Wittig chemistry

In the BASF synthesis, a Wittig reaction between two moles of phosphonium salt (vitamin A intermediate (24)) and C q dialdehyde (48) is the important synthetic step (9,28,29). Thermal isomerization affords all /ra/ j -P-carotene (Fig. 11). In an alternative preparation by Roche, vitamin A process streams can be used and in this scheme, retinol is carefully oxidized to retinal, and a second portion is converted to the C2Q phosphonium salt (49). These two halves are united using standard Wittig chemistry (8) (Fig. 12). 

The retrosynthetic concept of the Nicolaou group is shown in Scheme 22. The target molecule 36 is disconnected via an IMDA cyclization of the diene quinone precursor 138, which would be generated from the tetraline derivative 139 using Wittig chemistry followed by aromatic oxidation. A Claisen-type rearrangement would provide access to 139 whereby the side chain required for the rearrangement of 140 would be introduced by 0-acylation. The core of 141 would be formed via an intermolecular Diels-Alder reaction between diene 142 andp-benzoquinone 130 [42]. 

Many of the enone substrates used in polyamino acid-catalysed epoxidation reactions can be made via a simple aldol condensation, which leads directly to the desired enone after in situ dehydration. Enones that cannot be synthesised by the above route may often be synthesised using standard Wittig chemistry, (Scheme 6). The above methods of substrate synthesis provide compounds with a variety of groups R and enabling the incorporation of both aliphatic and aromatic moieties into the enone structure. 

The straight chain congeners of GT-2208 and GT-2209 were synthesized from aldehyde 49 which is readily available from urocanic acid. Wittig chemistry provides the cis olefin 50 from 49 (Figure 24). The irons olefin 51 is obtained from Na (lig. NH3) reduction of acetylene 52 (Figure 24). 

A few instances of neutral acyclic A(-acyl imino dienophiles have been reported. Some of these imines can be prepared and isolated, but often they are generated in situ. For example, Wittig chemistry... 

These phosphines are typically used as ligands for catalytic reactions such as hydroformylation, hydrogenation, dimerization, and other metal-catalyzed reactions. Other uses for the phosphorus derivatives are Wittig chemistry (vitamin A and E), phase-transfer catalysis, epoxy curing, extractants, and agricultural and pharmaceutical intermediates. 

The second obvious way of converting the side chain at C-6 into a nucleophilic center is by means of Wittig chemistry. Thus, the phosphonium bromide 229 has been used to prepare both yangonin (19a) (82JHC157) and the methyl ether (262) of tetraacetic acid lactone (74JOC3615) by Wittig reactions. 

A further aldehyde linker has been constructed using Wittig chemistry [82] (Scheme 33). The alkene 71 created by the Wittig reaction was deaved by ozonol-ysis, and subsequent work-up with dimethyl sulfide yielded the aldehyde 72. The feasibility of this principle was demonstrated in the synthesis of a library of peptide aldehydes. 

Leumann reported the syntheses of 5 -C-butylthymidine, 5 -C-butyl-2 -deoxy-5-methylcytidine and 5 -C-isopentyl-2 -deoxy-5-methylcytidine. These analogues were prepared from natural thymidine using Wittig chemistry on thymidin-5 -al, followed by epoxidation of the alkene and reduction to the 5 -alcohol. The 3 -phosphoramidite derivatives (42a,b) and (43a,b) were prepared for their incorporation into oligodeoxynucleotides, so as to investigate the effects of these 5 -modified nucleosides on the stability of the DNA double helix... 

Many methods for the preparation of both the a- and )8-C-glycosides have been developed, and new approaches are still appearing in the literature. This chapter covers the literature from the end of 1994 to early 1999, with other inclusions as deemed appropriate. Following the organization of earlier work [1], we select the mode reactivity of the anomeric center to define the category. The chapter discusses free radical chemistry. Cl anions, Wittig chemistry-cyclization chemistry, transition metal mediated chemistry, sigmatropic chemistry, and approaches based on cationic chemistry. The chapter focuses on the most recent and novel developments in the field, but all the relevant references are included whenever possible. 

With the variety of methods used, in conjunction with Wittig chemistry, for the formation of C-glycosides, it is helpful to compare the results of one method to another. Several reports have accomplished this. As shown in Scheme 7.1.8, Freeman, et al.,8 effected the cyclization of a Wittig-derived hydroxy olefin to the furanosyl C-glycoside shown. The reagents utilized in this report encompass both halogen and metal mediated cyclizations and provided the desired product in yields as high as 65%. 

Alkenes can be considered as a class of protected carbonyl compounds since they can be converted into carbonyls by ozonolysis. Hall [69] demonstrated a practical strategy for solid phase synthesis of peptide aldehydes using an olefinic linker, which was constructed using Wittig chemistry. After normal peptide synthesis using the alkene linker, ozonolysis of the linker and subsequent workup with... 

Similarly, 29 can be formed by the Homer-Wadsworth-Emmons modihcation of the Wittig reaction via the phosphonate 28 rather than the phosphorns ylide 27. In this case, the iodo compound mixture 26 is treated with trimethyl phosphite. Cyclization reqnires the nse of lithinm chloride/Hunig s base, ° and cyclization proceeds smoothly at room temperature in similar yield to the Wittig chemistry. Details of this process with isolation and characterization of the intermediates 26, 27, and 29 can be fonnd in a recently pnblished world patent application." Yields for the conversion of 24 into 27 are -77% overall cyclization yield from 27 to 29 is -85%. 

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