Cyclobutane moieties cycloaddition

High yields of intramolecular (2 + 2)-cycloadducts are obtained from irradiation of (159). The success of the intramolecular additions is reputedly due to the flexibility of the ether linkages. The use of the (2 + 2)-photocycloaddition reactions in the synthesis of so-called paddlanes (160) has been explored. Irradiations of (161) are carried out through a Pyrex filter and are best in cyclohexane as the solvent. The yields of the adducts with two cyclobutane moieties (160) is very good. These products are accompanied by small amounts of the mono-cycloaddition product (162). 

This method in the content of microwave-assisted cycloaddition reactions with relevant dienophiles via electrocyclic ring-opening which facilitates generation of a reactive diene 31 for an inter-molecular Diels-Alder [4 + 2] cycloaddition (Scheme 3.29) has also been demonstrated. The overall scope of this method is broad and amenable to a variety of functional group substitutions on the aromatic as well as the cyclobutane moiety. The reported yields range from modest to excellent and the overall diastereoselectivity is impressive. 

Within the cubane synthesis the initially produced cyclobutadiene moiety (see p. 329) is only stable as an iron(O) complex (M. Avram, 1964 G.F. Emerson, 1965 M.P. Cava, 1967). When this complex is destroyed by oxidation with cerium(lV) in the presence of a dienophilic quinone derivative, the cycloaddition takes place immediately. Irradiation leads to a further cyclobutane ring closure. The cubane synthesis also exemplifies another general approach to cyclobutane derivatives. This starts with cyclopentanone or cyclohexane-dione derivatives which are brominated and treated with strong base. A Favorskii rearrangement then leads to ring contraction (J.C. Barborak, 1966). 

Allene ketene cycloadditions are of greater synthetic utility than cither mixed allene dimerization or mixed ketene dimerization. In this class of reaction the ketene is the more reactive species and homodimerization of ketene can be minimized by use of excess allene. Such cycloadditions always result in 2-alkylidenecyclobutanones with the sp carbons of both moieties forming the initial bond. In substituted allenes and ketenes, mixtures of stereoisomers of 2-alkylidenecyclobutanones are obtained with very little stereoselectivity, the stereoisomers arise from cisUrcins isomerism in the cyclobutane ring and EjZ isomerism of the exocyclic double bond. In unsymmetrically substituted allenes some regiochemical preference for ketene cycloaddition is observed. Examples of dimethylketene allene cycloadditions are summarized in Table 1,2... 

Virtually all reactions involving cyclobutane formation via cycloaddition of a cumulene to another C —C double-bond system involves excitation of this latter moiety, e.g. an enone or a quinone, and not of the allene or ketene itself.1 Earlier examples of such reactions have been discussed in Houben-Weyl, Vol. 4/5 b, pp 926 931. 

Many examples of the intramolecular [2 + 2] photocydoaddition of alkenes to benzene derivatives have been reported. The acetophenone derivative 41 undergoes an efficient [2 + 2] photocydoaddition, leading to the cyclobutane derivative 42 (Scheme 5.9, reaction 18) [46, 47]. It was shown that, in this case, a nn triplet state is involved. The presence of a nitrile group in compound 43 induces a [2 + 2] cycloaddition at position 1,2 of the aromatic moiety, leading to intermediate VIII (reaction 19) [48]. Following tautomerization, the final product 44 is formed. 

Alkyl tethered alcohols such as D-mannitol and L-erythritol [20], have been used to bring cinnamyl units together for photocycloadditions. However, this probably involves cycloaddition between an excited enone moiety and the tethered alkene. Other examples of carbon linked alkenes include perhaps the earliest example of alkene+alkene photocycloaddition. Liu and Hammond [21] reported the formation of cyclobutane from the triplet irradiation of myrcene (see Sch. 11). 

The [2 + 2] cycloaddition represents the most general and direct pathway for the formation of a cyclobutane structure from two alkene moieties, as outlined in Scheme 2.126. This process may occur as a concerted reaction via a cyclic transition state (mechanism a), as a stepwise reaction involving the formation of an acyclic biradical (mechanism b), or through bipolar (mechanism c) intermediates. Depending upon the structure of the reactants, cycloaddition may occur by any of these mechanisms. 

