CuOTf-catalyzed photocycloaddition

Oxabicyclo[3.2.0]heptanes are also produced in the CuOTf-catalyzed photocycloadditions of allyl 2,4-hexadienyl ethers (eq 24). The CuOTf-catalyzed photocycloadditions of bis-2,4-hexadienyl ethers are more complex. Thus UV irradiation of 5,5 -oxybis[( )-l,3-pentadiene] in THF for 120 h produces vinylcy-clohexene and tricyclo[3.3.0.0 ]octane derivatives (eq 25). However, shorter irradiations reveal that these products arise by secondary CuOTf-catalyzed rearrangements of 6,7-divinyl-3-oxabicyclo[3.2.0]heptanes that are the primary photoproducts (eq 26). UV irradiation of the divinylcyclobutane intermediates in the presence of CuOTf promotes formal [1,3]- and [3,3]-sigmatropic rearrangements to produce a vinylcyclohexene and a 1,5-cyclooctadiene that is the immediate precursor of the tricyclo[3.3.0.0 ]octane. 

Stereoselective copper(l)-catalyzed [2 -I- 2]-photocycloaddition of 1,6-heptadienols has been used as a key step in the synthesis of several natural products. The total synthesis of the sesquiterpenes a-panasinsene 47 and P-panasinsene 48 has been achieved by CuOTf catalyzed photocycloaddition of the dienol 43 as the key step (Scheme 15). The resulting bicyclo[3.2.0]heptanol 44 was then converted to the natural products through the ketone 46. It is noteworthy that direct access to the requisite intermediate 46 involving photoaddition of isobutylene to the enone 45 failed, illustrating the importance of the copper(l)-catalyzed photocycloaddition of 1,6-heptadienols. 

CuOTf-catalyzed photocycloaddition of the tetraene 96 produces a mixture of the compounds 98,99, and 100 (Scheme 25). The 1,2-divinyl cyclobutanes 97 initially formed from [2 + 2]-addition of the tetraene 96 undergo further reaction on prolonged irradiation in the presence of CuOTf to form these products. The tricyclic compound 100 arises from intramolecular 2jt + 2Jt addition of cyclooctadiene derivative 99. In fact, the transformation of cis,c/s-l,5-cyclooctadiene 101 to the tricychc compound 102 on irradiation in the presence of CuCl was the first example of an intramolecular Cu(I)-catalyzed photocycloaddition reaction. ... 

Employing this protocol, spirocyclopentanones can be obtained when cyclic ketones are used, as illustrated in Scheme 31.The spirocyclopentanone 129, obtained from 4-methylcyclohexanone 126, has been converted to the spiro ketone 130, which was earlier transformed to the sesquiterpene a-cedrene 131 (Scheme 31). Thus, CuOTf catalyzed photocycloaddition of 1,6-heptadienes provides a novel route to spiro cyclopentanones, also. 

Due to its versatile applicability, the CuOTf-catalyzed [2 + 2] photocycloaddition was used successfully to study the topology of the intermolecular and intramolecular dimerization of norbomene derivates. When a racemic mixture of compound 27 is transformed in the presence of CuOTf, a 1 1 mixture of two stereoisomers (28a,b) is... 

Scheme 5.5 Intramolecular CuOTf-catalyzed [2 + 2] photocycloaddition, and its application to organic synthesis.

Copper(I) catalysis is very well established to promote intramolecular [2+2] photocycloaddition reactions of l,n-dienes (review [351]). The methodology recently enjoyed a number of applications [352-354], It is assumed that CuOTf, which is commonly applied as the catalyst, coordinates the diene and in this way mediates a preorganization. The Ghosh group recently reported a number of CuOTf-catalyzed photochemical [2+2] cycloaddition reactions, in which an organocopper radical complex was proposed as a cyclization intermediate (which should, however, have a formal Cu(II) oxidation state) (selected references [355-357]). A radical complex must, however, not be invoked, since the process may either proceed by a [2+2] photocycloaddition in the coordination sphere of copper without changing the oxidation state or according to a cycloisomerization/reductive elimination process. 

