Cyclobutanes, synthesis from photocycloaddition

The fadal diastereoselectivity of intermolecular cyclopentenone [2 + 2]-photocy-cloaddition reactions is predictable if the cyclopentenone or a cyclic alkene reaction partner is chiral. Addition occurs from the more accessible side, and good stereocontrol can be expected if the stereogenic center is located at the a-position to the double bond. In their total synthesis of ( )-kelsoene (11), Piers et al. [22] utilized cyclopentenone 9 in the [2 + 2]-photocycloaddition to ethylene (Scheme 6.5). The cyclobutane 10 was obtained as a single diastereoisomer. In a similar fashion, Mehta et al. have frequently employed the fact that an approach to diquinane-type cis-bicydo [3.3.0]octenones occurs from the more accessible convex face. Applications can be found in the syntheses of (+)-kelsoene [23], (—)-sulcatine G [24], and ( )-merri-lactone A [25]. 

A modified de-Mayo reaction (shown in Scheme 21) also served as a tool in the first synthesis of a saturated taxane framework with a geminal dimethyl group (79,80). Photocycloaddition of cyclohexene (functioning as a ring C model) to a bicyclic 1,3-diketone derivative from 85 is the key step. In the course of the cyclobutane annealing, the C-8 a ring connection is established contrary to C-3,... 

The sequence of intramolecular photocycloaddition-cyclobutane fragmentation has been used by Crimmins in an excellent manner for the synthesis of pentalenenes and the even more sophisticated lauren-l-ene (27). The latter synthesis was accomplished in 27 steps from cyclopentenone U66). One of the key steps is the reductive cleavage of the tetracyclic cyclobutane (167), followed by hydrogenation of the resulting P,7-unsaturated ester to give keto ester (168 Scheme 57). 

The [2+2]photocycloaddition of 5-arylfuran-2,3-diones (496) to trimethylsilyl-oxyethylenes (495) occurs with high regio- and stereoselectivity to efficiently yield polyfunctionalised cyclobutanes (497). ° A convenient four step stereoselective synthesis of ( + )-norasteriscanolide (500) has used the [2+2]photoadduct (499) from 2-cyclopentenone and the trimethylsilyl enol ether (498) to assemble the 5/8 ring system present in many terpenoids. 2-Naphthaldehyde undergoes regio-and stereoselective [2+2]photoadditon to the cyclic ketene silyl acetals (501) to... 

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). 

The importance of asymmetric synthesis in organic technology was emphasized in Chapter 9. It is also possible to introduce chirality through a photochemical reaction by transferring it from a chiral auxiliary attached to the reacting molecule. If a bimolecular photoreaction is involved, the chiral auxiliary may be attached to any one of the reactants. Examples of such asymmetric induction are cyclobutanes, oxetanes, and cyclohexenes by [4 + 2] photocycloaddition (Pfoertner, 1990). 

Asymmetric [2 + 2] Photocycloadditions. Intramolecular copper-catalyzed [2 + 2] photocycloaddition is a useful methodology for the preparation of bicyclic cyclobutanes and recent studies deal with its asymmetric version albeit with variable success. Diastereoselective reactions are achieved under the control of stereogenic centers incorporated in the dienic precursors. Both CuOTf and the more stable and easy to handle Cu(OTf)2 are suitable catalysts in this context. In the latter case, it is assumed that the copper(I) species is generated from Cu(OTf)2 under the photochemical conditions. A noteworthy example is the application of the CuOTf-catalyzed [2 + 2] photocycloaddition in the stereoselective total synthesis of the tricyclic sesquiterpene kel-soene (eq 128). ... 

Photocycloaddition involving functionalized cyclobutenes, followed by thermolysis of the intermediate fused cyclobutane adduct, is a much exploited strategy in the elaboration of fused six-ring terpenoids. Further illustrations of the scope provided by this strategy have emerged this year (Scheme and Vandewalle and his co-workers have given a further illustration of the use of photoadducts from the bis-trimethylsilyl ether (20) in synthesis. 

The aforementioned method, though elegant, cannot be adapted to the synthesis of head-to-tail homodimerization-or heterodimerization-derived cyclobutane lignans, such as piperarborenine B (157) [58a] and D (158) [58b], both of which were isolated from the stems of the creeping shrub Piper arborescens and exhibit in vitro cytotoxicity against P-388, HT-29, and A-549 cancer cell fines (IC5 <4pg/ml) [58b], They are assumed to arise from the head-to-tail heterodimerization of piplartine-type monomers, with cis-trans-cis and trans-trans-trans stereochemistry, respectively. However, a biomimetic [2+2] photocycloaddition fashion is certainly problematic since homodimerization and head-to-head dimerization and E/Z isomerization would... 

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