Still—Wittig reaction

Axial ViS. equatorial selectivities of Wittig rearrangements were studied with the f-butylcyclohexane derivatives (89 equation 22) (Table 8). The lithio dianion of acid (89a) prefers equatorial attack. The Bu 02C (89b) and MesSiCsC substituted ethers (89c) undergo nonstereoselective rearrangements. The Still-Wittig reaction of (89d) is the only one among all known 2,3-sigmatropic shifts on this skeleton that prefers axial attack (67 33). 

Chirality transfer through a Still-Wittig reaction provided the C-glycoside (113) from the enol ether (equation 29). The low yield (25%) was mainly due to protonation of the intervening oxyanion to the methyl ether (114) prior to rearrangement. Presumably, this side reaction could have been suppressed with HMPA as cosolvent. ... 

The Wittig reaction is one that IS still undergoing mech anistic investigation An other possibility is that the oxaphosphetane intermedi ate IS formed by a two step process rather than the one step process shown in Figure 17 13... 

Professor Stewart Trippett is an initiator and has led the development of modern organophosphorus chemistry. He is also a founder and the original Senior Reporter of this Report and we were all concerned to hear of his recent illness. All his friends and colleagues wish him well. It is appropriate and significant that the areas where he has contributed so much, those of the Wittig reaction and hypervalent intermediates, are still among the most actively investigated topics. 

The notable increases in theoretical studies of ylides and their reactions reflects similar developments throughout organic chemistry. The renewed interest in the mechanism of the Wittig reaction have continued, but in spite of several years of considerable effort from a number of respected research groups a fully satisfactory explanation is still some way off. 

The fluorophenol could be converted into 56 in four good steps but the insertion of the vinyl group to give 57 by formylation and a Wittig reaction went in only 18% and the cyclo-propanation with a diazoester and Cu(I) (chapter 30) gave poor selectivity in favour of the cis isomer of 57. Worse still, it was necessary to protect the phenol as a methyl ether and the removal of the methyl group, the last step, went in only 52% yield, wasting nearly half of all the material. 

The reactivity of early transition metal silylenoid complexes is still emerging. An example of the chemistry that these complexes can participate in is the sila-Wittig reaction [equation (7.4)].53 In this transformation, a metathesis occurred between the chromium silylenoid 24 and the dimethyl carbonate to afford a new Schrock carbene, 25, and the trimerized product 26. This methodology allowed access a new carbene complex that eluded previous synthetic efforts. 

In the first report on this famous reaction, Wittig expressed a clear preference for the cyclic phosphorane intermediate 22 such as had already been formulated by Staudinger and Meyer in their earlier work. This view became generally accepted onlv many years later35). In this respect, the Wittig reaction did indeed still reflect some prominent features of the underlying research program on penta-coordinated molecules, from which it now evolved rapidly to a very active life of its own 36). 

After it had been proved that the Wittig reaction was suitable, in principle, for polyene syntheses, the linking of a C5 building block with a C15 ylide (6) was chosen for the synthesis of vitamin A acetate (9). Suitable C5 building blocks, such as, for example, P-formylcrotyl acetate (8), were, of course, still unknown at that time. 

Such substitutions using lithium amides, secondary and in some cases tertiary amines as nucleophiles, have been introduced in early sixties as the first expedient method for this unique class of compounds. It is relevant that / ,/ -difluoro- and chlorofluorole-fins readily available through modified Wittig reaction from aldehydes constitute also good ynamine precursors. In the past decade, however, the more versatile lithium aminoacetylide method has gained more prominence. Substitution reactions are still used, among others, for phenyl, tert.-butyl, cinnamyl and cyclopropyl ynamines. 

This new Zh/CHjBrj/TiCl procedure4 provides a mild, non-basic method for the methylenation of ketones (a competitive pinacol dimerization occurs with aldehydes but good yields of the olefin can still be achieved) and offers an important alternative to the standard Wittig reaction. These characteristics are derived from two important observations ... 

Thefcphosphine oxide can be reduced back to the phosphine (for example, with Cl- SiH) while still bound to the polymer and the polymer-bound reagent can be used again. Separation of Ph3P=0 from alkene products after a Wittig reaction can be quite a nuisance so the ease of work-up alone makes this an attractive procedure. 

Two different strategies for the incorporation of the thiazole moiety were used so far either Stille coupling reactions of 4-stannylthiazoles by one group [18, 19] or Wittig-type ole-fination reactions by all others. The latter approach requires either 2-methyl-thiazole-4-carbaldehyde (4, Scheme 1) available from the corresponding ester by reduction [13, 20, 29, 30] or suitable 4-phosphorusmethyl derivatives (3a-d. Schemes 1 and 4) for the more common inverse approach. 

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