Allenes photocycloaddition

Irradiation of cyclopent-2-enones in the presence of allenes affords mixtures of 6- and 7-methylenebicyclo[3.2.0]heptan-2-ones, the latter regioisomers being formed preferentially.4,5 From cyclohex-2-enones and allene, 8-methylenebicyclo[4.2.0]octan-2-ones are formed regiose-lectively.6 In contrast, six-membered a,/i-unsaturated lactones and allene afford mixtures of regioisomers.7 Mechanistic arguments for the stereochemical outcome of allene photocycloadditions to steroidal enones have been discussed.8... 

Four-membered heterocycles are easily formed via [2-I-2] cycloaddition reac tions [65] These cycloaddmon reactions normally represent multistep processes with dipolar or biradical intermediates The fact that heterocumulenes, like isocyanates, react with electron-deficient C=X systems is well-known [116] Via this route, (1 lactones are formed on addition of ketene derivatives to hexafluoroacetone [117, 118] The presence of a trifluoromethyl group adjacent to the C=N bond in quinoxalines, 1,4-benzoxazin-2-ones, l,2,4-triazm-5-ones, and l,2,4-tnazin-3,5-diones accelerates [2-I-2] photocycloaddition processes with ketenes and allenes [106] to yield the corresponding azetidine derivatives Starting from olefins, fluonnaied oxetanes are formed thermally and photochemically [119, 120] The reaction of 5//-l,2-azaphospholes with fluonnated ketones leads to [2-i-2j cycloadducts [121] (equation 27)... 

A novel intramolecular photocycloaddition involving vinylogous amides and allenes led to an interesting type lb entry to functionalized pyrroles <060L4031>. For example, photolysis of allene 11 provided fused pyrrole 12 via a [2+2] cycloaddition and retro-Mannich reaction. 

Allenes behave as somehow special olefins in such photocycloadditions 476a,b,477) Additions of enones to allene have been used as key step in the synthesis of the alkaloids annotinine 478a) (4.65) and chasmanine (4.66) 478b). 

Photocycloaddition of allene to cyclohexenone (341) gave the (3,y-enone (342), which reacted with vinyl magnesium bromide to produce the tertiary alcohol (343) in 79% yield. When the compound (343) was treated with KH and 18-crown-6 in THF at room temperature for two hours and quenched with aq. NH4C1, the cyclobutene (344) was obtained. The thermal ring opening of the cyclobutene (344) proceeded in toluene in a sealed-tube at 180 °C for twelve hours to give a readily separable 5 1 mixture of the civ-olefin (345), and the trans-olefin (346) respectively in 95 % yield. Moreover, (345) could be converted to a mixture of (346) and (345) in the ratio of 10 1 by irradiation. The compounds (345) and (346) possess the skeleton of the germacranes (347), (348) and (349) 122). 

The [2 + 2] photocycloaddition reaction of enones with allenes was first reported in 1966. A diradical intermediate is formed from a triplet enone via an exciplex. The triplet diradical cyclizes to the product after spin inversion to the singlet state [31,32]. 

Although most of the photocycloaddition reactions have involved olefins, there are several examples of additions to other types of un-saturated systems (e.g., allenes, acetylenes, ketenimines, etc.) which extend their synthetic utility. It is impossible, at this time, to define the limitations of the reaction as applied to other systems however, this will unquestionably be an active and fruitful area of research in the future. 

With conjugated dienes, photocycloaddition of carbonyl compounds occurs at one of the double bonds to give vinyloxetanes. An interesting example is the reaction of acetone with 2-methyl-l,3-butadiene, which gave the two oxetanes (60) and (61) in a ratio of 3 1 and a total yield of about 20% (72JA8761). Other alkenes which have been used for photosynthesis of oxetanes include enol ethers, ketene acetals, enamines, allenes and diketene, with the reaction of the last compound with benzaldehyde illustrated in equation (105) (75CPB365). 

Photochemical reactions of quinones with allenes have also been studied and in some cases cyclobutane formation occurs, although in competition with products derived from attack of the allene on the carbonyl oxygen. Thus, photocycloaddition of tetramethyl-l,4-benzoquinone with 1,1-dimethylallene affords the four-membered carbocycle 6 in good yield.12... 

