Cyclobutanes, preparation cycloaddition reactions

Diazafluorenes such as 129 have found use as cognition enhancers <1995USP5424430> and biologically active cyclobutane oligodeoxyribonucleotides such as 130 have been prepared using a photochemical cycloaddition reaction <2003W0070741>. 

The preparation of novel, strained tricyclic (3-lactams (Fig. 22) containing a cyclobutane ring has been developed to be performed by intramolecular [2+2] cycloaddition reactions of 2-azetidinone-tethered enallenols [299],... 

By using a stoichiometric amount of the chiral titanium reagent prepared by mixing chiral diol, Titanium IV) Chloride, and titanium tetraisopropoxide, the asymmetric [2 + 2] cycloaddition reaction of 1,4-benzoquinones and styrenes gives the corresponding cyclobutane derivatives with high optical purity. These rearrange to 2,3-dihydrobenzofuran derivatives on mild acid treatment (eq 13). ... 

Photochemical [2+2] cycloaddition reactions and [2+2] cycloaddition reactions of ketenes have been widely used for the preparation of cyclobutane derivatives. The thermal [2+2] cycloaddition reaction is known to proceed between highly electrophilic and nucleophilic alkenes alkenes having cyano, fluoro, and trif-luoromethyl groups react with electron-rich alkenes such as alkenyl ethers and sulfides [8]. As for the catalyst-mediated [2+2] cycloaddition reactions, Lewis acids are known to promote [2+2] cycloadditions [9,10,11,12,13,14,15,16,17,... 

The first catalytic asymmetric [2+2] cycloaddition reaction was reported in 1989 by the use of the chiral titanium reagent prepared from the tartrate-derived chiral 1,4-diol 1 and TiCl2(0-z-Pr)2 [26]. Treatment of methyl ( )-4-oxo-4-(2-oxo-l,3-oxazolidin-3-yl)-2-butenoate (2a) and l,l-bis(methylthio)ethylene (3a) with a 10 mol % amount of the chiral titanium reagent in a mixed-solvent of toluene and petroleum ether (RE.) at 0 °C afforded the cyclobutane derivative 4a in 96% yield in nearly optically pure form (98% ee) (Scheme 1). In this section we... 

The chiral titanium catalyst prepared by mixing the diol 1, TiCl4, and Ti(0-i-Pr)4 in a 1 1 1 ratio promotes the asymmetric [2+2] cycloaddition reaction between styrenes 16 and 1,4-benzoquinones 17 to afford cyclobutane derivatives in good optical purity (Scheme 10 and Table 5) [37]. This reaction is not a truly catalytic reaction because excess amounts of the catalyst (5 molar amounts) have to be employed in order to obtain a high enantiomeric excess. The catalyst in this reaction is thought to be different from the one prepared from the diol 1 and TiCl2(0-i-Pr)2 in a 1 1 ratio as described previously. 

Highly enantiomerically enriched cyclobutane derivatives are prepared via dias-tereoselective [2+2] cycloaddition reactions of chiral ethylene derivatives for instance, by photochemical (Scheme 11 and Scheme 12) [38, 39] and thermal [2+2] cycloaddition (Scheme 13) [40,41] reactions of chiral alkenes and by the [2+2] cycloaddition of chiral keteneiminium ions (Scheme 14) [42]. 

The photolytic ring closure of stilbene type compounds has been widely employed as a versatile method in the preparation of condensed aromatic and heteroaromatic compounds [67]. According to orbital symmetry conservation rules [68], the reaction is a reversible conrotatory [ 6] electrocyclization of the czs-isomer (e.g. czs-stilbene (1), Scheme 12) to the trans-4 a,4 -dihydrophenan-threne (lb). Because the cist trans-isomerization of stilbenes is sufficiently fast under the reaction conditions applied, the trans-isomer of the stilbenes can also be used. Depending on concentration, structure, and solvent, the stilbene type compounds can also undergo a [2 + 2] cycloaddition reaction leading to aryl-substituted cyclobutanes [69]. 

The fused cyclobutane derivatives produced via the above cycloaddition reactions have been utilized as synthetic precursors for the preparation of indole-2-acetonitriles (Scheme 6) [23]. First, the acetyl-substituted cyclobutanes 28 were converted to the cyclobutanone derivatives 29, which were in turn treated with hydroxylamine to provide the corresponding oximes. Beckmann fission of oximes 30 in the presence of thionyl chloride then produced the l-benzoylindole-2-aceto-nitrile derivatives 31 in good yield. 

