Diastereofacial Selectivity in the Cycloaddition of Nitrones to (E)-γ-Oxygenated α,β-Unsaturated Esters

Abstract

The 1,3-dipolar cycloadditions of nitrones 1 and 2 to a series of 1,2-disubstituted electron-deficient olefins bearing an allylic stereocenter, 4-8, are reported. The syn/anti stereochemistry of the major endo adducts may be rationalized through the Houk transition-state model, but the possibility of intramolecular hydrogen bonding must be taken into account. In the case of the minor exo adducts the syn stereochemistry always predominates.

Asymmetric Induction in the Cycloaddition of a Masked p-Benzoquinone to Cyclic Nitrones

“…The cycloaddition of the dioxolane derivative 10b to nitrone 2 was also studied. From this reaction the corresponding cycloadducts 13b and 14b were isolated with poorer yield (63%) and facial selectivity ( anti / syn = 5), in agreement with the lower reactivity and minor sterical demand of nitrone 2 compared to 3 . 9d,e …”

“…At room temperature, the major primary adduct 7a derived from 1a and 3 shows broad absorptions in its 1 H-NMR spectrum, while at 250 K two sets of signals can be observed with a relative intensity of 2:1 corresponding respectively to the trans - and cis -fused invertomers of the azabicyclic system. For the minor cycloadduct 8a , only the trans invertomer is observed at any temperature, as was the case for other closely related cycloadducts with endo stereochemistry 9d. The larger value of the coupling constant J 10a,10b (9.2 vs 6.1 Hz) and the higher chemical shifts presented by C 10 , C 10a , and C 10b for the trans invertomer of the exo adduct 7a in relation to the endo 8a are particularly useful for the stereochemical assignment.…”

“…General. See ref d. The NMR spectra were recorded by Servei de Ressonància Magnètica Nuclear de la Universitat Autònoma de Barcelona.…”

“…Generally, in the cycloaddition of a nitrone to an olefin there are two possible regioisomeric orientations. With 1,2-disubstituted electron poor olefins, a high degree of regioselectivity is usually achieved, in such way that the preferred regioadduct has the oxygen atom of the starting nitrone linked to the electronically more deficient carbon atom of the olefin, although steric factors may also play an equally important role. p -Benzoquinone itself and its symmetric derivatives contain two double bonds that are identical initially, but once a single cycloaddition has taken place, the remaining double bond in the cycloadduct is expected to be more reactive toward the nucleophilic nitrone and therefore chemoselectivity has also to be considered.…”

“…We thought that these compounds could be used as a source of chirality for developing enantioselective nitrone cycloadditions . We therefore decided to investigate the reactivity of p -benzoquinone monoketals toward cyclic nitrones 2 and 3 (Scheme ) as part of a more general study in which other 1,2-disubstituted electron-deficient olefins were also included, 9d-g, and our results are presented in this paper. As will be shown, we have developed a strategy consisting of masking one of each pair of the functional groups of p -benzoquinone, the carbonyl and the double bond, through ketalization followed by transient conjugate addition of thiophenol (Scheme ).…”