Wittig olefmation

The lithium etiolate of acetaldehyde DMH has recently been utilized in the opening reaction of the ot-epoxide obtained by DM DO oxidation ofenol ether 142, to provide hemiacetal 143 after mild oxidative acid hydrolysis. The protected carbonyl functionality was subsequently used for the introduction of the trans enyne chain through a Wittig olefmation reaction to provide alcohol 144, which was then transformed into (+)-laurenyne (Scheme 8.37) [71]. 

A one-pot procedure from aldehydes, through Wittig olefmation and a subsequent epoxidation, was also reported. Aldehydes could be converted into a,P,y,8-unsaturated N-acyl pyrroles, which were epoxidized in the same pot to give N-acyl pyrrole-substituted vinylepoxides [32]. 

Several other anionic/pericyclic domino processes use a Horner-Wadsworth-Emmons (HWE) or a Wittig olefmation as the first step. 

In a similar way, carbocycles having a quaternary center could be obtained from acyclic unsaturated 1,3-dicarbonyl compounds [206]. Other combinations are the domino hydroformylation/Wittig olefmation/hydrogenation described by Breit and coworkers [207]. The same group also developed the useful domino hydroformyla-tion/Knoevenagel/hydrogenation/decarboxylation process (Scheme 6/2.14) [208] a typical example is the reaction of 6/2-66 in the presence of a monoester of malonic acid to give 6/2-67 in 41 % yield in a syn anti-ratio of 96 4. Compounds 6/2-68 and 6/2-69 can be assumed as intermediates. 

Besides nucleophilic attack, cyclative cleavage can be eaffected for example by Stille reactions [120], Wittig olefmation reactions [177], Wittig-Horner [178, 179] or metathesis reactions [180-183]. For more details of C-C-bond formation, see Section 3.3.2. 

In accordance with the following scheme the hydroxyaldehyde A was submitted to a Wittig olefmation followed by the mesylation of the hydroxyl group to give the a,)3-unsat-urated compound B which was in turn converted into the telluride C by treatment with the appropriate aryltellurolate. Irradiation of C in the presence of iV-acetoxy-2-thiopyridone gave rise to the cyclic compound D. 

Barbas developed this procedure further by introducing an asymmetric three-component Michael reaction that should be applicable to many other conjugate addition reactions. He used a Wittig olefmation to prepare, in situ, an a,P-unsatu-rated ketone that subsequently underwent a conjugate addition with malonates (Scheme 21) [94]. The rate of the conjugate addition process was observed to be considerably faster than the analogous reaction reported by Jprgensen which was attributed to the presence of triphenylphosphine oxide within the reaction mixture. 

Step 1 Wittig olefmation gives the ( )-alkene as the major product (93 7). Step 5 Corey-Fuchs alkynylation. 

At about the same time, a synthesis of leukotriene-A, also termed SRS-A ( slow reacting substance of anaphylaxis ), which made use of the Wittig olefmation was described77). The ylide of 100 is reacted with ethyl 5-formyl-2,4-pentadienoate 101 to give the ( , , Z, Z)- tetraenoic ester 102. Reduction and mesylation of 102, subsequent conversion into the sulfonium salt, and treatment of the latter with a base yields a sulfonium ylide which is reacted with methyl 4-formylbutanoate 69 to the epoxy-tetraenoic ester 103. After separation of the cis-epoxide by HPLC, 103 was treated with the S-trimethylsilyl derivative of glutathione dimethyl ester N-trifluoroacet-amide. The diastereomeric products thus obtained were separated by means of HPLC and hydrolyzed to 104 77) (Scheme 18). 

A group of scientists of the Agricultural Research Service of the USDA in Beltsville reported two syntheses of JH1 170, the second of which (Scheme 33) included a Wittig olefmation. 4-Methylhex-(J5)-3-enyl bromide 187, obtained from 186 via Julia synthesis, was reacted with propylidenephosphorane 188 to yield 189143). Carbonyl olefmation of 189 with aldehyde 190 gave the 2,6,10-alkatrienoic ester 191 which represents a precursor of JH11441 (Scheme 33). 

Trans P-sinensal 441 is obtained from the aldehyde 438 prepared by selective ozonolysis of trans-famesene 437. Wittig olefmation of 438 with 1-formylethylidene-phosphorane 440 gives trans P-sinensal 441. Reaction of 438 with 1-ethoxycarbonyl-ethylidene-triphenylphosphorane 439 yields the ethyl ester 442, from which 441 can also be obtained 237 (Scheme 77). Furthermore, a working group of the BASF synthesized a-sinensal 443 and p-sinensal 441 using Wittig reactions 238). 

The reaction of the C20 ylide (45 a) with the unsymmetrical C10 dialdehyde, 2,6-dimethyl-2,4,6-octatriene-1,8-dial (49, R = H), shows a remarkable regioselectivity. Only one of the two aldehyde groups participates in a Wittig olefmation, leading uniformly to p-apo-8 -carotenal (48) 4 ). The Wittig reaction between the C20 ylide (45a) and ethyl-2,6-dimethyl-8-al-octatrienoate (49, R = OQHj) correspondingly yields an ethyl-p-apo-8 -carotenate (48, R = OC2H5)s8). 

The Wittig olefmation of 238 with formaldehyde afforded unsubstituted 2-methylidene benzo-l,3-dithiole 239 (Equation 17) <2003TL6845>. 

Other examples of the Wittig olefmation between TTF derivatives bearing one or two aldehyde groups and phosphorus reagents incorporating the l,3-dithiol-2-ylidene moiety have also been described <1998T4655, 2000CEJ1199>. 

The (Z)-stereoselectivity of salt-free Wittig olefmations leading to the thermodynamically less stable cA-alkenes has long been the subject of intense investigations. At one time, the olefmation was thought to proceed via an ionic stepwise process involving a zwitterionic betaine and a 1,2-oxaphosphetane intermediate. However, NMR spectroscopy studies revealed the oxaphosphetane as the only observed intermediate. ... 

Maryanoff BE, Reitz AB. The Wittig olefmation reaction and modifications involving phosphoryl-stabilized carbanions. Stereochemistry, mechanism, and selected synthetic aspects. Chem Rev 1989 89 863-927. 

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