Enantioselectivity diene coupling

In addition, Zhou et al have developed diastereo- and enantioselective reductive coupling of 1,3-dienes, such as l,4-diphenylbuta-l,3-diene, with aromatic and heteroaromatic aldehydes by using ZnEt2 as the reducing agent and nickel complexes of chiral spiro phosphoramidites such as 21 (Scheme 4.21). In this case, the three-component reaction provided the... 

Enantioselective catalysts have been developed for cyclization of dienyl aldehydes and coupling of aldehydes with alkynes (Equations (74) and (75)). For reactions with dienes see Refs 433 and 433a, and for reactions with alkynes see Refs 433b I33e. Chiral monodentate phosphines have proved to be effective. 

Cross-Coupling of Halides. 4,4-Dimethyl-1-phenylpenta-1,2-diene has been prepared using a ((-)-(2f ,3f )-DIOP)PdCl2-catalyzed cross-coupling reaction, although low enantioselectivity was observed (eq 5). ... 

The enantioselective total synthesis of (+)-ambruticin was accomplished in the laboratory of E.N. Jacobsen. The Kumada cross-coupling was utilized to convert an ( )-vinyl iodide intermediate to the corresponding conjugate diene in good yield. The stereochemistry of the vinyl iodide was completely preserved. 

Intramolecular cross-coupling of prochiral inflate 61a, which contains a pair of enan-tiotopic alkylboranes and is generated by hydroboration of prochiral diene 60a, was examined with palladium catalysts coordinated with several chiral phosphine ligands (Scheme Highest enantioselectivity in forming cyclopentane derivative (R)-62 of 28% ee was observed with ferrocenylbisphosphine 63. In the cychzation of 60b, which has a quaternary carbon center, the enantioselectivity was a httle higher, PPFA (5) giving 62b of 31% ee. 

In 2005, MacMillan reported an enantioselective organocatalytic intramolecular Diels-Alder reaction (IMDA) of a,p-unsaturated aldehyde and diene, as well as the application in the asymmetric synthesis of solanapyrone D (6), Scheme 3.1 [5]. Later, Danishefsky and Christmann individually reported the total synthesis of UCS1025A (9) by coupling reaction with MacMillan aldehyde (8) [6]. The malim-ide analogue 10 of the telomerase inhibitor UCS1025A (9) was also prepared by Christmann et al. by modified MacMillan s conditions (10 mol% catalyst loading in nitromethane, affording 74% yield and >99% ee after a sequence of recrystallization and oxidation). Scheme 3.2 [7]. 

One of the earliest examples of organocatalytic Diels-Alder reaction applied in total synthesis of natural products is that Kinsman and Kerr [51] reported an enantioselective total synthesis of hapalindole Q (136) in 2003 (Scheme 17.23). The key step of the synthesis is that diene 133 was coupled with enal 132 through the use of imidazolidinone 134 to afford Diels-Alder adduct 135 in 35% yield (85 15 dr (endo. exo), 93% ee). Even though the catalyst loading (40 mol%) is high, imidazolidinone 134 can be recovered in almost quantitative yield. Adduct 135 was subsequently converted into optically active hapalindole Q (136). 

This methodology has been expanded to synthesize allyl silanes from silylated l,3-dienes. Both Z- and -isomers could be obtained by varying the ligand used in the reaction. It should be noted that an increase in yield was observed when PPhs was added to the nickel-NHC system. While no erosion in selectivity was observed, the phosphine is proposed to stabilize the active nickel species [95]. Finally, use of a chiral NHC allowed for an enantioselective coupling of a variety of aldehydes, 1,3-dienes, and silanes [96]. 

Under optimized conditions, this coupling reaction was extended to various 1,3-dienes and aldehydes providing couphng products (Z)-83 in good yields, with high regio-, diastereo- (anti selective), and enantioselectivities (up to 97% ee) (Scheme 5.62). 

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