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Tetrahedron

Publication date: 2001-01
Volume: 57 Pages: 4793 - 4800
ISSN: 0040-4020, 1464-5416
DOI: 10.1016/S0040-4020(01)00407-0
Publisher: Pergamon Press

Author:

Stevens, CV
Vanderhoydonck, B

Keywords:

acylphosphonates, monochlorination, Baeyer-Villiger oxidation, Science & Technology, Physical Sciences, Chemistry, Organic, Chemistry, DIALKYL ACYLPHOSPHONATES, 0305 Organic Chemistry, 0304 Medicinal and Biomolecular Chemistry, Organic Chemistry

Abstract:

Treatment of diacid dichlorides ClC(:O)CH2(CH2)nCH2C(:O)Cl (n = 1,2,5,8) (I) with tri-Me phosphite or phosphitylation of a diacid HO2C(CH2)6CO2H generates acylphosphonate intermediates; regioselective α-chlorination of the monoacyl phosphonates Me(CH2)nCH2C(:O)P(:O)(OMe)2 (n = 2,7,11,13,15) (II) or diacyl phosphonates derived from I with sulfuryl chloride in the dark followed by removal of the phosphonate moiety with hydrogen peroxide and sodium bicarbonate in methylene chloride (α-chloroacyl phosphonates) or di-Et ether (α,α'-dichlorodiacyl phosphonates) to give α-chloroacid derivs. Me(CH2)nCH(Cl)CO2H (III) or HO2CCH(Cl)(CH2)nCH(Cl)CO2H (IV). E.g., I (n = 8) was treated with tri-Me phosphite neat to give an intermediate bisacyl phosphonate; treatment of the bisacyl phosphonate with neat sulfuryl chloride in the dark for 14 h at room temp. gave the α,α'-dichlorobisacyl diphosphonate which was then deprotected with sodium bicarbonate and hydrogen peroxide to give IV (n = 8) in 79% yield. E.g., II (n = 11) was stirred neat with sulfuryl chloride for 14 h in the dark to give an α-chlorophosphonate deriv. which was deprotected with sodium bicarbonate and hydrogen peroxide to give III (n = 11) in 65% yield. The acyl phosphonate intermediates derived from monocarboxylic acids could also be generated by addn. of tri-Me phosphite to acid chlorides followed by evapn. of the Me chloride byproduct; chlorination with sulfuryl chloride in the dark followed by hydrolysis with hydrogen peroxide and sodium bicarbonate gave α-chlorocarboxylic acids III. The α-chloro acylphosphonate intermediates could also be cleaved by reaction with alcs. or amines to give α-chloro esters and amides in low to moderate yields. E.g., reaction of the α-chloroacyl phosphonate intermediate derived from II (n = 11) with ethanol in methylene chloride for 16 h gave Me(CH2)11CH(Cl)CO2Et in 89% yield, while reaction of the α-chloro acylphosphonate with isopropylamine in dichloromethane gave Me(CH2)11CH(Cl)CONHCHMe3 in 72% yield. The mechanism of cleavage of α-chloro acylphosphonates with sodium bicarbonate and hydrogen peroxide is studied.