Wittig method

This is the only convenient way to make these compounds, since elimination by any other route gives the thermodynamically more stable a,P-unsaturated isomers. This is an illustration of the utility of the Wittig method for the specific location of a double bond. Another illustration is the conversion of cyclohexanones to alkenes containing exocyclic double bonds, for example, ... 

Selected Applications in Synthesis 4.1 Carotenoids, Retenoids and Pheromones.- Classical Wittig methods involving the ylide (146) and the dialdehyde (147) have been used to synthesize (148), a diastereoisomer of decaprenoxanthin.88 The retinonitrile (150) has been prepared as a mixture of four geometric isomers by phosphonate-based olefination of the 1-cis, 9-cis-Ci5-aldehyde (149). It was possible to separate the four isomers of (150) and reduce each of them to the corresponding retinal. 

The above ketone methylenation is applicable to highly hindered ketones, which are usually inert to the Wittig method. For example, a highly hindered tricyclic ketone (norzizanone, 4a) undergoes the methylenylation to give zizaene (4b equation 4). A -Cholesten-3-one (5a) was also converted to the nonconjugated diene 3-methylene-A -cholestene (5b equation 5). ... 

The Wittig methods is, however, problematic on two counts. First of all. 

The Wittig method of olefin synthesis has been extended to include aliphatic aldehydes, for example gaseous formaldehyde and paraformaldehyde, acetaldehyde, propionaldehyde, n-hexaldehyde, acrolein. ... 

Examples of the use of Wittig methods in leukotriene synthesis include the preparation of 13,13-difluoroleukotriene B4 (155)96 and the synthesis of ( + )-LTB4 (159) and homo-LTBa (160) by the reaction of the ylide (156) with the aldehydes (157) and (158), respectively.97 The dihydro-LTBa metabolite (161) and its C-12 epi-analogue have been prepared by a Wittig reaction of the ylide (162) (derived from L-glutamic acid) and the aldehyde... 

The Wittig reaction has been used to construct the side-chain in a synthesis of (-)-sirenin (208), a water mold sperm-attacking hormone.ii The intermediate (206) was generated, without competing formation of the structural isomer (207), by reaction of the ylide (205) with (204) under salt-free conditions in DME. Standard Wittig methods have been used to construct the side-chain in an enantioselective synthesis of (+)-(7 , 9Z)-methyl trisporate (209) and its (9E)-isomer.l 12 The reaction of triphenyl-(vinylimino)phosphorane derivatives (210) with tropones provides a convenient synthesis of 1-aza-azulenes (211) and (212) in either one or two steps (Scheme 28).H The mechanism of the one-step reaction was investigated using deuterium-labelled tropane derivatives. 

These methods of olefin synthesis have now largely been superseded by the Wittig method which gives total control over the position of the double bond and partial control over its geometry. This reaction may be new to you its mechanism follows. 

Coreychose the Wittig method to control the condensation to give (28). The rest of the synthesis went according to plan. 

The Michael reaction can be controlled by making the enamine of the aldehyde and the Wittig method is suitable for the conversion of (16) to (15). In the 2 + 2 cycloaddition, the isopropyl group will prefer to be traits to the new four-membered ring in (12) so the stereochemistry will be correct. 

The condensation is controlled by the Wittig method and hydrogenation adds hydrogen on the opposite side from the large aryl group to give all-equatorial (43). 

Pheromones.—Further use has been made of Bestmann s unitized construction principle to synthesize a variety of 1,5- and 1,6-alkadiene pheromones. Standard Wittig methods have been used to synthesize (3Z,6Z,9Z)-1,3,6,9-nonadecatetraene (142) (Scheme 19) (now identified as a sex pheromone of the winter moth O. brumata), sex attractants (143) of Lasiocampidae species, and the trail pheromone (144) of Pharaoh s ant. A variety of 2,4-dienoic ester insect juvenile hormone analogues (145) with terminal cyclohexene, cyclohexane, or pinene rings have been prepared by phosphonate olefination. The queen... 

As stated in Sect. 1, there are a number of reviews [19-29] and monographs [30-32] on the quinazolines and quinazoline alkaloids. Also the synthesis of heterocyclic natural products by the aza-Wittig method has been reviewed recently by Eguchi [108-110], and Fresneda and Molina have reviewed timely the application of iminophosphorane-based methodologies for the synthesis of natural pro ducts [ 111 ]. In this section, selected topics on synthesis of quinazoline alkaloids will be discussed retrospectively focusing on these synthetic methodologies. 

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