Thio-Wittig reactions

The first reliable evidence for the formation of thiabetaines (+)P-C-C-S( ) as true intermediates in thio-Wittig reaction was obtained11-13 only after the synthesis and complete characterization of the corresponding thiabetaines I of the silicon series.14,15 This evidence was based on the resemblance of the spectral parameters of compounds of both series.11... 

Tellurium sources, 22-24 Thermodynamics in cyclo-oligomerization, 185-186 butadiene insertion, 187-188 reductive elimination, 193, 194 selectivity control, 212 polysilane isomerisation, 158-160 see also Stability Thermolysis, 135, 136, 158 THF (tetrahydrofuran), 97, 150, 153 Thio-Wittig reaction, 37 Tin, 121... 

The thio-Wittig reaction, like the Wittig itself, may involve (thia)phosphetane or betaine-type structures as intermediates. A combined experimental and theoretical study over a wide range of conditions and of substrates (aliphatic vs aromatic, aldehyde- vs ketone-derived) suggests a mechanistic continuity, with solvent polarity and substrate electronic effects being the main influences on the transition from one mechanism to another. ... 

Carbanions stabilized by phosphorus and acyl substituents have also been frequently used in sophisticated cyclization reactions under mild reaction conditions. Perhaps the most spectacular case is the formation of an ylide from the /7-lactam given below using polymeric Hilnig base (diisopropylaminomethylated polystyrene) for removal of protons. The phosphorus ylide in hot toluene then underwent an intramolecular Wittig reaction with an acetyl-thio group to yield the extremely add-sensitive penicillin analogue (a penem I. Ernest, 1979). 

The thio-Wittig reaction between thioaldehyde and phosphorus ylides yields initially a thiaphosphetane, which undergoes cycloreversion to a P=S bond444. 

Whereas the thio-2,3-Wittig reaction is well recognized and used, particularly in terpene synthesis e.g. Scheme 49), the amino counterpart is less studied. 

Due to the hindered nature of the oxo group in these compounds the Wittig reaction is of limited use and a much more flexible route to the 4-alkylidene derivatives is through the 4-diazo and 4-thio compounds 22 and 23. 

In an attempt to increase the Wittig-type reactivity of amide derivatives the reaction of phosphonium ylides, e.g. (91), with thioimides, e.g. (92) and (93), has been investigated.49 Although the thio-Wittig reaction takes place, S-alkylation and oxidation-reduction occur in competition and reduce the usefulness of this reaction in synthesis. Further studies of the reactions of a-perfluoroacylalkylphosphonium salt (94),50.51 generated by... 

The (S)-lactone acid 1, obtained from L-glutamic acid by nitrous acid deamination, was converted to the acid chloride, then treated with excess diazomethane followed by hydrogen iodide to yield the keto-lactone 2. Amidation occurred quantitatively to give the partially racemized amide 3, which was purified by repeated recrystallizations. The vicinal diol resulting from reaction with excess methylmagnesium iodide was protected as the acetonide 4. An isomeric mixture of olefins (Z , 26 74) was obtained from the subsequent Wittig reaction. Reduction followed by separation on silver nitrate coated silica gel gave the (Z)-and ( )-alcohols in 20% (6) and 61% (5) yield, respectively. Conversion of the (S)-( )-alcohol (5) to the chloride then afforded the thioether (7) on reaction with sodium phenylsulfide. The thio ether anion was formed by treatment with n-butyllithium. Alkylation with the allylic chloride" (8), followed by removal of sulfur, then yielded the diene 9, which was converted in several steps to (/ ) (-t-)-10,11 -epoxy famesol. 

