Michael/Wittig reaction

Pseudosugars are yet another class of stable carbohydrate isosteres which are resistant to both chemical and enzymatic hydrolysis at the pseudoanomeric center. Understandably, for the construction of highly functionalized carbocycle the natural choice would be to take advantage of chiral templates to install the chirality endowed on their periphery. A novel [3 + 3]-annulation reaction was planned by a Michael-Wittig reaction between a chiral enal and yUde in which the chirality of the cyclohexane could be drawn from the y-chiral hydroxy group of the enal. 

A stereoselective [3 + 3] annulalion by a Michael-Wittig reaction on the enal 82 derived from 2,3-0-isopropylidene-(/ )-glyceraldehyde and ethyl-3-oxo-(triphenyl phosphoryU-dene) butanoate (69)" in one pot gave the cyclohexenone derivative 83. Enone reduction and stereoselective dihydroxylation led to formation of highly functionalized cyclohexane systans (85a to 85c) (Schone 22.19). 

Scheme 7.35 Cascade Michael/Wittig reaction for the synthesis of cyclohexenones.

Scheme 2.118 Cascade Michael/Michael/Wittig reaction.

Scheme 7.7 Domino Michael-Wittig reaction catalysed by chiral amine catalysis and copper catalysis.

The overall sequence of three steps may be called the Wittig reaction, or only the final step. Phosphonium salts are also prepared by addition of phosphines to Michael alkenes (hke 15-8) and in other ways. The phosphonium salts are most often converted to the ylids by treatment with a strong base such as butyllithium, sodium amide, sodium hydride, or a sodium alkoxide, though weaker bases can be used if... 

Triphenylphosphine gives Michael additions to the activated triple bond of acetylene dicarboxylic esters in presence of acidic compounds HY (Scheme 1). The reactions take place easily at room temperature, even at -10°C [1], through formation of intermediate activated vinylic phosphonium salts, which undergo a subsequent Michael addition of HY. The reactions afford various stabilized ylides which can be isolated in high yields or undergo possibly evolution, for example by intramolecular Wittig reaction [2]. 

Various diphenylphosphine oxide-substituted seven-membered rings 2-200, including also hydroazulenes, were synthesized by a Michael addition of 2-198, obtained from 2-197, and 2-199 followed by a Wittig reaction as developed by Fujimoto and coworkers (Scheme 2.47) [114]. 

Scheme 2.48. Results of the chiral auxiliary supported domino Michael addition/ Wittig reactions.

The following example completes the section of threefold anionic domino processes initiated by a SN-type reaction. As discussed earlier in Section 2.2, the reaction of a five-membered cyclic phosphonium ylide with enones, a, 3-unsaturated esters, and a, 3-unsaturated thioesters provides cycloheptene or hydroazulene derivatives in a domino Michael/intramolecular Wittig reaction. This sequence... 

The retrosynthesis involves the following transformations i) isomerisation of the endocyclic doble bond to the exo position ii) substitution of the terminal methylene group by a more stable carbonyl group (retro-Wittig reaction) iii) nucleophilic retro-Michael addition iv) reductive allylic rearrangement v) dealkylation of tertiary alcohol vi) homolytic cleavage and functionalisation vii) dehydroiodination viii) conversion of ethynyl ketone to carboxylic acid derivative ix) homolytic cleavage and functionalisation x) 3-bromo-debutylation xi) conversion of vinyl trimethylstannane to methyl 2-oxocyclopentanecarboxylate (67). 

Via tandem Michael-type addition followed by an aza-Wittig reaction, 2,3,6,7-tetrahydro- and 2,3,4,5,6,7-hexahydro-lH-l,4-diazepines have... 

Other Degraded Carotenoids. A new synthesis of the fungal sex hormone ( )-(7 , 9 )-trisporic acid B methyl ester (114) utilized as the key step a Michael-aldol sequence on the /3-keto-ester (115) to yield the highly functionalized cyclo-hexenone (116). The latter underwent Wittig reaction with the phosphonium salt (117) to give (114). After basic alumina-catalysed hydrogen exchange in tritiated... 

The tricyclic 76 was obtained from an intramolecular Wittig reaction <98H2287>. The tricyclic 78 was obtained by reaction of 77 with benzyl bromoacetate in the presence of base followed by intramolecular Michael reaction <99T3427>. 

Wittig reaction to give the desired Michael acceptor. A second catalytic conjugate addition using Josiphos or its enantiomer affords with excellent diastereoselectivities the syn- or awf/-l,3-dimethyl derivative. 

One problem that may be encountered with this type of reaction is related to the fact that in solid-phase synthesis reagents generally have to be used in excess. This can occasionally lead to side reactions, ff, for instance, a resin-bound aldehyde is condensed under basic conditions with excess ketone, the resulting enone might undergo Michael addition with an additional equivalent of ketone (Figure 5.10). For some of these enones, the Wittig reaction may represent a superior synthetic method [75]. 

This aldehyde intermediate was then olefinated using the Takai olefination.29 This step was also attempted using the Wittig olefination, but the basic conditions lead to retro-Michael side reactions, hence resulting in low yields. The Takai olefination avoids the use of basic conditions and produced 29 and 30 in good yields. 

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