Intramolecular nitrile oxide cycloaddition (INOC) reactions on chiral alkenes were studied in order to evaluate the influence of the double bond configuration on the stereochemical outcome of the process. Oximes 11-16 were prepared, starting from aldehydes 1-4, via Wittig reaction, isomerization of the double bond for the E derivatives, Swern oxidation, and reaction with hydroxylamine. Treatment of oximes 11-16 with sodium hypochlorite gave the nitrile oxides, which were trapped in situ by intramolecular cycloaddition to give the corresponding isoxazolines 17-22 as mixtures of diastereoisomers (Table I). From (2)-alkenyl oximes C-4/C-5 syn products and from (E)-alkenyl oximes C-4/C-5 anti products were obtained, while the relative stereochemistry at C-5/C-5‘ of the predominant isomers was found to be anti in all cases. The assignment of relative stereochemistry was based on ‘H and 13C NMR spectroscopic evidence and on chemical correlations. With Houk‘s approach, MM2 calculations were performed to evaluate the relative energies of the transition structures. The CNO-ethylene fragment was frozen in the ab initio HCNO-ethylene transition structure model geometry, and the substituents were fully optimized by MM2. With the (2)-alkenes, the “small” group of the allylic stereocenter prefers the inside position, the “medium” the anti, and the “large” the outside, with respect to the forming C-0 bond, and the factors controlling the stereoselectivity are mainly steric. On the contrary, with the (E)-alkenes the “medium” group will be inside, the “large” anti, and the “small” outside. In the case of allyl ethers this model is mainly ruled by electronic factors. Quite good stereoselectivities were achieved in the INOC reactions using the allyl ethers derived from glyceraldehyde. A rationale for this result has been proposed.

STEREOSELECTIVITY OF INTRAMOLECULAR NITRILE OXIDE CYCLOADDITIONS TO Z-CHIRAL ALKENE AND E-CHIRAL ALKENES / R. ANNUNZIATA, M. CINQUINI, F. COZZI, C.M.A. GENNARI, L.M. RAIMONDI. - In: JOURNAL OF ORGANIC CHEMISTRY. - ISSN 0022-3263. - 52:21(1987), pp. 4674-4681.

STEREOSELECTIVITY OF INTRAMOLECULAR NITRILE OXIDE CYCLOADDITIONS TO Z-CHIRAL ALKENE AND E-CHIRAL ALKENES

R. ANNUNZIATA
Primo
;
M. CINQUINI
Secondo
;
F. COZZI;C.M.A. GENNARI
Penultimo
;
L.M. RAIMONDI
Ultimo
1987

Abstract

Intramolecular nitrile oxide cycloaddition (INOC) reactions on chiral alkenes were studied in order to evaluate the influence of the double bond configuration on the stereochemical outcome of the process. Oximes 11-16 were prepared, starting from aldehydes 1-4, via Wittig reaction, isomerization of the double bond for the E derivatives, Swern oxidation, and reaction with hydroxylamine. Treatment of oximes 11-16 with sodium hypochlorite gave the nitrile oxides, which were trapped in situ by intramolecular cycloaddition to give the corresponding isoxazolines 17-22 as mixtures of diastereoisomers (Table I). From (2)-alkenyl oximes C-4/C-5 syn products and from (E)-alkenyl oximes C-4/C-5 anti products were obtained, while the relative stereochemistry at C-5/C-5‘ of the predominant isomers was found to be anti in all cases. The assignment of relative stereochemistry was based on ‘H and 13C NMR spectroscopic evidence and on chemical correlations. With Houk‘s approach, MM2 calculations were performed to evaluate the relative energies of the transition structures. The CNO-ethylene fragment was frozen in the ab initio HCNO-ethylene transition structure model geometry, and the substituents were fully optimized by MM2. With the (2)-alkenes, the “small” group of the allylic stereocenter prefers the inside position, the “medium” the anti, and the “large” the outside, with respect to the forming C-0 bond, and the factors controlling the stereoselectivity are mainly steric. On the contrary, with the (E)-alkenes the “medium” group will be inside, the “large” anti, and the “small” outside. In the case of allyl ethers this model is mainly ruled by electronic factors. Quite good stereoselectivities were achieved in the INOC reactions using the allyl ethers derived from glyceraldehyde. A rationale for this result has been proposed.
Settore CHIM/06 - Chimica Organica
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/177017
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