Bicyclic cyclobutenes

Alkenes act as nucleophiles with alkynes in the presence of gold catalysts. In the most simple version of the reaction, enynes are converted with gold complexes or salts, and in the absence of nucleophiles, into rearranged dienes, cyclopropanated carbocycles, and/or bicyclic cyclobutenes. Depending on the length of the tether and the nature of the substituents, the olefin attack to the alkyne occurs in an endo or an exo fashion (equation 33). Besides, substitution at the alkene plays an important role on the regioselectivity of the nucleophilic attack. ... 

The intermolecular version of this reaction results in the formation of complex systems with fewer rings. The group of Snapper has used this reaction in a number of routes to obtain complex natural products. Many of these processes involve the opening of cyclobutenes, and the bicyclic cyclobutenes (Eq. 6.30) provide excellent control of stereochemistry, with the products being highly strained so that they will undergo further thermal reactions [49]. 

One typical example is given by G. Kaupp with the [2+2] cycloaddition of diphenyl-acetylene to 1,4-dioxene leading to a bicyclic cyclobutene in good yield (cf. iv of this chapter). Another example is presented by T. Miyashi starting from naphthoquinonor-bomadiene. In an intramolecular reaction a quadricyclane derivative is quantitatively formed upon irradiation at X > 400 nm. It is assumed that this process involves the diketo-norbomadiene in its triplet state. Although the spin multiplicity of intermediates have not... 

Simple cyclobutanes do not readily undergo such reactions, but cyclobutenes do. Ben-zocyclobutene derivatives tend to open to give extremely reactive dienes, namely ortho-c]uin(xlimethanes (examples of syntheses see on p. 280, 281, and 297). Benzocyclobutenes and related compounds are obtained by high-temperature elimination reactions of bicyclic benzene derivatives such as 3-isochromanone (C.W. Spangler, 1973, 1976, 1977), or more conveniently in the laboratory, by Diels-Alder reactions (R.P. Thummel, 1974) or by cycliza-tions of silylated acetylenes with 1,5-hexadiynes in the presence of (cyclopentadienyl)dicarbo-nylcobalt (W.G, Aalbersberg, 1975 R.P. Thummel, 1980). 

Cyclic dienes and polyenes, monocyclic as well as bicyclic, can be metathesized in the same way as cyclic monoenes. As expected, cyclobutene 27), 1,5-cyclooctadiene, and 1,5,9-cyclododecatriene 28) yield the same polyalkenamer, in this case polybutenamer (1,4-polybutadiene), since these reactants consist of the same base units, i.e.—(CH2)2CH==CH— ... 

A number of the bicyclic ozonides 12 were prepared in good yield (45-65 %) by diimide reduction of furan singlet oxygenates (Eq. 9) 23>. Again, low temperature were essential because the furan endoperoxides readily transform into 1,2-diacyl-ethylenes. Of course, the bicyclic ozonides 12 can alternatively be prepared via ozonolysis of the appropriate 1,2-disubstituted cyclobutene 24). 

The spiroketone 28 was converted into its tosylhydrazone whose sodium salt 29 was heated without solvent in a high vacuum. The bicyclic olefin 30 was formed and being a cyclobutene, Woodward and Hoffmann allowed it to ring-open to afford 31 and these two products were collected in a trap cooled by liquid nitrogen. When the mixture was permitted to warm up, an exothermic reaction (again allowed by W H) set in and the cyclobuteno[4.2.2]propellane 32 was formed11. ... 

The cyclobutene (310) opened at 100 °C to facilitate the intramolecular Diels-Alder reaction, from which the m-fused bicyclic compound (311) was isolated 108). 

The double )5-scission pathway becomes dominant in bicyclic systems (Equations (7)-(9) and Scheme 13). Thus, cyclopentene ozonide (69) gives cyclopropane (Equation (7)) <68TL329l>. Photolysis of the ozonide derived from 1,4-benzodioxins (70) provides a method for the preparation of labile o-benzoquinones (71) (Scheme 13) <87JOC56l6>. Photolysis can also provide a route to unstable compounds and transient species such as the aziridine-2,3-dione (72) (Equation (8)), identified at 77 K using infrared spectroscopy <80JA6902>. Relatively unstable azacarbapenems (73) have been prepared by photolysis of tricyclic compounds containing a cyclobutene ozonide (Equation (9)). On silica, the 1,2,4-trithiolane (74) underwent photo-equilibration (Equation (10)) with the 1,3-dithetane (75) and sulfur. 

