Stereoselective Synthesis of Conjugated Fluoro Enynes

Abstract

Metalation-electrophilic fluorination of TMS- and TIPS-protected 1,3-benzothiazol-2-yl (BT) propargyl sulfones gave corresponding BT fluoropropargyl sulfones, Julia-Kocienski reagents for the synthesis of fluoro enynes. Both reagents reacted with aldehydes under mild DBU, or LHMDS-mediated conditions, giving high yields of conjugated fluoro enynes with E- stereoselectivity. In comparison to DBU-mediated reactions, stereoselectivity was higher in low-temperature LHMDS-mediated reactions. Two ketones were shown to react as well, using LHMDS as base. In situ removal of the TMS group gave terminal conjugated 2-fluoro 1,3-enynes. Synthetic utility of the fluoro enynes was demonstrated by conversion to internal alkynes and to stereoisomeric fluoro dienes via Sonogashira and Heck couplings.

5-Alkylresorcinol Derivatives from the Bryozoan Schizomavella mamillata: Isolation, Synthesis, and Antioxidant Activity

“…Under these conditions an inseparable mixture (1:4) of the E -alkene 12 and its Z isomer 12′ was obtained. Although a better E -selectivity was expected for this reaction [ 38 ] our results are in line with the data recently reported for Julia reactions using aromatic ketones [ 39 ]. Alternatively, the formation of the double bond at C5′,C6′ was accomplished by a Wittig reaction that yielded compound 12′ as the only isomer ( Scheme 3 ).…”

Synthesis of Monofluoroalkenes: A Leap Forward

“…in which the E-alkene is formed preferentially (Scheme 48). 64 During the reaction, partial deprotection of the TMS group was observed. Thus, treatment with tetrabutylammonium fluoride was performed after the total consumption of the aldehyde to give the deprotected terminal alkyne.…”

“…Part of their worked concerned the optimization of the stereoselective synthesis of conjugated fluorinated enynes using TMS-protected fluoropropargyl benzothiazol-2-yl sulfones. 64 As partial loss of the TMS group occurred under the reaction conditions, subsequent treatment with a fluoride source was used to complete its removal. High yields were obtained from two ketones when using LiHMDS as the base, and perfect E selectivity was observed in one case where the ketone had two different substituents (Scheme 204).…”

Synthesis of Regiospecifically Fluorinated Conjugated Dienamides

“…Fluorine is an attractive substituent in pharmaceuticals, in agrochemicals, and in materials chemistry [ 14 , 15 , 16 ] due to its effect on physical, chemical, and biological properties of compounds [ 17 , 18 , 19 ]. Julia-Kocienski olefinations [ 20 , 21 , 22 , 23 ] have been explored for the synthesis of various functionalized fluoroolefins [ 24 , 25 , 26 ] by us [ 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] and by others [ 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 ]. In the course of our recent work, we became interested in the use of bifunctional Julia-Kocienski reagents, or their precursors, for novel modular assembly of vinyl [ 33 , 47 ] and fluorovinyl [ 33 ] compounds.…”