Subject Wittig directed

The intermediacy of the betaines used in the mechanistic discussions of the Wittig reaction has been questioned and Vedejs has proposed an alternative explanation. The Wittig reaction is subject to solvent effects that indicate a nonpolar transition state for stabilized ylids.There appears to be no direct evidence for the presence of betaines, and none have been isolated. Alternatively, Vedejs and Snoble detected oxaphosphetanes as the only observable intermediates in several Wittig reactions of nonstabilized ylids, using 3Ip NMR. In more recent work, Vedejs devised a test for the betaine mechanism based on changes in phosphorus stereochemistry in the proposed intermediates (betaine vs. oxaphosphetane). The results of this test suggested that "the conventional betaine mechanism l can play at most a minor role in the Wittig reaction".Vedejs points out that the "stereochemical test does not necessarily disprove mechanisms via intermediates with lifetimes that are short compared to the time scale of bond rotation. "494... 

The Wittig-Horner olefination of the aldehyde 28 provided alkenes 29 which were subjected to radical cyclization leading to benzofused tricyclic j6-lactams 30, obtained as single diastereomers (Scheme 8) [36]. A convenient, direct regio- and stereoselective route to optically pure unusually fused or bridged tricyclic /3-lactams has been developed by the use of intramolecular nitrone-alkene cycloaddition reactions. For example, the aldehyde 21 can be transformed into nitrone 31 which subsequently was used for a variety... 

There has so far been only limited success in attempts to produce P-C compounds directly from elemental phosphorus, although both white and red forms are subject to attack by a variety of nucleophilic reagents. These and other synthetic methods are discussed below in this chapter. Synthesis of P-C bonds has recently been comprehensively reviewed [21]. The synthesis of P=C and P=C bonds is dealt with in Sections 6.14 and 6.15 (see also Phospha-Wittig reaction (6.445)). Carbophosphenes can be obtained from carbophosphynes and vice versa (6.631,6.631a), although these are not general methods of preparation. 

Alternative routes to pyrimidines, that avoid the later hydrogenation steps, were developed at Hoffmann-La Roche [46]. This alternative synthetic strategy is shown in Fig. 36. An amino-imine can be prepared in the same way, but this time it is not reacted with a substituted phenylmalonate. Instead an alkoxybenzaldehyde is subjected to a Wittig reaction with the phosphorus ylide of chloromethoxymethane to yield l-(4-al-koxyphenyl)-2-methoxyethane. Treatment with triethoxymethane in the presence of a Lewis acid such as boron trifluoride ether-ate gives the tetraethoxy derivative. Hydrolysis produces 2-(4-alkoxyphenyl)-3-me-thoxypropenal, reaction of this material with the imine results in the pyrimidine being formed directly. 

---