Consecutive stereocenters

It becomes intriguing to inquire what leads to the observed contrasteric reactivity. Intensive studies to disclose the origin of Tt-facial selectivity examined various dienes having unsymmetrical 7t-plane, since their reactions potentially generate five or more consecutive stereocenters with one operation. In this chapter, we review the theories to disclose the origin of 7t-facial selectivity in Diels-Alder reactions of the substrates having unsymmetrical 7t-planes. Recent works are discussed. 

In the case of 2,5-cyclohexadienone 70, with a methoxy and a methyl substituent (Scheme 7.19), the syn monoadduct 71 gave 3,4,4,5-tetrasubstituted cyclohexanones, with three consecutive stereocenters. On employing the R, S, S)-ligand 18 in the second addition step, cis-72 (98% de) was found, whereas with (S, R,R)-18 in the second step trans-73 (98% de) was obtained [73]. 

The Fischer projections show that isotactic placement corresponds to meso or m-place-ment for a pair of consecutive stereocenters. Syndiotactic placement corresponds to racemo (for racemic) or r-placement for a pair of consecutive stereocenters. The configurational... 

Although trans-disubstituted olefins are readily prepared by the partial reduction of acetylenes with sodium in liquid ammonia M>, this novel olefin synthesis via hydroboration has a unique advantage over the conventional method in which four consecutive stereocenters can be created in a predictable manner as shown by the following example (Eq. 71)U8). 

Stevastelins are depsipeptides exhibiting immunosuppressant activity. The first total synthesis of stevastelin B was described by Y. Yamamoto and co-workers. To construct four consecutive stereocenters, the Evans aldol reaction and the Roush asymmetric allylation were utilized. In the allylation step, the authors used (S,S)-diisopropyltartrate-derived ( )-crotyl boronate. The anti homoallylic alcohol product formed as the only diastereomer. 

Addition of lithium enolate (56) to trifluorocrotonate (55) proceeded smoothly in almost quantitative yields with excellent stereoselectivity. The intramolecular chelation in 57 retards the retro-aldol reaction. On the other hand, nonfluorinated crotonate (59) provided 60 in a poor yield because of the faster retro-aldol reaction [26]. The stereochemistry of the chelated intermediate (57) was proven by trapping 57 as its ketenesilylacetal (61). Pd-catalyzed Ireland-Claisen rearrangement of 61 proceeded stereospecifically to give a single stereoisomer (62), suggesting a rigid control of the three consecutive stereocenters (Scheme 3.12) [27]. 

Manzamine B (2) (Fig. 7) was isolated by Higa and coworkers from the Okinawan marine sponge Haliclona sp. in 1987 [103] and was thought to be a bio-genetic precursor of manzamine A (Scheme 5). Its structure is characterized by an 11-membered imsaturated azacycle and six consecutive stereocenters in ring B. Due to these difficulties, no synthetic approach has been reported for manzamine B until now. 

Albertshofer, K. Tan, B., Barbas III, C. F. (2012). Assembly of spirooxindole derivatives containing four consecutive stereocenters via organocatalytic Michael-Henry cascade reactions. Organic Letters, 14,1834-1837. 

An organocatalytic triple cascade reaction, followed by an intramolecular sulfa-Michael addition to produce bicyclic rings with six consecutive stereocenters, was also realized [46]. 

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