Recently, Carreira and coworkers126 obtained very high asymmetric induction (83-100%) in intramolecular [2 + 2] photocycloadditions of 1,3-disubstituted allenes with enones 289 and 290 (Scheme 63). 

Para photocycloaddition of arenes to the benzene ring was first reported in 1971 by Wilzbach and Kaplan [7] as a minor process accompanying ortho and meta photocycloaddition. Since that time, relatively few cases of para photocycloaddition have been described. Para adducts were found as minor products from benzene with cyclobutene [8], ra- 3,4 - dimethyIcycIobu(ene [9], vinylene carbonate [10], 2,3-dihydropyran [11,12], and 1,3-dioxole [13,14] and from a,a,a-tri-fluorotoluene with vinylene carbonate [15], Intermolecular para photocycloadducts were major products from the irradiations of benzene and allene [16,17], benzene and cyclonona-1,2-diene [16,17], and from fluorobenzene and cyclopentene [18], Intramolecular para photocycloadducts were found as major products from the irradiations of phenethyl vinyl ether [19-21] (Scheme 3) and 2,3-dimethyl-6-phenylhex-2-ene [22], No detailed mechanistic investigations have been published. 

But amazing contortions are possible. Photocycloaddition of the allene 31 unites just one of the allene bonds with the conjugated alkene to give the very strained cyclobutane 32. Diagram... 

The formation of trans-products is observed to a lesser extent in the reaction of 3-alkoxycarbonyl-substituted cyclohexenones, in the reaction with electron-deficient alkenes and in the reaction with olefinic reaction partners, such as alkynes and allenes, in which the four-membered ring is highly strained (Scheme 6.11). The ester 26 reacted with cyclopentene upon irradiation in toluene to only two diastereomeric products 27 [36]. The exo-product 27a (cis-anti-cis) prevailed over the endo-product 27b (cis-syn-cis) the formation of trans-products was not observed. The well-known [2 + 2]-photocycloaddition of cyclohexenone (24) to acrylonitrile was recently reinvestigated in connection with a comprehensive study [37]. The product distribution, with the two major products 28a and 28b being isolated in 90% purity, nicely illustrates the preferential formation of HH (head-to-head) cyclobutanes with electron-acceptor substituted olefins. The low simple diastereoselectivity can be interpreted by the fact that the cyano group is relatively small and does not exhibit a significant preference for being positioned in an exo-fashion. 

The intermolecular [2 + 2]-photocycloaddition of para-tetrahydronaphthoqui-nones has been applied by Ward et al. to the synthesis of cyathin diterpenes [52], An example is represented by the total synthesis of ( )-allocyathin B3 (46), during the course of which the diastereoselective [2 + 2]-photocycloaddition of allene to substrate 44 served as one of the pivotal steps (Scheme 6.17) [53]. The addition delivered a mixture of regioisomers (r.r. = 80/20), from which compound 45 was separated. The facial diastereoselectivity was perfect due to the concave shape of the quinone. 

A very useful extension of the de Mayo reaction has been recently introduced by Blechert et al. (Scheme 6.26) [78]. The retro-aldol fragmentation was combined with an intramolecular enantioselective allylation (asymmetric ring-expanding allylation) catalyzed by a chiral Pd complex. Bicycloheptane 68, for example, was accessible by intermolecular [2 + 2]-photocycloaddition of cyclopentenone 67 with allene. Further transformation in the presence of Pd2(dba)3 (dba = dibenzylideneacetone) and the chiral oxazoline ligand 69 (tBu-phox) resulted in the enantioselective formation of cycloheptadione 70. 

Substrates A3 (Q = O) have been employed not only as starting materials for fragmentation reactions but also to probe novel stereoselectivity concepts. The photochemical transformation of axial chirality into central chirality was achieved by Carreira et al., who employed chiral, enantiomerically pure allenes in intramolecular [2 + 2]-photocycloaddition reactions (Scheme 6.27) [79]. The reaction of enantiomerically pure (99% ee) cyclohexenone 71, for example, yielded the two diastereomeric products 72a and 72b, which differed only in the double bond configuration. Apparently, the chiral control element directs the attack at the allene to its re face. The double bond isomerization is due to the known configurational liability of the vinyl radical formed as intermediate after the first C—Cbond formation step (see Scheme 6.2, intermediate C). 