Cyclobutane formation, occasionally in fairly low yield due to ring-opening reactions, also occurred by photochemical [2 - - 2] cycloaddition of vinylcyclopropane derivatives to an a, -unsaturated ketone moiety, " a cyclobuta-1,3-diene, a 1,4-benzoquinone, 2-acylthiophenes, and on irradiation of e t/o,enr/o-2,4-bis[( )-2-(methoxycarbonyl)vinyl]bi-cyclo[1.1.0]butane. A formal [2-1-2] cycloaddition also occurred on reaction of tricyclo[3.1.0.0 ]hex-3-ene with methyl 6-oxo-5-phenyl-l,3,4-oxadiazine-2-carboxylate to give methyl 9-oxo-10-phenyl-8-oxapentacyclo[4.4.0.0 ". 0 .0 °]decane-7-carboxylate, albeit in very low yield, after nitrogen extrusion. ... 

If the [3-h 2]-cycloaddition reaction of a methylenecyclopropane is performed with a remote alkene or alkyne moiety within the same molecule, products 2 of the bicyclo[3.n.0]-type (n < 3) or the bicyclo-[n.3.0]-type (n > 3) can, in principle, be obtained. The former of these product types can be considered as unhkely, as an alkene or alkyne separated by only one or two atoms from the methylenecyclopropane would give rise to a strained annulated ring, i.e. a cyclopropane or a cyclobutane. It is known from investigations of photochemically initiated intramolecular [2 3-2] cycloadditions of alkenes that the minimum size required for a spacer between 7t-systems is three atoms in a reaction of a non-crossed type. There are actually a few examples of photoinduced intramolecular cycloadditions of the crossed type involving substrates with short spacers (n =... 

Various photochemical (2 + 2)-cycloadditions of heteroaromatic compounds have been reported in which an enone moiety is incorporated either into the olefinic reagent or into the heteroaromatic compound. Both furan and thiophene have been found to give cycloaddition reactions with maleic anhydride derivatives in the presence of a sensitizer.202 213 The cycloadducts (185 and 186) were formed in high yield, but in the case of 2,5-dimethylthiophene, cyclobutane formation was the minor pathway, as oxetane formation predominated.210 Cyclic enones, such as 2-cyclopenten-l-one and 2-cyclohexen-l-one reacted with furan to afford mixtures of (2 + 2)-cycloadducts (187a, R = H) and (188),... 

Asymmetric [2+2] cycloaddition reactions of fumarates bearing a chiral moiety with ketene acetals lead to optically active substituted cyclobutane ring systems under Lewis acid catalysis. 

Another interesting photochemical reaction that occurs with the monolayers is dimerization. This is exempUfled by the photochemical behaviour of the SAM of 7-(10-thiodecoxy)coumarin (52) on polycrystaUine gold. Irradiation at 350 nm results in the (2 -f 2)-cycloaddition of the coumarin moieties. The photodimerization is a reversible process by irradiating at 254 nm. Better regioselectivity in the cycloaddition is obtained when the solid monolayer is irradiated rather than when it is in contact with benzene. The dimer formed is the yn-head-to-head dimer identified as 53 . Self-assembled monolayers of cis- and frani-4-cyano-4 -(10-thiodecoxy)stilbene (54) are also photochemically reactive. Irradiation of a thin film in benzene solution using A, > 350 nm results in the formation of a photostationary state with 80% of the cis-isomer present. Irradiation in the solid shows that cis.trans isomerism occurs but that trans.cis-isomerism fails. Prolonged irradiation brings about (2 - - 2)-cycloaddition of the stilbene units to afford cyclobutane adducts. Such dimerization is a well established process . The influence of irradiation at 254 nm or 350 nm of self-assembled monolayers of 10-thiodecyl 2-anthryl ether on polycrystaUine... 

The pyrimidine bases thymine (T) and cytosine (C) form dimers at sites with adjacent pyrimidine moieties, so-called dipyrimidine sites, in the DNA chain, which have been well characterized with respect to chemical structure and mutagenic potential. The dimerization presented in Scheme 8.1 is a [In+ln] cycloaddition (see Section 7.3) involving the two C(5)=C(6) double bonds, leading to cyclobutane structures denoted by the symbol T< >T, or generally Pyr< >Pyr. 

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