Sulfides, homoallylic alkylation

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. 

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). 

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]. 

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). 

Alkylated thioaldehydes, generated by Pummerer reanangements or treatment of a-chloro sulfides with SnCU, undergo ene type reactions with terminal alkenes to give homoallylic sulfides in 50-70% yield (equation 20). ... 

Another series of -alkyl-metal complexes that owe their stabilities to the formation of a five-membered chelate ring is those produced in the reaction of allylic and, homoallylic amine and sulfide complexes of Pd(II) with nucleophiles. Lithium tetra-chloropalladate reacts with N,N-dimethylallylamine in methanol to produce the methoxy- kalkylPd complex ... 

A closely related reaction has been developed on homoallylic amines and sulfides. These substrates undergo regiospecific carbopalladation in the presence of stabilized enolates and lithium tetrachloropalladate to provide stable five-membered paUadacycles. Reduction of the complexes 9 and 10, respectively, affords the alkylated diester 11 and keto ester 12 (Scheme 8). 

The cyclopalladation of allylic or homoallylic amines and sulfides proceeds due to the chelating effect of N and S atoms, and has been used for functionalization of alkenes. For example, i-propyl 3-butenyl sulfide is carbopalladated with methyl cy-clopentanecarboxylate and Li2PdCl4. Reduction of the chelated complex with sodium cyanoborohydride affords the alkylated keto ester in 96% yield (eq 24). Functionalization of 3-N,N-dimethylaminocyclopentene for the synthesis of a prostaglandin skeleton has been carried out via a IV-chelated palladium complex as an intermediate. In the first step, malonate was introduced regio- and stereoselectively by carbopalladation (eq 25). Elimination of a /3-hydrogen generated a new cyclopentene, and its oxypalladation with 2-chloroethanol, followed by insertion of 1-octen-3-one and /3-elimination, afforded the final product. 

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