A Highly Stereoselective One-Pot Tandem Consecutive 1,4-Addition-Intramolecular 1,3-Dipolar Cycloaddition Strategy for the Construction of Functionalized Five- and Six-Membered Carbocycles(,)(1).
Nitronates 3, possessing a suitably located olefinic moiety and arising from conjugate addition of Grignard reagent 2 to nitro olefins 1, are trapped as silyl nitronates 8 which undergo a facile intramolecular 1,3-dipolar cycloaddition. The resulting N-(silyloxy)isoxazolidines 9 are readily transformed into isoxazolines 6 and 7 upon treatment with acid, thus completing the entire sequence in one pot. While cycloaddition to the five-membered carbocycles, in general, proceeds smoothly at rt in a stereospecific manner, that to the six-membered ring is sluggish and less selective. The advantages of this strategy over the intramolecular nitrile oxide cycloaddition, namely greater stereoselectivity and adaptability to one-pot conditions, have been demonstrated. Extensive NMR investigations unravelled the stereochemistry unambiguously and underscored the inadequacy of coupling constants alone in determining the stereochemistry in cyclopentane systems. The explanation advanced to account for the selectivities, in terms of subtle differences among the putative transition state geometries, is in qualitative agreement with widely accepted assumptions pertaining to 1,3-dipolar cycloadditions.
Namboothiri
I. N. Narayanan
IN
Department of Chemistry, Bar-Ilan University, Ramat Gan 52900, Israel.
Hassner
Alfred
A
Gottlieb
Hugo E.
HE