Efficient synthesis of optically pure
α-(fluoroalkyl)-β-sulfinyl enamines has been achieved by
aza-Wittig reaction of triphenyliminophosphoranes with the corresponding
α-fluorinated-α‘-sulfinyl
ketones. The title compounds 3,4 showed an
overwhelming preference for the Z
stereochemistry
of the enamine form. Their general reactivity has been studied.
The reaction with some
electrophiles (i.e. benzyl chloroformate and benzyl and
allyl bromide) occurs at the nitrogen atom
providing the corresponding N,N-disubstituted
enamines. Nucleophiles add smoothly to C-2:
heteroatom-centered nucleophiles like methanol, ammonia, and thiophenol
afford gem-disubstituted
derivatives under thermodynamic control, while a C-centered
nucleophile like nitromethane adds
in irreversible fashion. The hydride- and deuteride-promoted
reduction of 3,4 to the
N-Cbz-protected
(14) and N-unprotected (15)
α-fluorinated-α‘-sulfinyl amines has been studied. Hydride
addition
was stereoselective, while low stereoselection was obtained with the
other tested nucleophiles.
Desulfurization of the optically pure 1,1,1-trifluoro-3-sulfinyl
amine 15a afforded
(R)-1-(trifluoromethyl)ethylamine 17. The Pummerer rearrangement of
14 occurs in an unusual nonoxidative
way affording the sulfenamide 24, that readily provided
(R)-(2-H)- and -(2-D)-3,3,3-trifluoroalaninol
(19) and (R)-3,3,3-trifluoroalanine
(22).
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.