Regio‐ and Stereochemical Studies on the Nitroso‐Diels–Alder Reaction with 1,2‐Disubstituted Dienes

Abstract

The regioselectivity of the nitroso-Diels-Alder reaction between unsymmetrical acyclic dienes and Boc-nitroso (Boc=tert-butoxycarbonyl) reagent or the Wightman chiral chloronitroso reagents has been studied. With the Boc-nitroso reagent, the selectivity is a consequence of steric effects at the C1-position in the diene and electronic effects at the C2-position in the diene. The combination of an unprotected hydroxyethyl side chain at C1 and an electron-withdrawing group at C2 allows complete regioselectivity in favour of the proximal isomer. The same isomer was obtained exclusively with the chiral nitroso reagent with high enantioselectivities. A model based on steric effects is proposed.

Stereo- and regioselectivity of the hetero-Diels–Alder reaction of nitroso derivatives with conjugated dienes

“…This general rationale for the regioselectivity of the nitroso hetero-Diels–Alder reactions proposed by Houk [79–80] was clearly summarized by the Kouklovsky group [89] (Table 1). The regioselectivity depends on the nature of the nitroso derivative and on the nature and position of the substituents on the diene.…”

“…Recently, the Kouklovsky group reported a highly regioselective nitroso hetero-Diels–Alder cycloaddition with 1,2-disubstituted dienes, leading to the selective formation of the proximal isomer [89]. First, they studied the reaction of Boc-nitroso (Boc = tert -butoxycarbonyl) reagent 54 with different dienes 55 (Scheme 14).…”

Regioisomeric and Substituent Effects upon the Outcome of the Reaction of 1-Borodienes with Nitrosoarene Compounds

“…More recently, Kouklovsky et al examined 1,2-disubstituted dienes and their reaction with Boc-nitroso compounds to derive nitroso Diels-Alder cycloadducts with high regioselectivity. 7 To predominantly obtain the distal isomer, it is necessary for the diene to bear a bulky substituent at C 1 and an electron donating group at the C 2 position. For the proximal isomer, a non-bulky substituent at C 1 and an electron-withdrawing group at C 2 are required.…”

Catalytic Asymmetric Aza‐Diels‐Alder Reaction: Pivotal Milestones and Recent Applications to Synthesis of Nitrogen‐Containing Heterocycles

“…This assumption is in agreement with reversed regioselectivity of the corresponding catalyst‐free reaction between compounds 111 and 92 b which formed regioisomeric product 113 exclusively at a significantly reduced rate. DFT calculations testify to the asynchronous concerted mechanism of the catalytic cycloaddition reaction (for discussion on regio‐ and diastereoselectivity of nitroso‐DAR refer to [148] ), for similar Brønsted acid‐catalyzed aza‐DAR of NH ‐amidodienes 92 with 2‐azopyridinecarboxylates 93 refer to Scheme 35).…”