Tricyclic intramolecular photocycloaddition

The photoreactions of mono- and di-cyanonaphthalene derivatives with al-lyltrimethylsilane have been reported by Mizuno and Albini, independently [136,428,433,436], The product ratios of photocycloadducts via exciplexes and the allylated products via electron transfer were dependent on the solvent polarity and additives. The intramolecular photocycloaddition of the reductive allylated products efficiently gives tricyclic compounds in high yields [428,433,436] (Scheme 23). 

Hoffman and Pete suggested the presence of acid can increase both chemos-electivity and efficiency, and the role of acids was investigated in detail. For example, irradiation of O-alk-3-enylsalycylates (212) at 254 nm yields tricyclic compounds (213) through 214-216 [267] (Scheme 62). The efficiency of the intramolecular photocycloaddition increased and the reaction mixture was greatly simplified when the reaction was carried out in methanol in the presence of a catalytic amount of acid. Irradiation of 3-alkenyloxyphenols (217) in a methanolic solution yields benzocyclobutenes (218 and 219) [268-270], The efficiency increases if the reaction was carried out in the presence of H2S04. 

A number of model esters related to lac resin have been prepared. These esters have the basic cedrane skeleton (149) or the C-2 epimeric structure. In an approach to the synthesis of cedrene (152), the intramolecular photocycloaddition of the dienone (150) was carried out at low temperature. A major tricyclic compound (151) was obtained and its structure was verified by X-ray analysis of its anisylidene derivative. Further work is required to bring about the rearrangement of a derivative of (151) to give cedrene. Further details on the hydroxylation (with O3) and chlorination (with PhICl2) of cedrol, patchoulol, and their derivatives have been presented. The results of this study are in keeping with those obtained previously. 

The tricyclic ketone (17), a fragrant and volatile key compound of the zizaene (19) synthesis, results from a fragmentation of the tetracyclic mesylate (16). This skeleton has also bron formed by intramolecular photocycloaddition of the easily accessible enol acetate (18). Obviously, the ting strain of (16) is a strong driving force (Scheme 10). 

Functionalized substituted cyclopentanes and spirocyclopentanes were easily accessed by intramolecular photocycloaddition of dihydrofuran based dienes catalyzed by Cu(i) salts. Thus, tricyclic compound 39 was synthesized in 60% yield starting from 38 (Scheme 2.22). Notably, 39 can be easily transformed upon treatment with triflic acid into substituted cyclopentanones, which are important building blocks in the total synthesis of natural products. ... 

The photocycloadditions of 2,3-dimethyl-l,3-diene with 4-(alk-l-ynyl)-substituted coumarins (5) produced a mixture of 4 + 2- and 4 + 4-cycloadducts (6) and (7), respectively. However, the corresponding thiocoumarins (8) yielded a single 4 + 2-cycloadduct (9) (Scheme 2)." The intramolecular photocycloadditions (>290nm) of 1,3-enynes with 2-pyridone yielded 2 + 2- and 4 + 4-cycloadducts. The Rh(I)-catalysed formal 5+l-/2 + 2 + 2-cycloaddition of 1-yne-vinylcyclopropanes (10) with two carbon monoxide units produced multifunctional angular tricyclic 5/5/6 compounds (11) in a one-step mechanism (Scheme 3). ... 

The intramolecular photocycloadditions of butenolides with a 2,3-butadienyl substituent at the 5-position (16) produced tricyclic cycloadducts (17) with a methylenecyclobutane moiety as the core unit. The key reaction is the regioselective crossed 2- -2-cycloaddition of the internal allene double bond (Scheme 5). The ruthenium-catalysed 2- -2-intramolecular cycloaddition of allenes and alkynes (18) yielded bicyclo[3.2.0]heptane cycloadducts (19) under mild conditions and with a high diastereo-selectivity (Scheme 6). ... 

Intramolecular photocycloaddition of 6-alkenyl-3-phenylcyclohex-2-en-l-ones affords tricyclic parallel or crossed [2 + 2] products (38) (39) in addition, the 6-propenyl compound gives a bicyclic enone... 

The C-4 substituted tetronates 159 also undergo intramolecular photocycloaddition to give the tricyclic adducts 160 with the heterocyclic ring directly anellated to the cyclobutane moiety. In consistency with the rule of fives, these photocycloadditions proceed exclusively to furnish the straight adducts. 

The skeleton of 47 is a heterocyclic tricyclo[6.2.0.0 ]decane and the similarity to the tricyclic kelsoene is obvious. In the course of the above-mentioned studies we had become curious whether the high facial diastereocontrol in the photocycloaddition reaction could be extended to other bridged 1,6-hexadienes. Kelsoene was an ideal test case. The retrosynthetic strategy for kelsoene along an intramolecular [2+2]-photocycloaddition pathway appeared straightforward. To avoid chemoselectivity problems the precursor to kelsoene should not contain additional double bonds. Alcohol 48, the hydroxy group of which was possibly to be protected, seemed to be a suitable substrate for the photocycloaddition (Scheme 14). Access to the 1,2,3-substi-... 

Intramolecular [2 + 2] photocycloadditions of 3-alkenylcyclopent-2-enones represent the key step in the total synthesis of various natural products, e.g. pentalenolactone 6-methyl ester19 and pentalenic acid,20 as well as in the preparation of strained fenestranes21 and laurenene.22 Similarly, the photoisomerization of 3-alkenylcyclohexcnoncs to tricyclo[6.3.0.01-6]undecanones are steps in the syntheses of tricyclic sesquiterpene isocomene23 and precursors to members of the acorane family.24... 

