Intramolecular cycloadditions diastereoselectivity, asymmetric reactions

Winkler has extensively examined stereoselective (2 + 2]-cycloaddition reactions in the context of complex molecule synthesis (see also Scheme 18.36). In a fundamental study, intramolecular cycloadditions of tethered enones proved to be highly diastereoselective. Thus, the presence of the stereogenic center on the tether connecting the enone to the dioxinone in 198 controls the stereochemical outcome of the reaction as shown in Scheme 18.31 [133,134). Cycloadduct 200 was isolated in 95 % yield and with superb levels of asymmetric induction (dr= 95 5). A subsequent fragmentation sequence transformed 200 into the neurotoxin perhydrohistrionitoxin (201), an alkaloid isolated from neotropical poison frogs [134]. 

Our initial improvement in the synthesis of pyrrolidine acid 3 relied on a racemic 1,3 dipolar cycloaddition followed by resolution. Attempts to devise asymmetric protocols of this reaction using chiral auxiliaries were not productive. The results from our laboratories were consistent with literature findings, with a moderate diastereoselectivity of 3 to 4 1 at best obtained even when double chiral auxiliaries were used. Several other approaches, such as Aza-Cope/Mannich reaction, intramolecular C-H insertion, and asymmetric aryl 1,4 addition, did not bear fruit. 

The synthesis of seven-membered rings from furans and a,a -dibromoketones via oxyallyl intermediates is well known. It was reported that this reaction occurs quite easily when water is used as solvent <97TL8031>. In a study on the influence of steric and electronic effects on a function attached at C-2 of furans in the yield and diastereoselectivity of [4 + 3] cycloaddition reactions with oxyallyl cations it was found that in almost all cases a c/x-diastereospecificity and a high endo diastereoselectivity is obtained <97T11669>. A tandem Peterson olefination-[4 + 3] cycloaddition reaction with furans has been reported <97JOC1578 97TL386l>. For an intramolecular [4 -t- 3] cycloaddition see <97JOC6051>. The first asymmetric [4 + 3]... 

Trost et al. reported the first asymmetric total synthesis of pseudolaric acid B by exploiting a rhodium-catalyzed intramolecular [5-1-2] cycloaddition reaction of a vinylcyclopropane with an alkyne (Scheme 8.2) [4]. The vinylcyclopropane having a tethered alkyne moiety 12 was synthesized from chiral precursors 9 and 11. Treatment of 12 with a cationic rhodium(1) catalyst promoted the [5-1-2] cycloaddition reaction to form a [5.3.0]bicyclic skeleton of 13 in a diastereoselective fashion. A few steps of functional group transformations provided the alkoxycarbonyl... 

The asymmetric synthesis of a symmetric [1 l]helicene-like molecule was accomplished by the cobalt-mediated diastereoselective double intramolecular [2 + 2 + 2] cycloaddition of a symmetric chiral hexayne possessing two stereogenic centers (Scheme 10.16) [8], Like the asymmetric synthesis of the [7]helicene-like molecules shown in Scheme 10.13, (5) centrochirality induced predominantly P) helical chirality in the reaction of the bulky p-tolyl-substituted hexayne. 

As one of the pioneering works on asymmetric synthesis, Evans and coworkers reported diastereoselective Diels-Alder reaction of acryloyl oxazolidinones mediated by Et2AlCl [140]. Intramolecular version of this cycloaddition was also reported, in which interesting stereochemical difference depending on substituents at oxazo-lidinone ring was found. As an another excellent example, Oppolzer and coworkers reported diastereoselective Diels-Alder reaction of chiral dienophiles equipped with camphorsultam auxiliary [141]. Recently, these diastereoselective reactions were applied to enantioselective synthesis of ceralure Bl, known as Mediterranean fruit fly attr actant (Scheme 6.118) [142]. 

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