ruthenium-Catalyzed Asymmetric Allylic Alkylation of Isatins

Barry M. Trost, Christopher A. Kalnmals, Divya Ramakrishnan, Michael C. Ryan, Rebecca W. Smaha, Sean Parkin

Chemistry

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

12 Scopus citations

Abstract

A new ruthenium-based catalytic system for branched-selective asymmetric allylic alkylation is disclosed and applied to the synthesis of chiral isatin derivatives. The catalyst, which is generated in situ from commercially available CpRu(MeCN)₃PF₆ and a BINOL-derived phosphoramidite, is both highly active (TON up to 180) and insensitive to air and moisture. Additionally, the N-alkylated isatins accessible using this methodology are versatile building blocks that are readily transformed into chiral analogs of achiral drug molecules.

Original language	English
Pages (from-to)	2584-2589
Number of pages	6
Journal	Organic Letters
Volume	22
Issue number	7
DOIs	https://doi.org/10.1021/acs.orglett.0c00504
State	Published - Apr 3 2020

Bibliographical note

Funding Information:
We thank the Tamaki Foundation and Chugai Pharmaceuticals for their generous partial financial support of our program. Part of this work was performed at the Stanford Nano Shared Facilities (SNSF), supported by the National Science Foundation under Award ECCS-1542152. D.R. thanks Stanford Chemistry for two Undergraduate Summer Research Fellowships. We also thank Dr. Elumalai Gnanamani (Stanford University) and Dr. Jana Maclaren (Stanford University) for assistance in obtaining a crystal structure of 9mj .

Publisher Copyright:
Copyright © 2020 American Chemical Society.

ASJC Scopus subject areas

Biochemistry
Physical and Theoretical Chemistry
Organic Chemistry

Access to Document

10.1021/acs.orglett.0c00504

Cite this

@article{e9b222076f604355b5940087d818e8ea,

title = "Ruthenium-Catalyzed Asymmetric Allylic Alkylation of Isatins",

abstract = "A new ruthenium-based catalytic system for branched-selective asymmetric allylic alkylation is disclosed and applied to the synthesis of chiral isatin derivatives. The catalyst, which is generated in situ from commercially available CpRu(MeCN)3PF6 and a BINOL-derived phosphoramidite, is both highly active (TON up to 180) and insensitive to air and moisture. Additionally, the N-alkylated isatins accessible using this methodology are versatile building blocks that are readily transformed into chiral analogs of achiral drug molecules.",

author = "Trost, {Barry M.} and Kalnmals, {Christopher A.} and Divya Ramakrishnan and Ryan, {Michael C.} and Smaha, {Rebecca W.} and Sean Parkin",

note = "Funding Information: We thank the Tamaki Foundation and Chugai Pharmaceuticals for their generous partial financial support of our program. Part of this work was performed at the Stanford Nano Shared Facilities (SNSF), supported by the National Science Foundation under Award ECCS-1542152. D.R. thanks Stanford Chemistry for two Undergraduate Summer Research Fellowships. We also thank Dr. Elumalai Gnanamani (Stanford University) and Dr. Jana Maclaren (Stanford University) for assistance in obtaining a crystal structure of 9mj . Publisher Copyright: Copyright {\textcopyright} 2020 American Chemical Society.",

year = "2020",

month = apr,

day = "3",

doi = "10.1021/acs.orglett.0c00504",

language = "English",

volume = "22",

pages = "2584--2589",

number = "7",

}

TY - JOUR

T1 - Ruthenium-Catalyzed Asymmetric Allylic Alkylation of Isatins

AU - Trost, Barry M.

AU - Kalnmals, Christopher A.

AU - Ramakrishnan, Divya

AU - Ryan, Michael C.

AU - Smaha, Rebecca W.

AU - Parkin, Sean

N1 - Funding Information: We thank the Tamaki Foundation and Chugai Pharmaceuticals for their generous partial financial support of our program. Part of this work was performed at the Stanford Nano Shared Facilities (SNSF), supported by the National Science Foundation under Award ECCS-1542152. D.R. thanks Stanford Chemistry for two Undergraduate Summer Research Fellowships. We also thank Dr. Elumalai Gnanamani (Stanford University) and Dr. Jana Maclaren (Stanford University) for assistance in obtaining a crystal structure of 9mj . Publisher Copyright: Copyright © 2020 American Chemical Society.

PY - 2020/4/3

Y1 - 2020/4/3

N2 - A new ruthenium-based catalytic system for branched-selective asymmetric allylic alkylation is disclosed and applied to the synthesis of chiral isatin derivatives. The catalyst, which is generated in situ from commercially available CpRu(MeCN)3PF6 and a BINOL-derived phosphoramidite, is both highly active (TON up to 180) and insensitive to air and moisture. Additionally, the N-alkylated isatins accessible using this methodology are versatile building blocks that are readily transformed into chiral analogs of achiral drug molecules.

AB - A new ruthenium-based catalytic system for branched-selective asymmetric allylic alkylation is disclosed and applied to the synthesis of chiral isatin derivatives. The catalyst, which is generated in situ from commercially available CpRu(MeCN)3PF6 and a BINOL-derived phosphoramidite, is both highly active (TON up to 180) and insensitive to air and moisture. Additionally, the N-alkylated isatins accessible using this methodology are versatile building blocks that are readily transformed into chiral analogs of achiral drug molecules.

UR - http://www.scopus.com/inward/record.url?scp=85082519349&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85082519349&partnerID=8YFLogxK

U2 - 10.1021/acs.orglett.0c00504

DO - 10.1021/acs.orglett.0c00504

M3 - Article

C2 - 32202122

AN - SCOPUS:85082519349

SN - 1523-7060

VL - 22

SP - 2584

EP - 2589

JO - Organic Letters

JF - Organic Letters

IS - 7

ER -

Ruthenium-Catalyzed Asymmetric Allylic Alkylation of Isatins

Abstract

Bibliographical note

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this