Alkenes stereoselective formation

With sulfur and triethylamine in dimethylformamide, compounds (86) give (89) (Equation (21)) <89JPR243>. With thiols or KjS, sulfides are produced (e.g., (90) and (91)), which show spasmolytic activity in vitro <86MI 404-01 >. Smooth 5N2-displacements of chlorine occur with phenol, thiophenol, SCN, and thiourea in dimethylsulfoxide. However, with K2CO3 or sodium cyanide, (86) (Ar = Ph) affords the trimers (92) or (93) (Scheme 32). With electron-deficient trans alkenes, stereoselective formation of cyclopropanes (94) was observed (Scheme 32). No reactions occur with maleates <66HCA412>. 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

The utility of lOOC reactions in the synthesis of fused rings containing a bridgehead N atom such as pyrrolizidines, indolizidines, and quinolizidines which occur widely in a number of alkaloids has been demonstrated [64]. Substrates 242 a-d, that possess properly positioned aldoxime and alkene functions, were prepared from proline or pipecolinic acid 240 (Eq. 27). Esterification of 240 and introduction of unsaturation on N by AT-alkylation produced 241 which was followed by conversion of the carbethoxy function to an aldoxime 242. lOOC reaction of 242 led to stereoselective formation of various tricyclic systems 243. This versatile method thus allows attachment of various unsaturated side chains that can serve for generation of functionalized five- or six-membered (possibly even larger) rings. 

Although early works have reported variable yields and substrate dependence, a marked tendency to stereospecificity has been noticed. For example, the reaction of the trans epoxysilane 176 (Scheme 74) with lithium reagents results, after Si-Li exchange, electrophilic trapping of the resulting lithiooxirane by RLi and Li20 elimination, in the stereoselective formation of an E) alkene in good yield. ... 

The most active heterogeneous catalysts that are effective at room temperature are alkali metals supported on activated alumina. Simple C4-Cg alkenes, for example, were shown to yield equilibrium mixtures in short contact time over sodium on alumina.112116 Partial conversion of 1-butene at low temperature and in very short contact time (—60°C, 14 s) led to the stereoselective formation of m-2-butene.112 The changes in isomeric composition in the transformation of 4-methyl-l-pentene112 are as follows ... 

Not readily reconcilable with these models is the finding by Calderon and coworkers, who observed that cw-4-methyl-2-pentene, a hindered alkene, underwent a faster isomerization than metathesis21 92 (formation of 40% trans isomer at 4% conversion). The most striking feature of the transformation is the highly stereoselective formation of trans-2,5-dimethyl-3-hexene throughout the course of reaction regardless of the structure of the starting alkene ... 

Sometimes, alcohols can direct the oxidation of alkenes, resulting in highly stereoselective formation of tetrahydrofurans by the action of Collins reagent. Thus, 1,2-diols can form cyclic chromate esters that can intramole-cularly oxidize alkenes, positioned so as to allow the operation of five-membered cyclic transition states.119... 

The important feature is that no exceptional, contrived, or unprecedented chemistry has to be invoked to rationalize the stereoselective formation of the cw-alkene preferential rapid hydronation of the metal (or binding of an alkyne to a preformed hydrido species) naturally results in the c/s-alkene. 

Fig. 4. 26. anti -Selectivity of an E2 elimination as a reason for the stereoselective formation of a Z- instead of an F-configured alkene. 

The photochemical reaction of carbonyl compounds and alkenes, which is referred to as the Paterno-Buchi (PB) reaction, was developed in 1909 [13], and is currently one of the most widely used methods for oxetane synthesis (Scheme 7.4). As exemplified in the PB reaction of benzophenone with 2-methylpropene [14], a selective formation of the oxetane is possible even when the photochemical reaction involves highly unstable molecules that is, the excited state of carbonyls. Due to its synthetic importance and mechanistic interest, the PB reaction is the most extensively studied synthetic method for oxetanes. Thus, several extensive reviews describing the PB reaction have been published since 1968, and the reader is directed towards these for further information [15]. In this chapter, methods that allow for the control of the regioselective and stereoselective formation of synthetically important oxetanes will be described. 

With the same methodology, the preparation of 3-phenyl-substituted THFs can be assessed by irradiating ArCl in the presence of a nonterminal alkene. Hence, the photogenerated phenyl cations react with the (E)-3-hexen-l-ol, and this results in the stereoselective formation of traws-2-ethyl-3-aryltetrahydrofuran derivative in good to very good yields (52-88%) [72],... 

