1.2.3.4- Tetrasubstituted cyclobutanes

The photochemical 2 + 2-cycloaddition of 2(5//)-furanones to symmetrical 1,4-disubstituted 2-butenes yielded 1,2,3,4-tetrasubstituted cyclobutanes with a high diastereo-selectivity. The ruthenium-catalysed 2 + 2-cycloadditions of a 2-oxa- (g) 3-azabicyclo[2.2.1]hept-5-ene with unsymmetrical alkynes formed cycloadducts. 

Tetrasubstitution of one of the ethylene molecules in the symmetric coplanar arrangement desymmetrizes the pathway of least motion - or highest symmetry - from D2/1 to in which the highest occupied orbital of the reactant pair in Fig. 6.6 correlates no better with that of the tetrasubstituted cyclobutane than do the analogous MOs in Fig. 6.2 ... 

Laurenti, D., SanteUi-Rouvier, C., Repe, G., and SantelH, M., Synthesis of cis, cis, cis-tetrasubstituted cyclobutanes. Trapping of tetrahedral intermediates in intramolecular nucleophihc addition,/. Org. Chem., 65, 6418, 2000. 

The alkylation of enamines with nitroolefins, which gives intermediates for reductive cyclization (6S2), also provided an example of a stable cycliza-tion product derived from attack of the intermediate imonium function by the nitro anion (683). A previously claimed tetrasubstituted enamine, which was obtained from addition of a vinylsulfone to morpholinocyclohexene (314), was shown to be the corresponding cyclobutane (684). Perfluoro-olefins also gave alkylation products with enamines (685). Reactions of enamines with diazodicarboxylate (683,686) have been used diagnostically for 6-substituted cyclohexenamines. In a reaction of 2-penten-4-one with a substituted vinylogous amide, stereochemical direction was seen to depend on solvent polarity (687). 

Pt(II) to the alkyne of the substrate likely triggers all these events. The cycloisomerization might undergo a metallacyclic intermediate that proceeds to eliminate /3-H. The formation of cyclopropanes is presumably succeeded via alkenyl platinum carbene followed by platina(IV)cyclobutane intermediates. The extension using formal metathesis of the enynes includes two transformations, the formation of 1,3-diene moieties and the stereoselective tetrasubstituted aUcene derivatives via O C allyl shift, both leading to diverse structural motifs and serving as the key step in the total synthesis of bioactive targets (Scheme 83). 

Syntheses of Alkylidene Cyclopropanes and Cyclobutanes by formal Elimination of a Hydroxyl Group and a Heteroatomic Moiety The methods discussed above, although efficient, possess important limitations. They do not permit, for example, the synthesis of tetrasubstituted alkylidene cyclopropanes due to the unavailability of the starting selenides, the alkylation of a-selenocyclopropyllithiums with sec-alkylhalides being not feasible at present. 

Treatment of diester 10 with diethyl oxalate in the presence of base gave the disodium salt 11, which was thereafter alkylated to afford the tetrasubstituted thiophene 12. This material was subsequently used as a precursor for preparation of 3,4-dimethoxythiophene 9 <04T10671>. In a similar series of reactions involving glyoxal and suitable sulfides, several cyclobutane substituted 2,5-diacylthiophenes were synthesized <04HC26>. 

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