Nazarov cyclization reactions chiral catalysts

Rueping and co-workers have reported one of the most impressive examples of a Nazarov cyclization under asynunetric catalysis. They have shown that chiral Bronsted-acid catalysis outperforms the chiral Lewis acid catalysts used to date and have demonstrated the efficient cyclization of a variety of substrates 79 with moderate to excellent diastereoselectivity and good to excellent enantioselectivity. Only low catalyst loadings (2 mol %) are required of chiral acid 81 to catalyze the reaction efficiently. Interestingly, the reaction primarily generates the cw-cyclopentanones 80a, as opposed to the Lewis acid-catalyzed reactions that provide the trans-product (see 73). 

Another way to induce torquoselectivity involves the use of chiral catalysts. In 2003, Aggarwal and Belfield disclosed the first asymmetric Nazarov reaction catalyzed by a chiral LA complex (Scheme 3.16) [19]. It was found that a complex formed between copper bromide and tridentate ligand 71 was capable of controlling the conrotation of the cyclization of precursor 70 in good enantioselectivity and yield. With substrate attached, the resulting complex 73... 

The Nazarov reaction belongs to a type of 4n electrocyclization and can usually be promoted by metal-based catalysts. In 2007, the first enantioselective organo-catalytic Nazarov reaction was reported by Rueping and coworkers [35aj. A chiral N-triflyl-phosphoramide 101 was a better selection for the cyclization of dienone substrates 102, and cyclopentenone products 103 were generated as a diastereo-meric mixture but with excellent enantioselectivity at low catalyst loadings (2 mol%) (Scheme 36.27). 

---