Trans styrenes, synthesis

PdCl2(CH3CN)2-catalyzed Z to E isomerization of arylalkenes constitutes a reliable and mild method for the preparation of geometrically pure trans-styrene derivatives from the corresponding ds-alkenes or alkene mixtures (eq 49). This protocol has found applications in natural product synthesis, as in the case of (—)-rodgersinol. ... 

Baldwin et al. have used the same catalyst/diazo ester combination for the synthesis of optically active deuterated phenylcyclopropanes (Scheme 28) 197). From cis-1,2-dideuteriostyrene, d/-menthyl a-deuteriodiazoacetate and (+)-195d, the cis- and mnw-cyclopropanes 196 were obtained, both with 90% optical purity. The dominant enantiomer of trans-196 had (+)-(15, IS, 35) configuration. Analogously, the cyclopropanes c -198 and trans-198, obtained from styrene, d/-menthyl a-deuteriodiazoacetate and (+)-195d with subsequent transesterification of cisjtrans-197, had optical purities of 86 and 89%, respectively. The major optical isomer of cis-198 had (IS, 2R) configuration, that of trans-198 (IS, 2S) configuration. 

During the past 2 years several research groups have published research that either uses or expands upon Crowe s acyclic cross-metathesis chemistry. The first reported application of this chemistry was in the synthesis of frans-disubstitut-ed homoallylic alcohols [30]. Cross-metathesis of styrenes with homoallylic silyl ethers 15, prepared via asymmetric allylboration and subsequent alcohol protection, gave the desired trans cross-metathesis products in moderate to good yields (Eq. 15). 

So, in this instance, cyclopropane formation is the first rather than the last step in the synthesis. Addition of ethyl diazoacetate 42 R = Et to styrene 41 gave a mixture7 of cis and trans isomers of 40 R = Et. Only the cis isomer will be able to cyclise so separation8 of the free acid gave 34% yield of cis-43. Chain extension by the Amdt-Eistert procedure9 (chapter 31) gave cis-35 and the acid chloride duly cyclised to 36. 

Other alkenyl iodonium salts which furnished functionalized dienes had a cyclo-hexenyl, a 2-(tosyloxy)hexenyl or a tosyloxyvinyl moiety the unsaturated partners included propenal, methyl acrylate and styrene. The yields were consistently high (64-85%) and the stereoselectivity invariably trans. An alternative method for the synthesis of dienes involved alkenyl stannanes such as CH2=CHSnBu3, E-PhCH=CHCH2SnBu3 and CH2=CHCH2SnBu3 [38]. Several alkynylstannanes afforded similarly enynes in good yield [39]. 

More detailed isotopic labeling studies have also been performed. Hydroxycyclopropanation of trans-f.3-deutero-styrene 273 under Kulinkovich conditions furnishes m-2-phcny 1-1 -cyclopropanol, 274, indicating retention of configuration at the carbon bound to titanium and is consistent with frontside attack of the Ti-C bond on a titanium-bound carbonyl.220 For the related de Meijere cyclopropylamine synthesis, the opposite outcome has been observed where a 3 1 mixture of A, Wdimethyl-W(/ra t-3-deutero-/ra j-2-phenylcyclopropyl)amine 278 and -dim ethyl-. V-((7.i-dcutcro-t7r-2-phony Icyclopropy I )amine 277 is produced. These products require inversion of configuration at the carbon bound to titanium and are consistent with a W-shaped transition structure for ring closure (Scheme 46). 

The direct transfer of carbene from diazocompounds to olefins catalyzed by transition metals is the most straightforward synthesis of cyclopropanes [3,4]. Reactions of diazoesters with olefins have been studied using complexes of several transition metals as catalysts. In most cases trans-isomers are preferably obtained, but the selectivity depends on the nature of the complex. In general the highest trans-selectivity is obtained with copper catalysts and it is reduced with palladium and rhodium complexes. Therefore, the rhodium mesotetraphenylporphyrin (RhTPPI) [5] and [(r 5-C5H5)Fe(CO)2(THF)]BF4 [6] are the only catalysts leading to a preference for the cis-isomer in the reaction of ethyl diazoacetate with styrene. 

Nair and co-workers [8] have coupled of semi-continuous NF with the Heck reaction. The objective was the synthesis of trans-stilbene from styrene and iodobenzene using Pd(OAc)2(PPh3)2 as catalyst and Pjo-tolyljj as stabilizing agent. They used solvent-resistant membranes and different aqueous/solvent systems (ethyl acetate and acetone/H20 methyl tert-butyl ether and acetone/H20 tetra-hydrofuran/H20). The best conversion was obtained with the first-mentioned solvent mixture. A selectivity of 100% of trans-stilbene with a cumulative turnover number of 1200 was reported, where the rejection of the catalyst turned out to be as high as 97%. Therefore, the authors concluded that NF was a convenient technique to run catalytic reactions with catalyst recycling, since this method saves the catalyst, prevents the metal contamination of the products, and increases reactor productivity. 

The tosylation of carbon can be accomplished using electron transfer conditions. Treatment of styrene and analogs with Copper(II) Chloride and tosyl chloride or Benzenesulfonyl Chloride results in a formal replacement of the vinyl proton by the sulfonyl moiety (eq 35). The intermediacy of a trans-(S-chloro sulfone has been demonstrated by H NMR. Treatment with base induced the elimination of HCl. A variety of other sulfonyl transfer reagents can be ertployed in the synthesis of isolated /3-chloro sulfones, with good results (60-97% yield) for a variety of alkenes (ethylene, 1-butene, 2-butene, 1-octene, acrylonitrile, methyl acrylate, and 1,3-butadiene). ... 

Frauenkron and Berkessel [181], and Che et al. [171], independently reported that the ruthenium complex of the same chiral porphyrin, can be used to catalyze the cyclopropanation of styrene. The synthesis of this chiral porphyrin was previously reported by Halterman and Jan [ 176[. This reaction is particularly interesting since the enantiomeric excesses are quite high (90%). Surprisingly, changing the solvent from 1,2-dichloroethane to benzene resulted in an inversion of the absolute configuration of the major enantiomer for the ds-cyclopropane and no change for the trans-cyclopropane [181]. 

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