Synthetic applications of these photocycloadditions to aromatic compounds are sometimes hampered by low chemical yields and poor selectivity in the photoreactions. However, a number of elegant syntheses of tricyclic sesquiterpenes have been hased on intramolecular 1,3-phutocycloadditions ie.g. 3. SI), and these represent a completely new approach to the preparation of such systems. 

In the last 15 years, Wagner and his co-workers have developed the intramolecular ortho photocycloaddition of alkenes to the benzene ring of the acetophenone chromophore. In these photoreactions, the ring opening products of ortho photocycloadducts, 1,3,5-cyclooctatriene derivatives (220), and their secondary photocycloadducts, tricyclic compounds (221), were often produced [271,272] (Scheme 63). The triplet exciplexes generated from ir, ir -triplet states of acetophenone derivatives were postulated as the reactive intermediates [273],... 

The dimerization of thioformylketene was investigated by B3LYP and G3MP2B3 methods. The 4 + 4-pathway has the lowest energy barrier and calculations suggest that the reaction is pseudopericyclic.231 The stereospecific intramolecular 4 + 4-cycloaddition reaction between cyclohexadiene iron tricarbonyl complex and appended dienes (198) generates cyclooctadiene tricyclic adducts (199) (Scheme 56).232 The first example of an asymmetric intermolecular 4 + 4-photocycloaddition reaction in solution between 9-cyanoanthracene and chiral 2-methoxy-l-naphthamides has been reported. The frozen chirality is effectively transferred to the optically active product.233... 

Scheme 5.11 Synthesis of tricyclic cyclo butene derivatives with intramolecular [2 + 2] photocycloadditions of aromatic compounds. The addition is followed by rearrangements leading to the final products.

Bach, T. (2002) Stereoselective total synthesis of the tricyclic sesquiterpene (i)-kelsoene by an intramolecular Cu(I)-catalyzed [2 + 2]-photocycloaddition reaction. Synlett, 1305-1307. 

A few specific examples of cyclopropanation using the above methods are shown in Scheme 2.134. The naturally occurring insecticide /ra -chrisanthemic acid 396 served as an obvious target to check the viability of carbene addition as a preparative method. This compound was first synthesized (in the mixture with the cis isomer) by the monocyclopropanation of 2,5-dimethyl-2,4-hexadiene. Since then, numerous analogs of 396 were prepared by similar reactions. Some of the analogs are now widely used as efficient and ecologically safe pesticides. The formation of the tricyclic hydrocarbon 397 from 1,5-hexadiene proceeds as a sequence of inter- and intramolecular carbene transfer reactions. An initial carbene precursor, CHBr3, is actually employed here as an equivalent of a unique tetradentate Ci synthon The preparation of 398 via intramolecular [2 + 1] photocycloaddition is a typical example of the efficiency of this route for the construction of the polycyclic framework frequently encountered in the structures of natural compounds. 

Intramolecular meta photocycloaddition of 2-MeC6H4CH2CMe2CH2CH CH2 provides appropriate tetracyclic precursors from which the key tricyclic framework required for the synthesis of ( )-ceratopicanol can be obtained.This constitutes an example of a typical holosynthon. N-Benzoyl-N-benzylcinnama-mides and related compounds will photocycloadd in the presence of benzil to give 3-azatricyclo[5.2.2.0 ]undeca-8,10-dien-4-ones with high stereoselectivity, and this constitutes the first example of a photochemical [4+2] cycloaddition of an enone to a benzene ring. For example, irradiation of (60 R = H, alkyl, phenyl = H, Me X = H, OMe, Cl, etc.) gives (61 same R, R, X). 

An example of efficient chiral induction in a photoreaction is provided by the irradiation of inclusion compounds of pyridones (11) with the chiral host (10) (Tanaka et al, Chapter 2). This process afforded optically active p-lactams (12) with ee in the range 91-99%. The intramolecular 2 4-2 alkene photocycloaddition of (13) catalysed by Cu(I) afforded the tricyclic compound (14) in 89% yield,... 

Although a number of syntheses of the angular triquinane sesquiterpene isocomene (18) have now been published, the synthesis by Dreiding et al. is interesting since it features the sequential alkynone cyclisations (14)— -(15) and (16)——(17) as the two key 5-ring annulation reactions. In a new synthesis of the related sesquiterpene silphinene (23) intramolecular(2+2] photocycloaddition from (19) is first used to elaborate the tricycle (20), which on brief exposure to iodotrimethylsilane produces (21). Reduction of (21) to (22), and functional group elaboration then completed the... 

The retrosynthetic disconnection of isocomene leads primarily to the intermediate tertiary carbenium ion 1, which may arise from the intermediate carbenium ion 2 by anionotropic 1,2-alkyl shift. The latter turns out to be the protonation product of the tricycle 3 containing an exocyclic CC-double bond which is generated by a WiT-TiG-methylenation of the tricyclic ketone 4. The concept behind this is formation of the cyclobutane ring in 4 by means of an intramolecular [2-l-2]-photocycloaddition of the 1,6-diene 5. The enone substructure in 5 results from hydrolysis of the enolether and dehydration of the tertiary alcohol function in (65)-l-alkoxy-2,4-dimethyl-3-(2-methyl-l-penten-5-yl)cyclohexene 6. The tertiary alcohol 6 emerges from a nucleophilic alkylation of (65)-3-alkoxy-2,6-dimethyl-2-cyclohexen-l-one 7 with metallated 5-halo-2-methyl-l-pentene obtained by GrigNARD reaction or... 

An intramolecular [2-1-2] photocycloaddition reaction was reported as the key step in constructing the tricyclic core 218 of solanoeclepin A, which includes an intricate bicycle[ 2.1.1 jhexanone moiety. Allene butenolide 217 as... 

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). ... 

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