Wittig olefination, synthetic methods

The reactions described in this chapter include some of the most useful synthetic methods for carbon-carbon bond formation the aldol and Claisen condensations, the Robinson annulation, and the Wittig reaction and related olefination methods. All of these reactions begin by the addition of a carbon nucleophile to a carbonyl group. The product which is isolated depends on the nature of the substituent (X) on the carbon nucleophile, the substituents (A and B) on the carbonyl group, and the ways in which A, B, and X interact to control the reaction pathways available to the addition intermediate. 

Numerous examples of this synthetic sequence, not limited to stabilized phosphoranes, can be found in the literature. The method is supposed to be applicable to all secondary hydroxyl groups of sugar rings. Chain extension at the primary hydroxyl group or at the hemiacetalic carbon using Wittig olefination will be examined later on in this chapter (Section 11.4). 

Synthetic routes to vinylpyrroles and vinyl indoles continue to be of interest because of their potential as Diels-Alder dienes. Work by Settambolo and coworkers demonstrated that 3-acyl-l-p-toluenesulfonylpyrroles can be converted to 3-vinylpyrroles by standard methods such as Wittig olefination or organometallic addition followed by dehydration. <94G173> The tosyl group can be removed by alkaline hydrolysis. 

In 1953 Wittig and Geissler (100) reported that methylene triphenyl-phosphorane reacted with benzophenone to form 1,1-diphenylethene and triphenylphosphine oxide. This experiment marked the birth of the Wittig reaction, a novel method for the conversion of carbonyl groups to olefins, and the entry of ylides into the arsenal of important synthetic tools. Since... 

Because of the preparative potential of this reaction the Wittig carbonyl olefination and its manifold synthetic variants gave rise to a number of new olefin syntheses or improvements of common preparation methods in the following 30 years, and led to investigations of its mechanistic aspects and the stereochemical course. The Wittig reaction nowadays represents one of the key reactions in the preparation of natural compounds and in polyene chemistry3-5), and has found new areas of application in industrial practice 6). 

Although the Schlosser modification of the Wittig reaction provides access to trans-olefins from non-stabilized ylides, the Julia-Lythgoe olefination has proven to be the method of choice for solving this synthetic problem today, a) M. Schlosser, K.-F. Christmann, Justus Liebigs Ann. Chem. 1967, 708, 1-35 b) M. Schlosser, K.-F. Christmann, A, Piskala, Chem. Ber. 1970, 103, 2814-2820. 

The reaction of phosphorus ylides with carbonyl compounds has developed into one of the most important methods for the synthesis of olefins the synthetic potential of the Wittig reaction has been described in a series of review articles [2-7]. Numerous other studies are concerned with the stereochemical course of the Wittig reaction (see Section C) and of the reaction mechanism (see Section D). 

Due to their synthetic utility and pharmaceutical applications, a number of synthetic routes to a,P-unsatuiated nitriles have been developed. Classical methods include dehydration of amides [15] or aldoximes [16], Wittig- [17] and Peterson-type [18, 19] olefination processes, ammoxidation of alkenes [20], and carbocyanation of alkynes [21], These approaches suffer variously from high waste generation, low yields and poor stereoselectivity. As such the transition metal-catalysed cyanation of vinyl halides is an attractive route for the synthesis of alkaiyl nitriles. Whilst several instances of such transformations have been reported in the literature, the area remains underdeveloped, particularly in comparison to analagous cyanations of aryl halides. 

---