Vinylogous thioesters (A3, Q = S) have been used less frequently in [2 + 2]-photocycloaddition as compared to their oxygen and nitrogen analogues [83], More recent applications can be found in the above-mentioned study with chiral allenes [79]. 

The crossed intramolecular [2 + 2]-photocycloaddition of allenes to a, 3-unsat-urated y-lactones has been extensively studied by Hiemstra et al. in an approach to racemic solanoedepin A (87). The sensitized irradiation of butenolide 85 in a 9 1 mixture of benzene and acetone, for example, led selectively to the strained photocycloadduct 86 (Scheme 6.31) [89]. The facial diastereoselectivity is determined by the stereogenic center, to which the allene is attached. The carbon atom in exposition to the carbonyl carbon atom is attacked from its re face, forming a bond to the tertiary allene carbon atom, while the P-carbon atom is being connected to the internal allene carbon atom by a si face attack. The method allows facial diaster-eocontrol over three contiguous stereogenic centers in the bicyclo[2.1.1]heptane part of the natural product. 

The photocycloaddition of a variety of carbonyl compounds with methyl-substituted allenes has been reported to proceed with high quantum yields (0.59 for acetophenone/tetramethylallene) [69] to give 1 1 and 1 2 adducts [70]. The 2-alkylideneoxetanes are useful precursors for cyclobutanones, e.g., 79a,b from the benzophenone/tetramethylallene-cycloadduct 78 (Sch. 22) [71]. 

Some of the earliest work on the [2 + 2] photocycloaddition chemistry of vinylogous imides was reported by Wiesner and coworkers, who described the isolation of the [2 + 2] photoaddition products resulting from the irradiation of cyclic vinylogous imides with ethyl acrylate and allene, respectively (Scheme 12)29. 

A key step in the synthesis of 12-epi-lycopodine reported by Wiesner and coworkers is the intramolecular [2 + 2] photocycloaddition of a vinylogous imide and an allene. Irradiation of photosubstrate 46 produced a single cyclobutane 47, in which the allene added to the vinylogous imide anti to the methyl group (Scheme 13)31. Photoadduct 47 was converted to ketal-alcohol 48 via a three-step sequence of ketalization, epoxida-tion and reduction. Hydrolysis of the ketal unmasked the /Miydroxy ketone functionality. Retro-aldol fragmentation followed by aldol closure gave hydroxyketone 49, which was readily converted to the polycyclic alkaloid 12-epi-lycopodine. 

Photocycloadditions with Cumulated Double Bonds. Wiesner discovered that the regioselectivity in intermolecular cycloadditions of allene to Q, 3-unsaturated ketones 8.50 gave the cyclobutane 8.51 with the central carbon of the allene bonded to the a position. The addition also took place with high stereoselectivity for attack on the lower face of the double bond in 8.50, surprisingly, because the lower face is the more hindered. The approach... 

Alkenes, perfluoro-cycloadditions to benzyl azide, 60, 35 pyridine imines and ylids, 60, 36 Alkenes, perfluoro-, as heterocyclic precursors, 59, 10 Alkylation, free-radical, of 1,3-dimethyluracil, 55, 227 A-Alkylation, [ 1,2,4]triazolo[ 1,5-u)-pyrimidines, 57, 110 Alkynes, photocycloaddition to uracils, rearrangement with HCNO elimination, 55, 149 Alkynes, ethoxy-, cyclaoddition to hexafluoroacetone azine, 60, 32 Alkynes, perfluoro-, as heterocyclic precursors, 59, 10 Allenes... 

Even more rare are photocycloadditions involving carbonyl compounds to allenes. Arnold has found that acetone and tetramethylallene can be irradiated to form a mixture of 2-alkylideneoxetane and 1,3- and l,6-dioxaspiro[3,3]heptane products (107 108 109 = 8 31 27), all resulting from initial attack of the carbonyl n,ir state on the central carbon linkage. Hammond subsequently repented a study in which alkylideneoxetane derivatives (111) were photoisomerized to cyclobutanes (110). 

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