Stereoselectivity transannular cyclizations

Stereoselective transannular cyclizations to hydroazulene systems are also described. These reactions are initiated by ionization of cyclodecenol to form an allylic cation or by oxirane ring opening in cyclodecadiene monoepoxides. 

Transannular cyclizations of nine-membered cyclic sulfides provided a novel route to thioanalogues of swainsonine derivatives. Treatment of the enantiopure polyhydroxylated thiacyclononane derivative 48a with trimethylsilyl iodide yielded the bicyclic sulfonium salt 49a as a single diastereomer, as shown in Equation (16) <2003JOC3311 >. The presence of a C2-axis and the complete regio- and stereoselectivity of the transannular substitution led to a single configurationally homogeneous product irrespective of the fact that the sulfur atom would attack C-5 or C-6. 

Ikegami has devised an interesting approach based upon 1,3-cyclooctadiene monoepoxide as starting material (Scheme LX) Transannular cyclization, Sharpless epoxidation, and silylation leads to 638 which is opened with reasonable regioselec-tivity upon reaction with l,3-bis(methylthio)allyllithium. Once aldehyde 639 had been accessed, -amyllithium addition was found to be stereoselective, perhaps because of the location of the te -butyldimethylsilyloxy group. Nevertheless, 640 is ultimately produced in low overall yield. This situation is rectified in part by the initial formation of 641 and eventual decarboxylative elimination of 642 to arrive at 643. An additional improvement has appeared in the form of a 1,2-carbonyl transposition sequence which successfully transforms 641 into 644... 

Stereoselective radical cyclization of 1,5-cyclooctadienes. Winkler and Sridar14 have noted transannular effects on the stereochemistry of cyclization of these octadienes (equation I). Thus radical cyclization of cis-1 and of the corresponding ketone (3) is highly frans-selective and is more rrans-selective than that of the monosubstituted diene 5. Cyclization of a 3,8-disubstituted cyclooctene is... 

When the substituent in 10 at C2 is a carboxaldehyde group, i.e. 10b, this cationic cyclopropana-tion reaction was accompanied by transannular cyclization to form a mixture of regiomeric olefins 12b. However, a selective reaction occurred with 10a on silylation with trimethylsilyl triflate in toluene at — 20 °C and subsequent desilylation with potassium fluoride in methanol a mixture of olefins 12a was obtained in 80% yield. Applying these conditions to 10b did not lead to 12 b. Instead, efficient transannular cyclization took place to form the 3,6-secoprotoil-ludane system. These reactions are examples of a regio- and stereoselective transformation of the humulene skeleton into cyclohumulanoids. 

E,E)-. 6-Cyclodecadienone undergoes a transannular cyclization in the presence of mercuric acetate to form rram-decalins. Mixtures of products are found due to the nonselective termination reaction which consists of a nonregioselective proton elimination but stereoselective attack of the hydroxide ion16. 

The regio- and stereoselectivities of the anionic transannular cyclization of (Z)- and ( )-epoxy-sulfones (149) have been studied (Equation (8)) <9iJOC45i3, 92JOCi457>. The proportion of regio-isomeric products (150) and (151) was found to depend on the mode of metallation. 

The bicyclic ethers 277 and 278 are obtained by a transannular oxidative cyclization using HTIB. Although this reaction shows poor regioselectivity, the addition to the double bond proceeds with high trans stereoselectivity (87TL5229) (Scheme 70). 

Several detailed investigations of transannular IMDA cycloadditions have appeared in recent years. This transformation promises to become an important synthetic method owing to the potential for the rapid efficient construction of complex polycyclic ring systems. Other potenti strategic benefits include increased reactivity due to diminished entropic requirements (AS ). This is nicely illustrated by the facile cyclization of (101) with a tetrasubstituted dienophile, compared with the unsuccessful IMDA reaction of (102) (Figure 27). Although the cyclization of (101) proceeds with only moderate diastereoselection, many other examples have been reported that exhibit outstanding selectivity, e.g. cyclization of (103). It is conceivable that conformational constraints imposed by the macrocyclic system may lead to improved IMDA stereoselectivity relative to conventional acyclic trienes, but this point has not yet been demonstrated in any published examples. 

The synthesis of hydrazulene-type sesquiterpene lactones such as 253 have attracted considerable efforts for many years [86]. The current approach features an acetal-silylenolether cyclization as present in precursor 250 [87]. Under the mediation of titanium tetrachloride the desired seven-membered ring is closed to form compound 252, which eliminates methanol to give the hydrazulene 253. The crucial issue is the stereoselective introduction of the methyl group at the 5,7-ring fusion. This is achieved at the stage of enone 249, which adds dimethyl cuprate stereoselectively to give 250. A plausible explanation Hes in the formation of complex 254, which delivers the copper transannularly to the syn-face of the cyclopentenone in the extended conformation shown. 

One early example was reported by Chatteijee in 1979 for stereospecific synthesis of the sesquiterpene isocomene by transannular cationic cyclization. The acid-catalyzed cyclization of epoxide 152 through transannular participation of the remote double bond led to the formation of 153 (Scheme 20.37), which was further transformed to isocomene. The reaction was stereoselective since formation of any other diastereomers will lead to the formation of much strained polycyclic systems with trans-fased cyclopentanes. 

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