Photocycloaddition diastereoselective

Upon irradiation with X > 300 nm, the 4-alkenyloxy-2-quinolones 23 and 25 cyclized in an intramolecular [2+2]-photocycloaddition diastereoselectively to the crossed and straight cycloadducts 24 and 26, respectively. In the presence of 2.6 equivalents of host compound 21 or ent-21, high enantioselectivities were achieved in a nonpolar solvent at low temperatures." " At -60°C in toluene, 24 and 26 were obtained with >90% ee (Scheme 10). Higher temperatures (84% ee at -15°C, 39% ee at 30°C) and more polar solvents (4% ee at 30°C in acetonitrile) significantly reduced the enantioselectivity under otherwise identical conditions. 

The enol ether double bond contained within the ds-fused dioxa-bicyclo[3.2.0]heptene photoadducts can also be oxidized, in a completely diastereoselective fashion, with mCPBA. Treatment of intermediate XXII, derived in one step from a Patemo-Buchi reaction between 3,4-dimethylfuran and benzaldehyde, with mCPBA results in the formation of intermediate XXIII. Once again, consecutive photocycloaddition and oxidation reactions furnish a highly oxygenated system that possesses five contiguous stereocenters, one of which is quaternary. Intermediate XXIII is particularly interesting because its constitution and its relative stereochemical relationships bear close homology to a portion of a natural product known as asteltoxin. 

High facial diastereoselectivity has been reported in the [2+2] photocycloaddition of aromatic aldehydes with a chiral enamide to give the ds-2,3-disubstituted oxetanes 11 and 12 with only minor amounts of the trans-oxetanes <99TL9003>. The same group of workers have investigated the photocycloaddition of m-substituted benzaldehydes to 3,4-dihydro-l.H-pyridin-2-ones to give mainly 13 <99JA10650>. 

In addition to the [4+2] cycloaddition, intramolecular [2+2] photocycloaddition was also successfully used as a main procedure in the synthesis of (i)-ginkgolide B <00JA8453>. The studies on the model reactions and molecular mechanics calculation show that the stereochemistry of the substituents at C6 and C8 should influence severely the reaction diastereoselectivity. When syn-diastereomer 41 is subjected to irradiation the reaction gives a single diastereomer 42 in a quantitative yield since two substituents at C6 and C8 would be in pseudo-equatorial orientation in the chair-like transition state. 

In contrast to the preceding syntheses of kelsoene. Piers and Orellana used ethylene 8 in the [2-1-2]-photocycloaddition key step to furnish tricyclic ketone rac-lO diastereoselectively (Scheme 2) [11]. In accordance with the report by Srinivas and Mehta, attempts to homologate the sterically encumbered ketone rac-lO using the Wittig, Magnus [18, 19] or Taguchi [20] pro-... 

Photocycloadditions of silyl enol ethers 362 with aromatic aldehydes 363 have been used to prepare substituted oxiranes with high diastereoselectivities favoring the isomer... 

The diastereoselectivity with which butenoxy acetophenones undergo intramolecular [2 + 2] photocycloadditions has been studied by Wagner and Cheng... 

Wagner and McMahon [101] have irradiated compounds bearing chiral auxiliaries and observed that high diastereoselectivity can be achieved with photoinduced intramolecular ortho cycloaddition (Scheme 26). Carbon atom 8 is the only permanent new stereocenter created by the ortho photocycloaddition. WhenX = (2R,5R)-( )-2,5-dimethylpyrrolidine or(7/ )-H Fcamphorsultam, di-astereomeric excesses as high as 90% are obtained. The (85)-cyclooctatriene-sul-tam derivative could be isolated as a single diastereomer after one recrystallization. 

Sugimura et al. investigated diastereoselectivity in the photocycloaddition of arene and alkene connecting by optically active 2,4-pentanediol [239], High di-astereofacial differentiation was observed at the addition step and sufficient re-giocontrol of the subsequent ring-closure step. 

Diastereoselectivity in the (3 + 2) photocycloaddition of di-( )-menthyl, di-( )-8-phenylmenthyl, and di-( )-bomyl derivatives (398b-d) is largely dependent on the concavity of the auxiliary, steric bulk of the substituents of the alkenes, and reaction temperature [365] (Scheme 107). The highest de value was obtained when 8-phenylmenthyl ester 398c was employed, although the yield of the adducts was relatively low. The bomyl ester 398d showed poor diastereoselectivity. The effect of the chiral auxiliary seems to be reasonably explained in terms of the concavity of the auxiliary. When a-methylstyrene was used as the alkene, two stereoisomers of (3 + 2) adducts were obtained in lower yields than... 