A particularly good route to four-membered rings is via a (2-i-2]-cycloaddition. With a suitably functionalized precursor, this is a good method for preparing amino-cyclobutane amino acids. Reaction of enamine 7319 (derived from isobutyraldehyde)... 

Variations on the theme of [2 + 2]cycloaddition reactions as a route to cyclobutanes continue to be developed. 1,2-Diynylcyclobutanes (29) can be prepared by triplet-sensitized photochemical dimerization of the corresponding enynes in general, this method cannot be used for the efficient synthesis of more highly substituted cyclobutanes. Similar photochemical methods have also been used to prepare a range of substituted ci5-l,2-diaminocyclobutanes (30), and the tricyclic compounds (31), which can serve as precursors to the tricyclo[4.2.0.0 ]octanes (32) via the Wolff rearrangement. ... 

Cycloaddition Reactions.—These form the largest class of useful organic photochemical synthetic methods. The formation of cyclobutanes, with or without further rearrangement, dominates the subject, but larger rings have also been prepared. 

The catalytic [2-1-2] cycloaddition reactions are an essential and important tool for the syntheses of cyclobutane derivatives. In particular, the catalytic cycloaddition reactions of silyl enol ethers, which are the most easily prepared ketone equivalents, have been an attractive method for cyclobutane syntheses. A number of catalytic methods that give high stereoselectivities and yields have been developed. Recently, several studies on the synthetic utilization of the [2-1-2] cycloaddition have been reported [43]. Further improvements are required for more practical and large scale syntheses. We look forward to further developments of the [2-1-2] cycloaddition reaction with silyl enol ethers in the near future. 

From a preparative point of view, the photochemical [2 + 2] cycloaddition is the most important of the photochemical reactions especially the cycloaddition involving enones. The [2 + 2] cycloaddition is the method of choice for the construction of cyclobutane derivatives as well as cyclobutane units within larger target molecules. 

One recent example of preferential [2+2] cycloaddition of dienes is the reaction of 2-siloxybutadienes with allenecarboxylates to afford cyclobutanes used for the preparation of very hindered cyclohexene systems [22]. 

Reactions of Cjq with metal carbene complexes also yield the [6,6] methano-fullerenes [392]. These adducts are probably not formed via a carbene addition, but via a formal [2-1-2] cycloaddition under formation of a metalla cyclobutane intermediate. The Fischer carbene complex [mefhyl(methoxymethylene)]pentacarbonyl chromium can be utilized to prepare l,2-mefhyl(methoxymethano)-fullerene in 20% yield [392]. A tungsten carbene complex was primarily used to initiate the formation of a polyacetylene polymer, but it was discovered that addition of to the complex-polymer-mixture improves the polymerization and dramatically increases the catalytic activity of the carbene complex [393]. can be integrated into the polymer via carbene addition. 

Cyclobutanes can be conveniently prepared from cyclobutene derivatives through electrophilic addition, catalytic hydrogenation, nucleophilic addition, cycloaddition as well as light-induced addition reactions. 

A special case of the preparation of cyclobutanes from 1,5-dienes via valence isomerization is the use of acyclic or cyclic 1,5,7-trienes which give four-membered rings via an intramolecular [7t + 7ts2] cycloaddition (Diels-Alder reaction). This variant is illustrated for monocyclic tricnes 18 and 20 where two 71-bonds are transformed into a-bonds, resulting in tricyclic compounds 1968 and 21.09... 

In addition to the alkylations discussed above, some special reactions have been reported that enable the solid-phase synthesis of cycloalkanes. These include the intramolecular ene reaction and the cyclopropanation of alkenes (Figure 5.5 see also [44]). Cyclobutanes have been prepared by the reaction of polystyrene-bound carbanions with epichlorohydrin, and by [2 + 2] cycloadditions of ketenes to resin-bound alkenes. 

Narasaka s chiral titanium catalyst, prepared from (Pr 0)2TiCl2 and a tartrate-derived (2R,3R)-l,l,4,4-tetraphenyl-2,3-0-(l-phenylethylidene)-l,2,3,4-butanetetrol, is utilized for the asymmetric [2+2] cycloaddition of A-acyl oxazolidinones to 1,2-propadienyl sulfides possessing a-substituents, which afford methylenecyclobutane derivatives with high enantiomeric purity. These chiral adducts are readily transformed to seven- and eight-membered carbocycles with chiral side chains by the ring-cleavage reaction and subsequent cationic cyclization of the chiral cyclobutane derivative [68] (Eq. 8A.44). 

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