Steric and Conformational Control of the Regioselectivities in the Ene Reaction with Trisubstituted Cycloalkenes:  Comparison of the Enophiles Singlet Oxygen, Triazolinedione, and Nitrosoarene

Abstract

The nitrosoarene ene reaction with the cycloalkenes 1-3 and E-4 proceeds in high twix regioselectivity to afford the hydroxylamine ene products 1a-4a (twix) and 1b-4b (twin, except far E-4 twix). Steric interactions in the enophile attack are responsible for the skew trajectory of the nitrosoarene enophile. For Z-1-methylcyclooctene (Z-4), twin abstraction dominates, caused by conformational constraints (transannular interactions) in the hydrgogen-atom abstraction. The balance between these steric and conformational factors dictates the regioselectivity in the ene reaction

Ene Reactions of Nitrosocarbonyl Intermediates with Trisubstituted Cycloalkenes: “Cis Effect” and Steric and Conformational Factors Drive the Selectivity

“…Comparing these results with those of the three isoelectronic enophiles 1 O 2 , Ar–NO, and TAD (Table 2), some similarities and differences can be noted. 15 As previously shown for the stereoisomeric pentenes 12E and 12Z (Figure 1), the new results confirm the location of the nitrosocarbonyl intermediates between the unselective 1 O 2 and the regiospecific Ar–NO and TAD.…”

“…The results obtained from the oxidative method confirm the remarkable influence of the nitrosocarbonyl substituent on the selectivities in the ene reactions with trisubstituted 1-methylcycloalkenes under the required experimental conditions. Comparing these results with those of the three isoelectronic enophiles 1 O 2 , Ar–NO, and TAD (Table ), some similarities and differences can be noted . As previously shown for the stereoisomeric pentenes 12E and 12Z (Figure ), the new results confirm the location of the nitrosocarbonyl intermediates between the unselective 1 O 2 and the regiospecific Ar–NO and TAD.…”

The Nitroso Ene Reaction: A Regioselective and Stereoselective Allylic Nitrogen Functionalization of Mechanistic Delight and Synthetic Potential

“…In all cases, except for substrate 1f , the hydrogen abstraction at the twix position is the major pathway and no ene product is observed from lone abstraction.

3 Regioselectivity in the ene reaction of ArNO with various trisubstituted alkenes (refs , , ).

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“…Hydrogen abstraction takes place almost exclusively from the twix group, as displayed in the Figures and . The differences in the regioselectivities in Figure have been rationalized in terms of the distinct steric hindrance in the attack of the enophile or on account of conformational effects in the hydrogen abstraction (see section IV.C). , …”

Synthesis and properties of 2-nitrosoadenosine

“…Ene reaction with cyclohexene. Ene reactions with nitroso compounds are limited to reactive derivatives such as nitrosocarbonyl compounds, 21 p-nitronitrosobenzene 22 or pentafluoronitrosobenzene. 23 Also, 4 showed reactivity and with excess of cyclohexadiene the anticipated hydroxylamine 21 was formed in moderate yield, as a 1 : 1 mixture of diastereomers (Scheme 5).…”