Carbonate cyclization, homoallylic

J(P1)427>. The regioselectivity of the second radical cyclization depends on the electronic nature of the homoallylic double bond pyrrolizinones 240 which result from a final 5-o -cyclization mode are preferred in the case of electron-poor carbon-carbon double bonds, such as enones or enoates electron-rich double bonds lead to indolizinones via a final 6-f db-cyclization. The best yields of pyrrolizinones were observed with iodide precursors. The cir-isomers of 240 predominate in this 5-f rf6i-5-f3co-cyclization. 

Cyclofunctionalization of homoallylic alcohols with bis(sym-collidine)iodine(I) perchlorate produces oxetanes in good yield if the 4-exo mode of cyclization is favored electronically by the alkene substitution pattern (Table l).14 Geminal substitution at the carbinol carbon also favors this mode of cyclization (compare entries 2 and 3 with entry 1). Substitution at C-3 leads to reaction only by the 4-exo mode (entry 4), while substitution at C-4 leads to cyclization only via the 5-endo mode (entry 5). 

Homoallylic alcohols with a silyl group attached to the terminal alkene carbon were cyclised to oxetanes in high yields by reaction with bis(.sy z-collidine)bromine(l) hexafluoroantimonate (e.g., Equation 31) <2001TL2481>. This reaction exclusively gave the four-membered cyclic ether, with the silyl group directing formation of the electrophilic intermediate for the subsequent 4-fvo-/rrg -cyclization. When the carbon /3 to the silyl group on the double bond was unsubstituted, the reaction was diastereospecific. 

On the other hand, when iodine monobromide in toluene at low temperature was employed to induce the cyclization of secondary rm-butyl homoallyl carbonates, very high 1,3-asymmetric induction was observed, leading mainly to the ris-isomer11, l2. 

In a similar way, 2-oxazolidinones and tetrahydro-2//-l, 3-oxazin-2-ones have been prepared by the reaction of primary allyl amines and homoallyl amines10, respectively, with carbon dioxide and iodine in methanol via an intramolecular cyclization. Prolonged reaction for a week in the presence of cesium carbonate increases the yield to 70-90%. This reaction has a large applicability and the ease of the method makes it useful in organic synthesis. 

Zinc-mediated Barbier-t) e addition of 238, followed by Luche s procedure obtained a mixture of the homoallylic alcohol diastereomers 239 and 240. Alcohol 239 was carried through benzoylation, deketalization, silylation, and ozonolysis, to produce C-branched y-lactone 241. Benzoylation of 240 followed by hydroboration, PCC oxidation, debenzoylation, and alkaline-promoted cyclization directly formed C3-branching 2-deoxyfuranose 242 [87] (O Scheme 63). A novel method for stereoselective synthesis of 4 -a-carbon-substituted nucleosides, through epoxidation of 4, 5 -unsaturated nucleosides and SnCU-promoted epoxy ring opening, was... 

Various types of [3 + 0] cyclizations via y-functionalized metal alkyls (either as stable compounds or reactive intermediates) are known. The y-carbon can act as an acceptor, a donor or radical center. Homoallyllic systems 1 can cyclize via alkene insertion to form (metallamethyl)cyclo-propanes 2. 

The a-siloxyalkyl radical intermediate can be used for carbon-carbon bond formation by intra- and intermolecular trapping (Scheme 10.233). In the BUjSriH-mediated system, a bromoalkenoylsilane is efficiently converted into a bicyclic compound by tandem radical cyclization [601]. When allyltributylstannane is used instead of BuaSnH, the a-siloxyalkyl radical generated from a 5-bromoalkanoylsi-lane undergoes homolytic allylation to provide a homoallyl silyl ether [602]. 

Diastereoselective cyclization of homoallyl carbonates The conversion of the carbonate I to 2 has traditionally been effected with l2 in CHjCN at —20°. It can be carried out with higher selectivity with IBr in toluene, particularly at temperatures of... 

In the cyclization reactions of homoallylic ethers and higher homologs, alkoxymethyl radicals play a prominent role [26]. Substrates like 28 supply more useful carbon-centered radicals enjoying captodative stabilization, and trany-2,3-disubstituted tet-rahydropyrans were prepared stereoselectively with judicious modification of the double bond in the substrate [27] (Scheme 12). The same radical species from the substrate 30 was reported to give the oxocane 31 via the xanthate transfer %-endo cyclization, from which lauthisan (32) was obtained [28] (Scheme 13). 

Cyclization. It is sometimes advantageous to use this reagent for the halogen-induced alkene functionalization with participation of an internal nucleophile. At low temperatures homoallylic carbonates react with enhanced diastereoselectivity. 

More sophisticated examples are provided by substitution reactions, which are influenced by a remote double bond. The 3p-hydroxy group of cholesterol, for example, can be substituted by chloride with PClg or, after tosylation, by methoxide. In both cases almost quantitative yields of p-substituted compounds are observed. All 3P-hydroxy steroids with a 5,6-double bond give these reactions. The homoallylic carbonium ion at G3 and its cyclization after neuttaliza-tion at the y carbon atom have thus been established as well as the thermodynamic preference of equatorial substitution in cyclohexane units (Scheme 3.4.2). 

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