Asymmetric Hetero Diels-Alder Reaction of Nitroso Compounds Utilizing Tartaric Acid Ester as a Chiral Auxiliary

Abstract

-The regio-and enantioselective hetero Diels-Alder reaction of a nitroso compound with a cyclic dienol, cyclohexa-1,3-dienylmethanol, has been realized utilizing stoichiometric amount of tartaric acid ester as a chiral auxiliary to afford the corresponding dihydro-1,2-oxazine with complete regioselectivity and high enantioselectivity of up to 92% ee.A catalytic version of the asymmetric hetero Diels-Alder reaction of nitroso compounds with the dienol was also achieved to afford the corresponding optically active cycloadducts with up to 83% ee. The addition of MS 4A was crucial to realize reproducible high enantioselectivity.

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

“…Approach based on the activation of a moderately reactive arylnitroso dienophile; coordination of the diene: The Inomata group studied a different system utilizing the coordination of a hydroxylated diene to a tartaric acid ester [150–152]. When they examined the enantioselective hetero-Diels–Alder reaction between nitrosobenzene and ( E )-2,4-pentadien-1-ol ( 225 ) (Scheme 44), they obtained the corresponding dihydro-1,2-oxazine 226 as a mixture of regioisomers.…”

“…In case of the acyclic dienes tested, no regioselectivity was observed, and the products were obtained with poor stereoselectivity (ee 33–55%). However, with cyclic diene 227 , where the diisopropyl tartrate ester was replaced with the bulkier tert -butyl ester 228 and the dienophile 47 was added slowly over three hours, the reaction was completely regioselective, and good stereoselectivity was observed for the hetero-Diels–Alder product 230 (ee values up to 92%) (Scheme 45) [150]. A coordination complex 229 was proposed as source of the regio- and stereoselectivity in which both, the diene and the dienophile, are bound to the tartrate ester.…”