Rapid Entry into Biologically Relevant α,α-Difluoroalkylphosphonates Bearing Allyl Protection-Deblocking under Ru(II)/(IV)-Catalysis

Kaushik Panigrahi, Xiang Fei, Masato Kitamura, David B. Berkowitz

Research output: Contribution to journalArticle

Abstract

A convenient synthetic route to α,α-difluoroalkylphosphonates is described. Structurally diverse aldehydes are condensed with LiF2CP(O)(OCH2CH═CH2)2. The resultant alcohols are captured as the pentafluorophenyl thionocarbonates and efficiently deoxygenated with HSnBu3, BEt3, and O2, and then smoothly deblocked with CpRu(IV)(π-allyl)quinoline-2-carboxylate (1-2 mol %) in methanol as an allyl cation scavenger. These mild deprotection conditions provide access to free α,α-difluoroalkylphosphonates in nearly quantitative yield. This methodology is used to rapidly construct new bis-α,α-difluoroalkyl phosphonate inhibitors of PTPIB (protein phosphotyrosine phosphatase-1B).

Original languageEnglish (US)
Pages (from-to)9846-9851
Number of pages6
JournalOrganic Letters
Volume21
Issue number24
DOIs
StatePublished - Dec 20 2019

Fingerprint

Bearings (structural)
Organophosphonates
Protein Tyrosine Phosphatases
phosphatases
Phosphoprotein Phosphatases
quinoline
Catalysis
aldehydes
entry
Aldehydes
inhibitors
carboxylates
catalysis
Methanol
Cations
alcohols
methyl alcohol
routes
Alcohols
methodology

ASJC Scopus subject areas

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Rapid Entry into Biologically Relevant α,α-Difluoroalkylphosphonates Bearing Allyl Protection-Deblocking under Ru(II)/(IV)-Catalysis. / Panigrahi, Kaushik; Fei, Xiang; Kitamura, Masato; Berkowitz, David B.

In: Organic Letters, Vol. 21, No. 24, 20.12.2019, p. 9846-9851.

Research output: Contribution to journalArticle

@article{89bda487b2be422ca37f359e9192fab3,
title = "Rapid Entry into Biologically Relevant α,α-Difluoroalkylphosphonates Bearing Allyl Protection-Deblocking under Ru(II)/(IV)-Catalysis",
abstract = "A convenient synthetic route to α,α-difluoroalkylphosphonates is described. Structurally diverse aldehydes are condensed with LiF2CP(O)(OCH2CH═CH2)2. The resultant alcohols are captured as the pentafluorophenyl thionocarbonates and efficiently deoxygenated with HSnBu3, BEt3, and O2, and then smoothly deblocked with CpRu(IV)(π-allyl)quinoline-2-carboxylate (1-2 mol {\%}) in methanol as an allyl cation scavenger. These mild deprotection conditions provide access to free α,α-difluoroalkylphosphonates in nearly quantitative yield. This methodology is used to rapidly construct new bis-α,α-difluoroalkyl phosphonate inhibitors of PTPIB (protein phosphotyrosine phosphatase-1B).",
author = "Kaushik Panigrahi and Xiang Fei and Masato Kitamura and Berkowitz, {David B.}",
year = "2019",
month = "12",
day = "20",
doi = "10.1021/acs.orglett.9b03707",
language = "English (US)",
volume = "21",
pages = "9846--9851",
journal = "Organic Letters",
issn = "1523-7060",
publisher = "American Chemical Society",
number = "24",

}

TY - JOUR

T1 - Rapid Entry into Biologically Relevant α,α-Difluoroalkylphosphonates Bearing Allyl Protection-Deblocking under Ru(II)/(IV)-Catalysis

AU - Panigrahi, Kaushik

AU - Fei, Xiang

AU - Kitamura, Masato

AU - Berkowitz, David B.

PY - 2019/12/20

Y1 - 2019/12/20

N2 - A convenient synthetic route to α,α-difluoroalkylphosphonates is described. Structurally diverse aldehydes are condensed with LiF2CP(O)(OCH2CH═CH2)2. The resultant alcohols are captured as the pentafluorophenyl thionocarbonates and efficiently deoxygenated with HSnBu3, BEt3, and O2, and then smoothly deblocked with CpRu(IV)(π-allyl)quinoline-2-carboxylate (1-2 mol %) in methanol as an allyl cation scavenger. These mild deprotection conditions provide access to free α,α-difluoroalkylphosphonates in nearly quantitative yield. This methodology is used to rapidly construct new bis-α,α-difluoroalkyl phosphonate inhibitors of PTPIB (protein phosphotyrosine phosphatase-1B).

AB - A convenient synthetic route to α,α-difluoroalkylphosphonates is described. Structurally diverse aldehydes are condensed with LiF2CP(O)(OCH2CH═CH2)2. The resultant alcohols are captured as the pentafluorophenyl thionocarbonates and efficiently deoxygenated with HSnBu3, BEt3, and O2, and then smoothly deblocked with CpRu(IV)(π-allyl)quinoline-2-carboxylate (1-2 mol %) in methanol as an allyl cation scavenger. These mild deprotection conditions provide access to free α,α-difluoroalkylphosphonates in nearly quantitative yield. This methodology is used to rapidly construct new bis-α,α-difluoroalkyl phosphonate inhibitors of PTPIB (protein phosphotyrosine phosphatase-1B).

UR - http://www.scopus.com/inward/record.url?scp=85076235524&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85076235524&partnerID=8YFLogxK

U2 - 10.1021/acs.orglett.9b03707

DO - 10.1021/acs.orglett.9b03707

M3 - Article

C2 - 31789041

AN - SCOPUS:85076235524

VL - 21

SP - 9846

EP - 9851

JO - Organic Letters

JF - Organic Letters

SN - 1523-7060

IS - 24

ER -