That CuOTf-catalyzed 2n + 2n photocycloadditions are not restricted to cyclic alkenes was first demonstrated in mixed cycloadditions involving allyl alcohol. To suppress homodimerization of e/jcto-dicyclopentadiene (i.e. eq 11) the diene to Cu ratio is maintained at < 1 1 and allyl alcohol is used as solvent. Under these conditions, a high yield of mixed cycloadduct is generated (eq 19). ... 

That both C=C bonds participating in 2n + 2n photocycloadditions can be acyclic is evident from the photobicyclization reactions of simple diallyl ethers that deliver bicyclic tetrahydrofurans (eq 20). In conjunction with ruthenium(IV) oxide-catalyzed oxidation by sodium periodate, these CuOTf-catalyzed photo-bicyclizations provide a synthetic route to butyrolactones from diallyl ethers (eq 20), The synthetic method is applicable to the construction of multicyclic tetrahydrofurans and butyrolactones from diallyl ethers (eq 21 and eq 22) as well as from homoallyl vinyl ethers (eq 23). ... 

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). ... 

Ghosh et aP have recently demonstrated that the CuOTf-catalyzed [2 -H 2]-photocycloaddition can be successfully carried out when 1,6-heptadienes are incorporated in a carbohydrate derivative, thus widening the scope of the Cu(I)-catalyzed photocycloaddition. The diene 67a, on irradiation in the presence of CuOTf, afforded the thermodynamically less stable cis-syn-cis adduct 68a (Scheme 20). Initially, this unexpected stereochemical outcome was thought to arise through the tri-coordinated Cu(I) complex 69. However, photocycloaddition of the analogous diene 67b (with benzophenone as sensitizer) in the absence of a Cu(I) catalyst also produced the cis-syn-cis adduct 68b, excluding the possibihty of the involvement of the Cu(I)-complex 69. Possibly, the observed stereoselectivity arises through the Cu(I)-... 

Copper(I)-catalyzed intramolecular [2 + 2]-photocycloaddition of diallyl ethers and homoallyl vinyl ethers provides a new route to 3-oxabicyclo- and 2-oxabicyclo[3.2.0]heptanes, respectively.Different structural variants of diallyl ethers have been investigated. UV irradiation of diaUyl ethers 77a-f in the presence of CuOTf catalyst produces 3-oxabicyclo[3.2.0]heptanes 78a-f in moderate to excellent yields (Scheme 22). The diallyl ethers 77c and 77d having alkyl substitution at the aUyhc position produce exclusively the 2-exo-alkyl-3-oxabicyclo [3.2.0] heptanes 78c and 78d, respectively. The observed stereoselectivity arises through photocycloaddition of the Cu(l)-diene complex 80, which is stericaUy less crowded than the complex 81 with an axial alkyl group. The bicychc ethers 78 can be oxidized smoothly to the lactones 79 with RuO. Cu(l)-catalyzed photocycloaddition of homoallyl vinyl ethers 82 also proceeds smoothly, producing 2-oxabicyclo[3.2.0]heptanes 83 (Scheme 22). 

Scheme 5.4 Intramolecular [2 + 2] photocycloaddition of 3-hydroxy-l,6-heptadiene derivatives catalyzed by CuOTf.

Mattay et al. employed asymmetric copper(I)-catalyzed intramolecular [2 + 2]-photocycloaddition reactions in a synthetic approach to (+)- and (— )-grandisol [56]. Racemic dienol 33 was irradiated in the presence of CuOTf and a chiral ligand to yield mainly cyclobutanes 34 and ent-34 as a mixture of enantiomers. Other 1,6-dienes were also employed. A number of chiral nitrogen-containing bidentate ligands were tested, the most effective of which, (4S,4 S)-4,4 -diisopropyl-2,2 -bisoxazoline (35) and (4R,47 )-4,4 -diethyl-2,2 -bisoxazoline (36), ensured a minor enantiomeric excess of <5% ee (Scheme 12). The coordination of the diene to the chiral Cu(I) complex under formation of a complex of type 37 was proved by CD analysis. The authors suggest a lower reactivity of the chiral complex compared to the copper ion coordinated to solvent molecules as the reason for the low enantioselectivities observed. 

