Allyl Wittig olefination

Retrosynthetic considerations reveal an approach (Scheme 1.2.6) in the first step based on disconnections of the C -Cy and C12-C13 double bonds. Those can be built up using highly B-selective Wittig olefinations between allyltributylphos-phorous ylides derived from the corresponding allylic bromides 29 and 31 [31]. The aldehyde 30 is accessible from the keto ester 33, which can be prepared in high enantiomeric purity by a biocatalytic enantioselective reduction of a... 

Octoses.1 A new route to octoses involves catalytic osmylation (7, 256-257) of allylic alcohols derived from a hexose by Wittig olefination to introduce two... 

Stereoselective allylic alkylations have been carried out with the aid of palladium catalysts. The 17-(Z)-ethylidene groups of steroids (obtained from the ketones by Wittig olefination) form n-allyl palladium complexes in the presence of copper(n) salts (B.M. Trost, 1974, 1976). Their alkylation with dimethyl malonate anions in the presence of 1,2-ethane-diylbis[diphenylphosphine] (— diphos) gives a reaction exclusively at the side chain and only the (20S) products. If one starts with the endocyclic 16,17 double bond and replaces an (S)-20-acetoxy group by using tetrakis(triphenylphospbine)palladium,the substitution occurs with complete retention of configuration, resulting from two complete inversions (B.M. Trost, 1976). 

A Michael-type addition of secondary amines or thiols to 3-methylene-2-oxetanones (33) and subsequent pyrolysis of the adduct (34, X = NR22 or SR2) to yield allylic amines (35, X = NR22) or sulphides (35, X = SR2) has been proposed as a useful alternative to the Wittig olefination procedure (95JOC578). 

After reduction of the enal with diisobutylaluminium hydride, the Wittig olefination of D-glycer-aldehyde acetonide (7 )-24 with Ph3P=CHCHO gives the ( )-allylic alcohol 129. The Katsuki-Sharpless enantioselective epoxidation [89] applied to 129 allows the preparation of D-arabinitol (= D-lyxitol) and ribitol, a meso alditol (Scheme 13.47). Similarly, Wittig olefination of R)-2A with Ph3P=CHCH(OEt)2, followed by acidic hydrolysis of the diethyl acetal and subsequent reduction of the enal with diisobutylaluminium hydride, provides the (Z)-allylic alcohol 130. Diastereoselective epoxidation and hydrolysis leads to D-arabinitol or xylitol, another meso alditol [90a]. 

A carbonyl transposition can be effected via the addition of a vinyl or an alkyl Grignard reagent to an a, 3-unsaturated ketone. Acid-catalyzed rearrangement of the resultant allylic alcohol during oxidation with PCC affords the transposed a,(3-unsaturated carbonyl substrate. This reaction represents a useful alternative when Wittig olefination of the ketone is problematic. 

Kulkarni, M. G., Pendharkar, D. S., Rasne, R. M. Wittig olefination an efficient route for the preparation of allyl vinyl ethers - precursors for... 

The strategy eluded to in Scheme 7.3.6 is elaborated upon in Scheme 8.10.3 and involves the allyl sugar derivative shown. Conversion of the allyl group to the phosphonium salt is accomplished in eight steps. Wittig olefination with the illustrated protected aldehyde provides the cis olefin which is dihydroxylated under asymmetric conditions and selectively protected as the PMB ether. 

Chiral allylic acetates 426 can be prepared using a similar j5-ketophosphonate (425), also derived from lactic acid. The desired 425 is formed via reaction of lithiated diphenylphos-phonate with 401. Reduction of the ketone gives an intermediate alcohol which, upon treatment with base, forms the ( )-Wittig olefin. Removal of the silyl protecting group followed by acetylation gives the product 426 (> 98% ee) [133]. 

The synthesis of (5 S)-thiolactomycin (792), an enantiomer of an antibacterial agent, makes use of a Wittig olefination early in the sequence as a way of preparing a,jS-unsaturated ester 786 (Scheme 106). The key step in the synthesis is an allyl xanthate-dithiocarbonate rearrangement of 788 to 789. This process occurs upon distillation of 788 at 145 °C (0.4 mm Hg) and gives the desired product 789 in nearly quantitative yield. Chirality transfer is equally efficient, with an enantiomeric excess of at least 98% [222]. 

The first configurationally stable l-oxy-2-alkenyllithium 253 was reported in 1986 by Hoppe and Kramer [Eq. (70)] [8]. It was generated by deprotonation of the enantioenriched allyl carbamate 252, obtained fi om the corresponding alcohol via kinetic resolution through Sharpless epoxidation. More conveniently accessible are the 1-methyl derivatives 254 and analogues either from (R)- or (S)-lactaldehydes via Wittig olefination [154]. Kinetic resolution of rac-254 during deprotonation is also possible [155-157]. 

Hydroxylation of oleic acid, 18 1(9Z), in the allylic positions with selenium dioxide//er/-butylhydroperoxide has been reported (27,28). 9,18- and 10,18-Dihy-droxy-18 0 were prepared by condensation of two a,co-difunctional synthons derived from suitable a,co-alkanediols (29). The synthesis of 7,10-dihydroxy-18 1 (8E) was achieved by Wittig olefination reaction of appropriate synthons (30). 

Wittig olefination was discovered in 1953 during studies on the reactions of pentaphenyl-phosphorane, and was described in the following year as a widely suitable method for olefin synthesis [33]. As early as 1956 a patent application appeared [34], in which the synthesis of retinoic acid esters from p-ionylideneacetaldehyde and (3-alkoxycarbonyl-2-methyl)allyl-triphenylphosphonium bromide was claimed, evidence of the fact that the inventors had rapidly realized the economic potential and industrial practicability of this novel reaction [35,36]. 

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