Olefination Wittig condensation

For the preparation of sphingosine (21), which has a trans-olefinic linkage, Reist and Christie [40] started from the ethoxycarbonyl derivatives (13) and (15) and modified the conditions of the Wittig condensation so that the product (17) was predominantly the trans-olefin. Periodate oxidation and subsequent borohydride reduction of (17) gave (19) and the ethoxycarbonyl group was removed with barium hydroxide to give sphingosine (21). 

The same year, Gerlach described a synthesis of optically active 1 from (/ )- ,3-butanediol (7) (Scheme 1.2). The diastereomeric esters produced from (-) camphorsulfonyl chloride and racemic 1,3-butanediol were fractionally recrystallized and then hydrolized to afford enantiomerically pure 7. Tosylation of the primary alcohol, displacement with sodium iodide, and conversion to the phosphonium salt 8 proceeded in 58% yield. Methyl-8-oxo-octanoate (10), the ozonolysis product of the enol ether of cyclooctanone (9), was subjected to Wittig condensation with the dilithio anion of 8 to give 11 as a mixture of olefin isomers in 32% yield. The ratio, initially 68 32 (E-.Z), was easily enriched further to 83 17 (E Z) by photolysis in the presence of diphenyl disulfide. The synthesis was then completed by hydrolysis of the ester to the seco acid, conversion to the 2-thiopyridyl ester, and silver-mediated ring closure to afford 1 (70%). Gerlach s synthesis, while producing the optically active natural product, still did not address the problem posed by the olefin geometry. 

Wasserman s second synthesis, shown in Scheme 1.11, was similar to a strategy utilized by Gerlach. Anion 39 was alkylated with the acetal of 6-iodohexanal and deprotected to produce aldehyde 42. A Wittig condensation with the dilithio dianion of racemic 8 afforded the known intermediate 40 as an 8 2 mixture of ( )- and (Z)-olefin isomers, respectively. 

The most important coupling reaction for the synthesis of carotenoids is the Wittig reaction or Wittig-carbonyl olefination or Wittig condensation in which a phosphorus ylide 3 reacts with a carbonyl compound 4 to give an olefin 5 and triphenylphosphine oxide (6) Scheme 1). 

Recently, Meier et al. synthesized the most extended OP Vs (81) known to date [104]. Four different synthetic pathways were used for the generation of these OP Vs the final step involves the formation of one or two olefinic double bonds via a Wittig-Horner-type, a Siegrist-type or a McMurry-type condensation. 

A second convergent synthesis of haliclamine A (64) was achieved in a stepwise sequence from cyclopropyl(thiophen-2-yl)methanone (76) (Scheme 7) [37]. The protected thiophene 77 was condensed with formyl-piperidine to give 78, suitable for a Wittig olefination with 79. After desulfurization of the product 80, the deprotected alcohol 82 was subjected to homoallylic rearrangement using MesSiBr in the presence of ZnBr2. The re-... 

After these results had established the feasibility of generating and utilizing a carbohydrate phosphorane, the two systems that had been reported earlier were examined in order to determine if similar conditions would allow them to undergo the Wittig reaction. The ylide derived from phosphonium salt I condensed with both benz-aldehyde and U-chlorobenzaldehyde to produce good yields of olefinic products Villa and Vlllb. The ylide derived from phosphonium salt II also was successfully condensed with benzaldehyde, but the yield of IX was only 30 , presumably because of its extremely poor solubility even in an HMPA-THF solvent mixture. Both of these systems supported the tenet that it was possible to use unstabilized carbohydrate phosphoranes if the conditions are proper and if the g-oxygen is attached to the carbohydrate through another set of bonds. 

The reactions described in this chapter include some of the most useful synthetic methods for carbon-carbon bond formation the aldol and Claisen condensations, the Robinson annulation, and the Wittig reaction and related olefination methods. All of these reactions begin by the addition of a carbon nucleophile to a carbonyl group. The product which is isolated depends on the nature of the substituent (X) on the carbon nucleophile, the substituents (A and B) on the carbonyl group, and the ways in which A, B, and X interact to control the reaction pathways available to the addition intermediate. 

A pentopyranoside-fused butenolide is the key intermediate for the synthesis of the natural micotoxin patulin [226, 227]. Its synthesis involves Wittig olefination of a 3,4-di-O-protected arabinopyran-2-uloside, followed by protecting group removal and dehydration (Scheme 47). In other research, the glucopyranosid-2-uloside 190 was converted into the butenolide derivative 191 by aldol condensation with diethyl malonate and transesterification [228]. The latter was shown to be prone to autoxi-dation, leading to 192. Subsequent Michael addition with hydroxide ion, followed by decarboxylation, furnishes C-branched-chain sugar 193. 

The Wittig reaction efficiently olefinates aldehydes and ketones, but not esters or amides. Several early-transition-metal approaches have been taken to this problem. Recently, Takeshi Takeda of the Tokyo University of Agriculture and Technology reported (Tetrahedron Lett. 44 5571,2003) that the titanocene reagent can effect the condensation of an amide 10 with a thioacetal 11 to give the enamine 12. On hydrolysis, 12 is converted into the ketone 13. When the reaction is intramolecular, reduction proceeds all the way, to give the pyrrolidine IS. 

Magnesium, 235 Samarium(II) iodide, 270 Titanium(IV) chloride, 304 Addition reactions to carbonyl groups—Addition of functionalized CARBON NUCLEOPHILES (see also Aldol reaction and other specific condensation reactions, Meth-ylenation, Peterson Olefination, Refor-matsky reaction, Wittig reaction, Wittig-Horner reaction)... 

This topological rule readily explained the reaction product 211 (>90% stereoselectivity) of open-chain nitroolefins 209 with open-chain enamines 210. Seebach and Golinski have further pointed out that several condensation reactions can also be rationalized by using this approach (a) cyclopropane formation from olefin and carbene, (b) Wittig reaction with aldehydes yielding cis olefins, (c) trans-dialkyl oxirane from alkylidene triphenylarsane and aldehydes, (d) ketenes and cyclopentadiene 2+2-addition, le) (E)-silyl-nitronate and aldehydes, (f) syn and anti-Li and B-enolates of ketones, esters, amides and aldehydes, (g) Z-allylboranes and aldehydes, (h) E-alkyl-borane or E-allylchromium derivatives and aldehydes, (i) enamine from cyclohexanone and cinnamic aldehyde, (j) E-enamines and E-nitroolefins and finally, (k) enamines from cycloalkanones and styryl sulfone. 

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