Hetero-2-Cyclohexenones

A simple, commercially available chiral alcohol, a,a,a a -tetraaryl-l,3-dioxo-lane-4,5-dimethanol (TADDOL, 7a), catalyzes the hetero- and carbo-Diels-Alder reactions of aminosiloxydienes with aldehydes and a-substituted acroleins to afford the dihydropyrones and cyclohexenones, respectively, in good yields and high enan-tioselectivities. More recently, it was reported that axially chiral biaryl diols 7b and 7c were more highly effective catalysts for enantioselective hetero-Diels-Alder reactions (Scheme 12.5). ... 

The groups of Rueping [25] and Gong [26] have developed the aza-hetero-Diels-Alder reaction of aryl imines and cyclohexenone to give isoquinuclidines in good endojexo selectivities and high yields and ee s by 1 and la, respectively (Scheme 5.13). In the presence of acid, cyclohexenone enolizes to afford the dienol which subsequently undergoes a Mannich reaction with the protonated aldimine followed by intramolecular aza-Michael addition to produce the formal Diels-Alder adducts. 

This principle also allows generation of other very useful 1-hetero-substituted 1-lithio cyclopropanes, e.g. methoxy derivatives which, after treatment with carbonyl compounds and acid, afford 2-vinylcyclobutanones in excellent yields (equation 113). The latter have been expanded to cyclopentenones and cyclohexenones by various methods On the other hand, trimethylsilylcyclopropanes undergo a Peterson-type... 

Numerous investigations of highly enantioselective reactions catalyzed by chiral phosphoric acids (86) continue to be reported. The potential of this type of Bronsted acid in asymmetric catalysis has been demonstrated. The first asymmetric direct hetero Diels-Alder reaction catalyzed by a chiral Bronsted acid has been described. Thus chiral phosphoric acid (86) exhibited superior enantioselectivity, affording fairly good yields and enantioselectivities for reactions of aromatic aldimines with cyclohexenone (Scheme 21). ... 

Kharasch and Tawney (1941) reported that copper salts catalyze 1,4-addi-tion of Grignard reagents to a,jS-unsaturated ketones. Gilman et al. (1952) first discovered that phenylcopper reacts with benzalacetophenone in a 1,4-addition. Subsequently House and associates (1966) have revealed the scope of the conjugate addition of cuprate complexes. Now alkyl, vinyl, and aryl groups can be introduced specifically at the p position of a,jS-unsaturated carbonyl compounds. Transfer of an allyl group from lithium diallylcuprate to 2-cyclohexenone is also known (House and Fischer, 1969). However, ethynyl, cyano, and hetero groups attached to the copper atom are difficult to transfer to electron-poor olefins. 

A chiral bis-sulfonamide catalyst (35) was developed by Tonoi and Mikami and glyoxylates underwent hetero Diels-Alder reaction of Danishefsky s diene to give cyclohexenone derivatives with high ees (Scheme 2.78) [146]. 

---