Lipase-Catalyzed Domino Kinetic Resolution/Intramolecular Diels-Alder Reaction: One-Pot Synthesis of Optically Active 7-Oxabicyclo[2.2.1]heptenes from Furfuryl Alcohols and β-Substituted Acrylic Acids

The first lipase‐catalyzed domino reaction is described in which the acyl moiety formed during the enzymatic kinetic resolution of furfuryl alcohols (±)‐3 with a 1‐ethoxyvinyl ester 2 was utilized as a part of the constituent structure for the subsequent Diels–Alder reaction. The preparation of ester 2 from carboxylic acid 1 and the subsequent domino reaction were carried out in a one‐pot reaction. Therefore, this procedure provides a convenient preparation of the optically active 7‐oxabicyclo[2.2.1]heptene derivatives 5, which has five chiral, non‐racemic carbon centers, from achiral 1 and racemic 3. The overall efficiency of this process was dependent on the substituent at the C‐3 position of 3, and the use of the 3‐methylfurfuryl derivatives, (±)‐3 b and (±)‐3 f, exclusively produced diastereoselectivity with excellent enantioselectivity to give (2R)‐syn‐5 (91–≥99 % ee) and (S)‐3 (96–≥99 % ee). Similar procedures starting from the 3‐bromofurfuryl alcohols (±)‐3 h–j provided the cycloadducts (2R)‐syn‐5 j–q (93–≥99 % ee), in which the bromo group was utilized for the installation of bulky substituents to the 7‐oxabicycloheptene core. The lipase‐catalyzed domino reaction was developed in which the acyl moiety installed during the enzymatic kinetic resolution of alcohols was utilized as a part of the constituent structure for the subsequent Diels–Alder reaction as depicted. Thereby, the optically active 7‐oxabicyclo[2.2.1]heptene derivatives with five chiral, non‐racemic carbon centers were prepared from racemic furfuryl alcohols and achiral β‐substituted acrylic acids in a one‐pot reaction.