For example, acetolysis of r/n /-6-tosyloxytricyclo[5.2.0.02 5]nona-3.8-diene proceeded smoothly at 35 C with stereospeeific rearrangement to c.Y0..mj-9-acetoxylricyclo[4.2.1,02 5]nona-3,7-diene (l).30 Interestingly, the rate of acetolysis of the substrate was considerably enhanced kre[25 C = 6.8 x 104) as compared with that of its bicyclic counterpart 2.30 An important conclusion from these studies is that the anchinteric assistances by cyclobutene in the form of homoallylic participation is effective in the stabilization of the carbocation intermediate. It was found in another study that cyclobutene is better than cyclobutane in terms of anchimeric assistance.31... 

Ring closure to a bicyclic product could also be expected in the irradiation of peril uoroazacyclohexadiene 25, but the product obtained, in 87% yield, is peril uoro[l-isopropyl-3-(methylimino)cyclobutene] (27), which is presumed to be formed via ring opening to azatriene 26, followed by electrocyclic ring closure to the cyclobutene and a 1,3-fluorine shift.20... 

Formula 366) gives a bicyclic enol ether (Formula 367) which is hydrolyzed to Formula 368 (161,162). The sequence of Formulas 366-368 represents a potentially general synthesis of bicyclic cyclobutanone derivatives. A clever synthesis of m-3-cyclobutene-l,2-dicarboxylic acid anhydride (Formula 369) has been accomplished by irradiation of muconic anhydride (Formula 370) in ether (163). 

Similarly, thermolysis of naphthacene photooxide (329) leads to naphtha-cenequinone (330), the bicyclic acetal 331, and the cyclobutene diether 332.178 These products are shown to have been formed by the involvement of the meso-diepoxide 333 by means of trapping experiments. 

An important and frequently observed phenomenon in alkene pyrolysis is the ready equilibration of E and Z isomers at FVP temperatures above 500 °C. The apparently contrathermodynamic conversion of the E into the Z isomer has been quantified over the range 500-900 °C for stilbene, cinnamyl alcohol and cinnamonitrile37. In the last case, the proportion of Z isomer increases to 38% at 900 °C. In certain cases the diradical implicit in the isomerization process can be trapped by an intramolecular reaction and this is exemplified by the formation of 2-phenylindane in low yield from FVP of 56 at 700 °C37. The cis cyclobutene diester 58 is assumed to be formed as an intermediate in the FVP of the bicyclic sulphone 57 at 775 °C by loss of SO2 and ethylene. Under these conditions, however, it reacts further to give equal proportions of the E diesters 59... 

The action of A-chlorosuccinimide, or a source of positive fluorine such as Selectfluor , in aqueous acetonitrile on the alkene 138 (R1 = Me) is to open the azetidine ring by attack at the allylic position to yield the cyclobuten-3-ol 139 (R OH, R2 = H, R3 = Me) <2003JOC5292>. Chlorosulfonyl isocyanate (CSI) reacts with 138 (R = Et) to give both a chlorobutene 139 (R1 = Cl R2 = CONH2 R3 = Et) and the bicyclic reduced pyrimidone 140 (R1 = Et). However, the action of CSI on the more substituted 2-azabicyclo[2.2.0]hex-5-ene 141 provided the reduced mono-cyclic pyrimidone 142 <2003JOC1626>. 

Enynals 104 can undergo a palladium-catalyzed cyclization to form the pyrylium intermediate 105, which upon deprotonation affords the triene 106. In the presence of DM AD, a [2+2]-cycloaddition then occurs to form the tricyclic 4//-pyran intermediate 107, which undergoes expansion of the cyclobutene ring to afford the bicyclic 4//-pyrans 108 (Scheme 34) <2004S1409>. 

Conversely, the photoinduced ring-opening of cyclobutenes allows the construction of medium-sized hetero- or carbocycles, starting from bicyclic frameworks. Alkenes can undergo thermal (metal-assisted) or photochemical [2 + 2]-cycloaddition to a variety of alkynes the subsequent two-carbon ring-enlargement can serve as a versatile method for the preparation of hydroazulenes and dioxacyclooctadiene derivatives (Scheme 9.44) [74, 75]. 

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