Nazarov cyclization asymmetric reaction

Rueping employed N-triflyl phosphoramide 13d in the Nazarov cydization to afford cis-cyclopentenones with moderate diasterselechvihes in excellent yields and ee s. This represents the first example of an organocatalytic electrocyclizahon reaction [62]. Notably, related asymmetric metal-catalyzed Nazarov cyclizations often provide the trans-product [63]. Later, Rueping applied N-triflyl phosphoramide 13e... 

The Nazarov Cyclization is a rare example of a Lewis acid-catalyzed 4-7t conrotatory electrocyclic reaction. Asymmetric... 

Nazarov, I. N. Torgov, I. B. Terekhova, L. N. Bull. Acad. Sci. (USSR) 1942, 200. I. N. Nazarov (1900-1957), a Soviet Union Scientist, discovered this reaction in 1942. It was said that almost as many young synthetic chemists have been lost in the pursuit of an asymmetric Nazarov cyclization as of the Bayliss-HiUman reaction. 

Almost 10 years after Aggarwal s report, Rawal and coworkers [22] reported the use of chiral chromium-salen complexes to catalyze enantioselective Nazarov cyclizations. While other asymmetric Nazarov reactions had been reported since Aggarwal s publication, the chromium-salen complex 86 was the first to cat-alytically perform the cydization of unactivated divinyl ketones 84 to give cyclic ketones 85 in high diastereoselectivity and enantioselectivity (Scheme 3.19). 

Besides chiral phosphoric acids, also chiral imidodiphos-phoric acids 161 [72], disulfonimides 162 [73], or trifly-limides 163 [74] have emerged as powerful (Brpnsted or Lewis) acid organocatalysts for challenging asymmetric transformations like spiroacetalizations, Mukaiyama aldol reactions, or Nazarov cyclizations (Scheme 6.27). 

Rueping M, leawsuwan W, Antonchick AP, Nachtsheim BJ. Chiral Brpnsted acids in the catalytic asymmetric Nazarov cyclization-the first enantioselective organocatalytic electrocyclic reaction. Angew. Chem. Int. Ed. 2007 46 2097-2100. 

During the last decade, asymmetric Nazarov cyclization was a focus of several research groups.Interestingly, in the course of the electrocylization process, the Nazarov reaction allows for access to a potent chiral enolate. 

Recent applications of the Nazarov reaction, the cyclization of a 3-hydroxyphenyl-penta-l,4-dienyl cation, were reviewed.142 Tandem processes and asymmetric cycliza-tions were a particular focus of attention. Irradiation of (40) in aqueous base results in regioselective and stereoselective formation of (42).143 The allylic cation (41) is proposed as the key intermediate. A computational investigation was performed into the cofacial intermolecular n-n orbital interaction between n-conjugated main chains (C H +2) and allylic cations C3H54".144... 

A similar type of chiraUty transfer was exploited by Tius in the total synthesis of roseophilin (69) (Scheme 3.15) [18]. A key intermediate in the synthetic pathway consisted of a substituted cyclopentanone, constructed via a Nazarov-type cyclization. The asymmetric cyclopentannulation reaction was initiated by generating the cyclopentenyl intermediate in situ using the lithioallene 64 and the amide 65. The chiral substituent on the delocahzed carbocation 66 induced... 

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... 

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