Sulfides, homoallylic

The carbopalladation is extended to homoallylic amines and sulfides[466. Treatment of 4-dimethylamino-l-butene (518) with diethyl malonate and Li2PdCl4 in THF at room temperature leads to the oily carbopalladated complex 519, hydrogenation of which affords diethyl 4-(dimethylamino) butylmalonate (520) in an overall yield of 91%. Similarly, isopropyl 3-butenyl sulfide (521) is carbopalladated with methyl cyclopentanonecarboxylate and Li2PdCl4. Reduction of the complex affords the alkylated keto ester 522 in 96% yield. Thus functionalization of alkenes is possible by this method. 

Homoallyl ethers or sulfides.1 gem-Methoxy(phenylthio)alkanes (2), prepared by reaction of 1 with alkyl halides, react with allyltributyltin compounds in the presence of a Lewis acid to form either homoallyl methyl ethers or homoallyl phenyl sulfides. Use of BF3 etherate results in selective cleavage of the phenylthio group to provide homoallyl ethers, whereas TiCl effects cleavage of the methoxy group with formation of homoallyl sulfides. 

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) °. 

Unsaturated 1,5-dicarbonyl compounds. The phenylthioalkylation of silyl enol ethers of carbonyl compounds (9, 521-522) can be extended to the synthesis of unsaturated 1,5-dicarbonyl compounds. In a typical reaction the enol silyl ether of a ketone is alkylated with the unsaturated chloride 1 under ZnBr2 catalysis to give a homoallyl sulfide. Ozonolysis of the methylene group is accompanied by oxidation of the phenylthio group sulfoxide elimination results in an unsaturated 1,5-aldehydo ketone (equation I). Alkylation with 2 results in a methyl ketone (equation II). 

Further investigation of the equilibrium between titanacyclobutene and titanium vinyl alkylidene complexes, as discussed in Section 2.12.6.1.4, was reported recently <2007CEJ4074>, along with the incorporation of this reactivity pattern into the synthesis of conjugated dienes, homoallylic alcohols, vinylcyclopropanes, and phosphacyclobutenes from y-chloroallyl sulfides and a source of titanocene(ll). 

The basic Markovnikov selectivity pattern is partially or fully overrun in the presence of neighboring coordinating groups within the olefin substrate (Section 2.2.2). Known functionalities where inversed selectivity can occur include 3-alke-noylamides (e.g. 17 reacts to give a mixture of 18 and 19, Table 3) [43], homoallyl esters and alcohols, allyl ethers (but not necessarily allyl alcohols) [44], allyl amines, allyl amides, or carbamates (cf. 20 to 21) [45], allyl sulfides [46] or 1,5-dienes [47]. As a matter of fact, aldehyde by-products are quite normal in Wacker reactions, but tend to be overlooked. 

Very recently, Davies and coworkers have reported a silver-catalyzed Doyle-Kirmse reaction of ally lie and propargylic sulfides with ethyl diazophenylacetate (35). A selection of examples was investigated providing the rearranged products, either homoallylic thioethers (76 —> 77, Scheme 8.14a) or allenyl thioethers (78 —> 79, Scheme 8.14b) in good yields, and with good overall scope.40... 

Although allylic lithiation by deprotonation of non-heterosubstituted compounds is possible using superbases (see section 2.6), in most cases allylic lithiation requires a directing heteroatom. (Non-heterosubstituted allyllithiums are best produced by reductive lithiation of allyl ethers or allyl sulfides - see section 4.4.) One of the few cases where this heteroatom is not a to the new organolithium is shown below the p-lithiation of a homoallylic amide 137. The reaction is particularly remarkable because of the possibility of competing deprotonation... 

Phosphorus-functionalized homoallyl sulfides have been prepared using either base-promoted yUde generation [ 196] or, more recently, the carbenoid route (Scheme 84) [197]. When diazomethylphosphonate 341 [198] was reacted with allyhc sulfides 342, the rearranged a-phosphorylated sulfides 344... 

One of the first examples of an excellent stereoselectivity in open-chain allylic sulfides was published in 1986 by Weinreb [208]. In this remarkable paper a diastereoselective Diels-Alder reaction of a sulfinyl dienophile with a substituted diene delivered cycloadducts as described earlier (Sect. 3.5.3, Scheme 59). After ring opening and reduction Z-olefin 362 was produced which, after S-methylation and base treatment rearranged to isomerically pure homoallyl sulfide 363. 

Complex 376 can be prepared from enantiomerically pure rhenium precursor 381. The former can be deprotonated at low temperatures initiating the [2,3]-sigmatropic rearrangement to diastereomerically pure homoallylic sulfide complex 377. After S-alkylation, cyanide treatment releases the S ligand as product 379. As an extension of this work the authors showed that iron and ruthenium complexes can be used, too [219]. 

Thiazol-2-yl allyl sulfides react with organomagnesium compounds in the presence of CuBr to afford optically active alkenes in good yields and selectivities <1996T10799>. Thiazole and benzothiazole allyl sulfides have been shown to react with excess ethyl diazoacetate in the presence of a copper(i) hexafluorophosphate acetonitrile complex to give, via formation of the resultant homoallylic sulfide intermediates, conjugated dienoic esters in good yields <1997TL3289>. /3-Ketosulfides of benzothiazole 143 are very prone to deprotonation by weak bases. Treatment... 

Allyl-allyl cross-coupling of allyl bromides (Structure 1) and allyl sulfides (2) carrying homoallylic alcohol or ester functions takes place under irradiation with hexamethylditin (see eq. (1)). The reaction cleanly leads to 2,6-dienes (3) and no isomerization of allylic bromides is oberserved [56]. 

These reactions, coupl with the alkylations of sulfides and selenides, allow the homologation of primary alkyl halides - - - and the transformation of allyl halides to homoallyl halides. A related process, employing 2-methylthio- and 2-allylthio-thiazoline, allows the iodomeAylation (ICH2—) and the iodopropenylation (ICH2CH=CH—) of alkyl halides (Scheme 54).i3iii,i32.i7i... 

Cohen has used a soluble version of the Simmons-Smith reagent to promote the 3,2-rearrangement of allylic sulfides (Scheme 52). He has also applied this methodology to the synthesis of sarkomycin (225). The allylic sulfide (221), easily available via a Petrow reaction, was first alkylated and the sulfo-nium ylide was then generated by a fluoride-promoted desilylation. Rearrangement of the ylide (223) gave the homoallylic sulfide (224) which was eventually transformed into sarkomycin (Scheme 53). 

Allylation of a-thio-35), a-seleno-35) and a-silyl- 35,77) cyclopropyllithiums was not very successful35) but addition at —78 °C of 0.5 equivalent of copper (I) iodide-dimethylsulfide complex 35,106, W7> prior to the allylhalide leads 35,106,107) to a very high yield of homoallyl cyclopropyl sulfides or selenides (Scheme 24). Similar observations have been made on cyclobutyl derivatives3S). It is not clear at present whether a cuprate is involved in the process but we have evidence ( Se-NMR) that a new species is transiently being formed, at least in the seleno series. The synthesis of homoallyl cyclopropylsilanes was also reported 78) and involves the allylation of a postulated cuprate formed by the addition of lithium dibutyl cuprate to a-lithiocyclopropylsilane (Scheme 26). 

---