Selection 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... 

Fig. 11.7. trans-Selective Wittig olefination of aldehydes I—Preparation of a trans-configured a,j8-unsaturated ester (preparation of the starting material Figure 17.24). 

Fig. 11.8. trans-Selective Wittig olefination of aldehydes II—Synthesis of /J-carotene from a dialdehyde. The ylide used here is already known from Figure 11.2. In a way, it is "(semi)stabilized" since it is prepared in situ like a semista-bilized phosphonium ylide, but reacts as trans-selectively as a stabilized ylide. 

The possibility of synthesizing pure (Z)-olefins by means of reactive salt-free ylides predestinates the (Z)-double bond at C-5 in e.g. 106 and 107 to be introduced into the corresponding aldehyde via the Wittig reaction. The ( )-configurated double bond at C-13 (105,106 and 107) with its vicinal hydroxy group was frequently formed by the phosphonate method (cf. Chapter 2). In some cases, however, it could also be obtained by ( )-selective Wittig olefination using resonance-stabilized phosphoranes. 

The synthesis of prostaglandin PGB1 as described by Morin et al. (Eli Lily Research Labs.), starts with 7-(2-methoxyphenyl)heptanoic acid 142 which is converted into 143 through Birch reduction, esterification and acetalization. Ozone cleavage of 143 and cyclization of the resulting dialdehyde affords cyclopentene carbaldehyde 144 which was subjected to ( )-selective Wittig olefination with... 

Fig. 9.12. tram-Selective Wittig olefination of aldehydes II—Synthesis of /3-carotene from a dialdehyde. 

Dipolar aprotic solvent. This cyclic urea can serve as a substitute for the carcinogenic hexamethylphosphoric triamide (HMPT) in reactions of highly nucleophilic and basic reagents. It mimics the effect of HMPT in Wittig olefination und in selective generation of various enolates. It forms homogeneous solutions with I IIF even at -78°. ... 

Maryanoff, B.E. and Reitz, A.B. (1989) The Wittig olefination reaction and modifications involving phosphoryl-stabilized carbanions. Stereochemistry, mechanism, and selected synthetic aspects. Chemical Reviews, 89(4), 863-927. 

The primary alcohol is first oxidized to an aldehyde, which is then the substrate in a Wittig olefination reaction. Here a stabilized ylide is employed and therefore the E double bond is formed exclusively. (For a detailed description of the Wittig reaction see Chapter 13 the selectivity issues are explained in Chapter 9.)... 

The protected methyl glycoside 3 is converted to the corresponding aldehyde by Swern oxidation using oxalyl chloride activated DMSO. Further reaction with triethyl phosphonoacetate and sodium hydride -known as the Horner-Wadsworth-Emmons reaction - provides selectively the trans et /Tun saturated ester 4 in 72 % yield. This valuable alternative to the Wittig olefination protocol uses phosphonate esters as substrates which are readily available from alkyl halides and trialkyl phosphites via the Arbuzov rearrangement.9 co2Et Reaction of the phosphonate with a suitable base gives the... 

Fig. 4.44. syn-Selective eliminations from oxaphosphetanes in Wittig olefinations with unstabilized (upper row gives ris-olefin) and stabilized P-ylides (bottom row gives trans-olefin). 

B. E. Maryanoff, A. B. Reitz, The Wittig Olefination Reaction and Modifications Involving Phospho-rylstabilized Carbanions. Stereochemistry, Mechanism, and Selected Synthetic Aspects, Chem. Rev. 1989, 89, 863-927. 

Fig. 9.8. Optimum cis-selectivities of Wittig olefinations of different aldehydes with nonstabilized ylides under salt-free conditions.

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