An isolable CuOTf complex of a highly strained alkene, trans-cycloheptene, is produced by UV irradiation of a hexane solution of cis-cycloheptene in the presence of CuOTf (eq 14).i Photocycloaddition of cycloheptene is also catalyzed by CuOTf. Surprisingly, the major product is not a trans,anti,trans dimer analogous to that formed from cyclohexene (eq 12) but rather a trans,anti,trans,anti,trans trimer (eq 15). ... 

It is now well established that Cu(l)-catalyzed [2 + 2]-photocycloaddition of alkenes requires formation of a complex in which one copper is coordinatively linked with two alkene units. Among the various copper salts (CuCl, CuBr, CuOTf) used, the triflate anion in CuOTf has exceptional weak coordinating ability compared to halide ions, which compete with alkene for coordination with copper. Thus, CuOTf exhibits a strong tendency to form 1 2 Cu-alkene complexes compared to CuCl or CuBr. This is reflected in improved yields of adducts obtained with CuOTf rather than CuCl or CuBr (vide infra). In addition, CuOTf is soluble in most organic solvents and is stable under the photochemical reaction conditions. Hence, CuOTf is the catalyst of choice for [2 + 2]-photocycloaddition between two nonconjugated alkenes. 

Copper(I)-catalyzed intermolecular photocycloaddition requires that one of the reacting alkenes must be highly strained and reactive. It was already stated that norbornene 3 undergoes intermolecular addition to form the dimer 4 (Scheme 2) in 38% yield with CuBr and in 88% yield with CuOTf as the catalyst. This is the first example of copper(I)-catalyzed intermolecular (2 -t 2]-photocycloaddition." Similarly, endo-dicyclopentadiene 5, on irradiation in the presence of CuOTf, undergoes (2 + 2]-addition at the more stained 8,9-double bond to form the dimer 6 (Scheme 3). Cyclopentene does not undergo dimerization with CuBr, while with CuOTf it forms the dimers 11 (30%) and 12 (2%) (Scheme 5). ... 

Irradiation of cyclohexene in the presence of CuOTf produces the dimers 14 (49%) and 15 (8%), along with the cyclohexylcyclohexene 16 (24%) (Scheme 5)T The stereochemical outcome in Cu(I)-catalyzed dimerization of cyclohexene may be the result of cis-tram isomerization on irradiation of the initially formed Cu(I)-cyclohexene complex to the trans-cyclohexene-CuOTf complex 13, followed by a concerted ground state 2 + 2 cycloaddition of the highly strained tram-cyclohexene to another cyclohexene. Cycloheptene, on the other hand, produces the aU tra s-fused trimer 17 (Scheme 6) as the sole product. A 1 3 CuOTf-trans-cycloheptene complex has been proposed to be the precursor of this product. No dimerization reaction has been observed for cyclooctene and acychc olefins.However, mixed photocycloaddition occurs with cyclooctene if the other olefin is sufficiently reactive. Thus, cyclooctene adds to norbornene to produce the cyclobutane derivative 18 in 40% yield. GDdimerization was also observed when a mixture of cyclohexene and cycloheptene was irradiated in the presence of CuOTf to yield the adduct 19 (Scheme 6). ... 

Copper (I)-catalyzed intramolecular photocycloaddition between two acycHc double bonds was first observed by Evers and Mackor in 1978. They demonstrated that although 3-oxabicyclo[3.2.0]heptane 26 is formed from diallyl ether 25 (Scheme 8), 4-hydroxy-1,6-heptadiene 27 produces an endo,exo (3 2) mixture of 3-hydroxy bicyclo[3.2.0]heptanes 28 (Scheme 9) on irradiation in presence of CuOTf. The generahty and scope of this reaction were investigated in great detail by Salomon et al. The acyclic dienes... 

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