The acid or base elimination of a diastereoisomerically pure p-hydroxysilane, 1, (the Peterson olefination reaction4) provides one of the very best methods for the stereoselective formation of alkenes. Either the E- or Z-isomer may be prepared with excellent geometric selectivity from a single precursor (Scheme 1). The widespread use of the Peterson olefination reaction in synthesis has been limited, however, by the fact that there are few experimentally simple methods available for the formation of diastereoisomerically pure p-hydroxysilanes.56 One reliable route is the Cram controlled addition of nucleophiles to a-silyl ketones,6 but such an approach is complicated by difficulties in the preparation of (a-silylalkyl)lithium species or the corresponding Grignard reagents. These difficulties have been resolved by the development of a simple method for the preparation and reductive acylation of (a-chloroalkyl)silanes.7... 

Syn hydroxylation from the more hindered face of a ir-system can be effected using Woodward s pro-cedure in which an alkene is treated with iodine-silver acetate in acetic acid containing water. Variants of this method avoid the use of silver salts.A versatile pocedure by which syn hydroxyla-tion can be performed on either the more hindered or less hindered face of an alkene relies on stereoselective formation of the appropriate traru-bromohydrin from the alkene. ... 

The early woric with thiyl radicals primarily involved the intramolecular cyclization of alkenes. The reaction appears to be useful since high yields and stereoselective formation of products are observed (equation 7). Under a variety of conditions the diallyl diester (12) produces a 6 1 mixture of stereo-isomeric cyclopentanes (13) and (14) in high yield. ° When enynes are treated with thiyl radicals, low to moderate yields of addition products are observed (equation 8). ... 

The stereoselective formation of /3-hydroxy selenides has also been reported 36 in the reaction of alkenes with, V-(phenylseleno)phthalimide or the succinimide derivative in aqueous acetonitrile or dichloromethane. The use of phenylselenenyl chloride under these conditions gives similar results (Table 5)37. 

The reactions leading to stereoselective formation of the C — Si bond fall into two main categories hydrosilylation of alkenes or dienes (cf. Houben-Weyl, Vol. 13/5, p 51) and the related addition of silyl anions to activated C-C double bonds (cf. Houben-Weyl, Vol. 13/5, p 53). Also of interest is the stereoselective silylation ofcarbanions (cf. Houben-Weyl, Vol. 13/5, p 39). 

A method for the hydrocyanation of alkenes and alkynes is based upon hydrozirconation followed by isonitrile insertion (Scheme 13) overall yields range from 45-90%. Certain examples do not exhibit the clean regiochemistry represented here, and these were discussed in Section 3.9.3.3.2. The hydrozirco-nation/protonolysis of equation (53) results in high yield, stereoselective formation of C-methyldeoxy-sugars, an alternative to free radical deoxygenation. ... 

Mizorokf and Heck reported independently in the early 1970s the first palladium-mediated coupling of an aryl or vinyl halide or triflate with an alkene. This reaction is generally referred to as the Heck reaction. From the first reports on asymmetric intramolecular Heck reactions by Overman and Shibasakf in 1989 the asymmetric Heck reaction has emerged as a reliable method for the stereoselective formation of tertiary and quaternary stereogenic centers by C-C bond formation in polyfunctionalized molecules. ... 

Revision of three main methods for stereoselective (or specific) alkene bond formation. 

The catalyst activity decreased with increasing polymer crystallinity. A high regioselectivity of the catalyst in the hydrosilylation of alkenes towards formation of the linear products was achieved due to the favorable microporous structure of the polyamide supports with pore size of 10-20. The stereoselectivity of the reaction can be reversed by a proper choice of donor functions in a polymer support, for example the traditional cis-selectivity of Rh catalysts in hydrosilylation of phen-ylacetylene was changed to trans-selectivity by use of a 2,5-py instead of a 2,6-py moiety. The polyamide-supported catalysts showed high stability through 6-9 synthesis runs [25]. 

Certain carbobicyclic rings systems can also be constructed in a stereoselective fashion using this approach. The stereoselective formation of diquinanes and hydrindanes, in which the relative stereochemistry between three contiguous stereogenic centers is controlled, has recently been reported152 135. Photolysis of 4-pyranone 36 presumably affords the intermediate ally-loxy zwitterion 37. Capture by a pendant alkene leads to formation of the diquinane 38. 

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