Dienes, as the simplest polyene systems, are widely encountered in sex pheromones like (4E, 7Z)-4,7-tridecadienyl acetate (100), a component of the sex pheromone of the potato tuberworm moth (Phthorimaea operculella). This compund was synthesized by Kim and Park [54] starting from a protected 5-hexen-l-ol and utilizing the chemistry of thio-substituted phosphonates (Scheme 28). Thus, the Pummerer rearrangement of a-phosphoryl sulfoxide 101 with 5-hexenyl acetate 102 afforded 7-acetoxy-l-methylthiohept-3-enyl phos-phonate 103 as an E/Z=85 15 mixture, being unreactive in the Horner-Wittig reaction, even after OAc deprotection/THP reprotection. However, the reaction of the more reactive a-phosphoryl sulfone 104 with w-hexanal successfully led to the required 1,4-diene 105, as an ElZ = 70 30 mixture, in 86 % yield. The final pheromone 100 was obtained after the desulfonylation of 105 with sodium hydrosulfite and the OTHP OH OAc deprotection/reprotection procedures. 

When compounds 298, using a stoichiometric amormt of diphenylke-tene or methylphenylketene, were subjected to Aza—Wittig reactions, N-[2-alkyl(aryl)thiocarbonyl]phenyl ketenimines 299 was obtained. A/-[2-(Alkyl- or arylthio)carbonyl]phenyl keteriiniines 299 was cychzed under mild thermal conditions to give 2-alkyl(aryl)thio-3H-quinohn-4-ones... 

Displacement of Sulphur. The Wittig reaction of resonance-stabilized phosphorus ylides with thioacyl-urethanes gives acylated enamines, e.g. (84), from which )ff-keto-esters are obtained by hydrolysis. Hydrazine displaces sulphur in thioanilides, giving amidrazones, but with two equivalents of arylselenoamides it gives 2,5-diaryl-1,3,4-selenadiazoles. Selenoamides react with an excess of hydrazine to give 1,2,4,5-tetrazines (see also Chap. 6, p. 294). l,2-Bis(thio-benzamido)ethane, when treated with NEt, and HgO, cyclizes to 2-phenyl-... 

New syntheses of ( )-clavulanic acid and its thio-analogue have appeared. The synthesis of the latter compound makes use of yet another internal Wittig reaction (Scheme 136), and it is readily converted into a penem. 

The final example of a domino process under high pressure, to be discussed in this chapter, is a combination of a Horner-Wittig-Emmons (HWE) reaction with a Michael addition developed by Reiser and coworkers [5]. Hence, reaction of a mixture of an aldehyde such as 10-18, a phosphonate 10-19 and a nucleophile 10-20 in the presence of triethylamine at 8 kbar led to 10-21. By this method, (3-amino esters, 3-thio esters and 3-thio nitriles can be prepared in high yield (Scheme 10.4). Many of these transformations do not occur under standard conditions, thereby underlining the importance of high pressure in organic chemistry. 

The pioneering work on thia-[2,3]-Wittig rearrangement was reported by Rautenstrauch in 1971 °. The reaction of allyl sulfides 137 with n-BuLi at —30°C for 1.5-4 h gave homoallyl sulfide or thiol 138 ([2,3]-product) exclusively (equation 81). In contrast, a similar reaction of vinyl sulfide 139 gave no [1,2]-rearrangement product 141 albeit a-thio-carbanion was generated as shown by its methylation to 140 (equation 82) °. 

For the Thio-[2,3]-Wittig Rearrangement, Nakai reported the following relative reaction rates R = Ph > C02Li > CN > C02Et > COMe, and for R = Ph > H > CH3. Reactions in this series were conducted at temperatures of from -80 °C to +60 °C. 

A review on the chemistry of thio derivatives of trivalent phosphorus acids which covers the literature to 1986, includes a section on pentaco-ordinate phosphorus compounds derived from addition to a-diketones and unsaturated systems activated to nucleophilic attack by electron withdrawing groups. Chemical bonding in hypervalent molecules has been discussed and qualitative bonding concepts developed to supersede the dsp and d sp models. A review on the mechanism and stereochemistry of the Wittig olefination reaction inevitably includes a discussion of the equilibrium between betaine and 1,2-oxaphosphetane intermediates. A correction has been published to reference 19 of Chapter 2 in SPR14, Vol.21, concerning the Mitsunobu Reaction. ... 

---