Wittig Reaction catalytic asymmetric

A challenging goal is the development of catalytic asymmetric induction processes. Denmark et al.48 have reported an asymmetric Wittig reaction using... 

The Wittig reaction currently occupies a central position in the arsenal of the synthetic organic chemist due to its versatility and generality. Ongoing advances in understanding its reaction mechanism and the ensuing catalytic, asymmetric and solid phase applications will permit its continued application to new and exciting synthetic problems. 

Starting from (+)-diethyl tartrate (2), bromobutenolide 18 was obtained in nine steps. Three of the four C=C double bonds were built up using a Wittig reaction (11—>12), an Ando- y Q Horner-Wadsworth-Emmons reaction (13— 15) and (3-elimination (16 18). From (-)-actinol (3) stannane 23 and sulfone 24 were synthesized in 9 and 13 steps, respectively. Their common intermediate, alkyne 22, was synthesized using methoxycarbonylation. Sharpless asymmetric epoxidation and Ci-elongation with lithio trimethylsilyldiazomethane. Stannane 23 was obtained upon hydrostannylation and TBS deprotection. Sulfone 24 was obtained after addition to methyl tetrolate, reduction, Mukaiyama redox condensation, acetylation and catalytic oxidation. 

Sharpless also found that this reaction works with only a catalytic amount of titanium-tartrate complex because the reaction products can be displaced from the metal centre by more of the two reagents. The catalytic version of the asymmetric epoxidation is well suited to industrial exploitation, and the American company J. T. Baker has employed it to make synthetic disparlure, the pheromone of the gypsy moth, by oxidation of the epoxy alcohol to an aldehyde with pyridinium dichromate (PDC) (p. 543), Wittig reaction (p. 689), and hydrogenation. 

Recently, asymmetric induction mediated by external chiral ligands that are not covalently bonded to the reagent has attracted much attention, and it is believed that the information obtained from these studies will prove useful in developing a novel system for efficient catalytic asymmetric transformation. In order to explore the possibilities, a variety of reaction systems capable of effective asymmetric induction at a specific site in the course of a reaction have been devised, and several investigations have also been directed towards Wittig-type olefination. An early study using an optically active organic acid with stabilized ylides [22] was unfruitful, as discussed in the introductory section. 

A catalytic triple domino Michael-aldol-oxa-Michael reaction of acetaldehyde with ( -2-(2-nitrovinyl)phenols catalyzed by (R)-2- diphenyl [(trimethylsilyl)oxy] methyl pyrrolidine followed by a sequential one-pot Wittig, Michael/Wittig-Horner reactions with PPh3=CHC02Et was applied to the asymmetric synthesis of polyfunctionalized chromans (14EJO3076). 

The 1,5-anti-aldol reaction was performed with chiral boron enolate of 325 and aldehyde 327, prepared by Evans asymmetric alkylation, cross metathesis, and Wittig homologation (Scheme 72), to afford 324 with a 96 4 diastereoselectivity. Stereoselective reduction of C9-ketone provided the 5y -l,3-diol, which was exposed to catalytic f-BuOK to give 2,6-cis-tetrahyderopyran 333 via an intramolecular Michael reaction. Finally, methyl etherification, deprotection, hydrolysis of ester, and Yamaguchi macrolac-tonization yielded the leucascandrolide macrolide 201 (Scheme 73). 

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