Stereochemical Studies of the Opening of Chloro Vinyl Epoxides: Cyclic Chloronium Ions as Intermediates

Abstract

A systematic study of the opening of a collection of chlorinated vinyl epoxides is reported, which includes experiments that implicate both five- and four-membered chloronium ions as plausible intermediates in this type of epoxide opening reaction.

Stereoselective Halogenation in Natural Product Synthesis

“…[32] Carreira and co-workers recently performed a careful mechanistic study, implicating the likely intermediacy of the four-membered ring cyclic chloronium ion ( 67 ) rather than the five-membered ring isomer. [33] …”

“…Thes tereoselective preparation of propargylic alcohol substrates is not always straightforward. When Crimmins and co-workers attempted the direct conversion of the aldehyde 28 to the propagylic alcohol 31 for the synthesis of (À)isolaurallene (33), the carbonyl addition of ethynylmagnesium bromide was unselective (Scheme 4). [17] Precedent suggests that the use of at itanium acetylide reagent would favor formation of the undesired diastereomer.T hus,t he requisite intermediate 31 was prepared in adiastereomerically pure form via alonger sequence including Wittig olefination, Sharpless asymmetric epoxidation, and elimination of ac hloroepoxide intermediate 30.T hen, 31 was transformed to the desired bromoallene 32 following Overmans procedure (8:1 dr, 9% S N 2).…”

“…[32] Carreira and co-workers recently performed ac areful mechanistic study,i mplicating the likely intermediacyo ft he four-membered ring cyclic chloronium ion (67)r ather than the five-membered ring isomer. [33] Openings of other types of reactive three-membered rings have also been utilized for the stereoselective introduction of halogen atoms.F ukuyama and co-workers installed the chloride-bearing stereocenter of (À)-hapalindole G( 76)v ia opening of activated cyclopropane intermediate 74,w hich was prepared from diazomalonate 73 through copper(II) bis(salicylidene-tert-butylamine)-catalyzed intramolecular cyclopropanation (Scheme 12). [34] Upon heating in the presence of lithium chloride and camphorsulfonic acid, 74 underwent chlorinative ring opening followed by decarboxylation to give the hindered, neo-pentylic chloride 75 in as iteselective and stereospecific manner.…”

Stereoselektive Halogenierungen in der Naturstoffsynthese

“…Diese Reaktivität wurde auch von Vanderwal und Mitarbeitern anhand des Epoxids 70 auf dem Wege zu Danicalipin A beobachtet ( 7 , Abbildung ); die unerwünschte Reaktivität wurde durch die Verwendung eines Überschusses an löslichem Chlorid und einen Wechsel der Lewis‐Säure unterbunden . Carreira und Mitarbeiter führten vor kurzem eine sorgfältige mechanistische Untersuchung durch, die ein wahrscheinliches viergliedriges cyclisches Chloronium‐Intermediat ( 67 ) anstelle eines fünfgliedrigen Ringisomers implizierte …”

[1,3]‐Sigmatropic Shift of an Allylic Chloride

“…[1 -3] Numerous syntheses have showcased diverse strategies, which include unanticipated anchimeric assistance by chlorides in openings of allylic epoxides. [4][5][6][7][8][9][10][11][12][13] Yet, despite the extensive work that has been documented, this natural product class harbors additional surprises in store. Herein we report one such discovery, i. e. a [1,3]-sigmatropic shift of an allylic chloride.…”