Diastereoselectivity Nazarov cyclization

The Ir(lll) complex also funchoned as a catalyst in a tandem Nazarov cyclization-Michael addition. The reaction of monocyclic a-alkylidene-P-keto-y.b-unsaturated ester with nitroalkene gave bicyclic cyclopentenones which possessed an alkyl side chain, with high yield and diastereoselectivity (Scheme 11.36) [47]. 

The Nazarov cyclization has been featured in a variety of synthetic endeavors involving both natural and unnatural products. In the area of polyquinane natural products ( )-hirsutene (88), ( )-mod-hephene (89), ( )-silphinene (90), ( )-A 2)-capnellene (91) and ( )-cedrene, have all been prepared (Scheme 37). The synthesis of (91) is noteworthy in the iterative use of the silicon-directed Nazarov cyclization. TIk divinyl ketones were constructed by the carbonylation-coupling of enol triflates (92) and (95) with the -silylvinylstannane (Scheme 38). llie diquinane (94), obtained from Nazarov cyclization of (93), was transformed into enol triflate (95) which was coupled with the -silylvinylstaimane as before. Silicon-directed Nazarov cyclization of (96) was highly diastereoselective to provide the cis,anti,cis isomer of (16). The synthesis was completed by routine manipulations. 

Allylsilanes are good acceptors of 1,3-dipolar compounds such as nitrones [503] and oxyallyl cations [504]. West et al. have used allylsilanes to trap oxyallyl cations generated during the Nazarov cyclization of l,4-dien-3-ones (Scheme 10.188). The tandem bicyclization provides bicyclo[2.2.1]heptanes with high diastereoselectivity. 

A Lewis acid-catalyzed one-pot sequential transformation of /3-ketoesters, aromatic aldehydes, and NCS was reported. The reaction proceeds by way of JCnoevenagel condensation/Nazarov cyclization/halogenations to give a-chloro-)3-ketoesters in moderate yields with high diastereoselectivities. ... 

Fused indole 232 resulted from the reaction of a donor-acceptor cyclopropane with an indole bearing a Michael acceptor at C2.The products were obtained in good yield with high diastereoselectivity (16 examples, 64-90% yield) (140L3954). Tetracyclic-fused indole 233 was prepared by a [3+3]-cycloaddition of an indol-2-yl carbinol with an azadiene (11 examples, 42-90% yield). This could be followed by an oxidative ring expansion promoted by (bis(trifluoroacetoxy)iodo)benzene to produce a series of indole azepinones (6 examples, 59-71% yield) (14CC11181). Fused indole 234 was synthesized by the first calcium(II)-promoted Nazarov cyclization (87% yield).The substituent a to the ester functionality could vary electron-rich arenes, heteroarenes, and secondary alkyl... 

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). 

Oxidation-initiated Nazarov cyclization of vinyl alkoxyallenes provides a mild method for the diastereoselective formation of C4, C5-disubstituted cyclopentenones (Scheme 6.34) [38],... 

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). 

An interesting catalytic diastereo- and enantioselective tandem transformation via Nazarov cyclization /electrophilic fluorination has been efficiently promoted by a (/ ,/ )-Ph-BOX-Cu(II) complex to afford fluorine-containing 1-indanone derivatives with two new stereocenters with high diastereoselectivity trans/cis up to 49/1) and moderate-to-high enantioselectivities (up to 95.5% ee) (Scheme 44.24). This catalytic enantioselective tandem transformation can be used for synthesis of organofluorine compounds with adjacent carbon- and fluorine-substituted tertiary and quaternary stereocenters. " ... 

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