It will be interesting to follow the developments on the highly efficient and more stereoselective photocycloaddition and photoaddition to aromatic rings from the viewpoints for the synthesis of more complex compounds, including natural products. In addition, the chiral induction in the excited states should be more attractive projects in the near future. Although some excellent reviews about the asymmetric photochemical reactions have been reported in recent years [490-492], the highly enantioselective or diastereoselective photocycloaddition and photoaddition have been reported in only limited cases. 

An intramolecular [2+2] photocycloaddition of allyl ethers with dioxinones followed by a base-induced fragmentation leads to substituted tetrahydropyran-4-ones <1997TL5579>. A one-pot scandium triflate catalyzed diastereoselec-tive cyclization between aldehydes and (3-hydroxy dioxinones 1046 followed by alkoxide addition to the resulting bicycles 1047 leads to 3-carboxy-substituted tetrahydropyran-4-ones 1048 with high levels of diastereoselectivity as a mixture of keto/enol tautomers (Scheme 268, Table 49) <20050L1113>. 

Wagner, P.J. and McMahon, K. (1994) Chiral auxiliaries promote both diastereoselective cycloaddition and kinetic resolution of products in the ortho photocycloaddition of double bonds to benzene rings. Journal of the American Chemical Society, 116, 10827-10828. 

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]. 

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. 

Control over the absolute configuration in cyclohexenone photocycloadditions has been achieved by auxiliary-induced diastereoselectivity. In particular, esters related to compound 26, which are derived from a chiral alcohol but not from methanol, lend themselves as potential precursors, from which the chiral auxiliary can be effectively cleaved [42, 43]. In a recent study, the use of additives was advertised to increase the diastereomeric excess in these reactions [44], An intriguing auxiliary-induced approach was presented by Piva et al., who employed chiral 13-hydroxy-carboxylic adds as tethers to control both the regioselectivity and the diastereoselectivity of intramolecular [2 + 2]-photocycloaddition reactions [45]. In Scheme 6.14 the reaction of the (S)-mandelic acid derived substrate 38 is depicted, which led with very good stereocontrol almost exclusively to product 39a, with the other diastereoisomer 39b being formed only in minor quantities (39a/39b = 96/4). Other acids, such as (S)-lactic acid, performed equally well. The chiral tether could be cleaved under basic conditions to afford enantiomerically pure cydobutane lactones in good yields. 

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. 

The [2 + 2]-photocycloaddition chemistry of a,(3-unsaturated lactones has been widely explored. The factors governing regio- and simple diastereoselectivity are similar to what has been discussed in enone photochemistry (substrate class Al, Section 6.2). The HT product is the predominant product in the reaction with electron-rich alkenes [84]. A stereogenic center in the y-position of ot,P-unsaturated y-lactones (butenolides) can serve as a valuable control element to achieve facial diastereoselectivity [85, 86]. The selectivity is most pronounced if the lactone is substituted in the a- and/or P-position. The readily available chiral 2(5H)-furanones 79 and 82 have been successfully employed in natural product total syntheses (Scheme 6.30). In both cases, the intermediate photocycloaddition product with 1,2-dichloroethylene was reductively converted into a cyclobutene. In the first reaction sequence, the two-step procedure resulted diastereoselectively (d.r. = 88/12) in product 80, which was separated from the minor diastereoisomer (9%). Direct excitation (Hg lamp, quartz) in acetonitrile solution was superior to sensitized irradiation (Hg lamp, Pyrex) in acetone, the former providing the photocycloaddition products in 89% yield, the latter in only 45%. Cyclobutene 80 was further converted into the monoterpenoid pheromone (+)-lineatin (81) [87]. In the second reaction... 

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. 

If the stereogenic center carries a tethered alkene, the diastereoface selectivity is dictated by the direction of the tether. Diene 131 underwent a diastereoselective [2 + 2]-photocycloaddition to the products 132 of a bottom approach relative to the six-membered dioxenone ring (Scheme 6.46). The simple diastereoselectivity was not perfect, however. The endo-product 132a was preferred over the exoproduct 132b [127]. 

The intramolecular photodimerization and [2 + 2]-photocycloaddition in DNA involves thymine or cytosine as the chromophore. This chemistry has been intensively investigated with regards to DNA damage and repair [131]. Despite the fact that the area is of continuous interest [132], the synthetic applications are limited and are not covered here in detail. However, some preparative aspects of 4-pyrimidinone photocycloaddition chemistry will be addressed. Aitken et al. have prepared a plethora of constrained cyclobutane P-amino acids by intra- or intermolecular [2 + 2]-photocycloaddition to uracil and its derivatives [133, 134]. In a chiral adaptation of this method, the uracil-derived enone 140 was employed to prepare the diastereomeric cyclobutanes 141 in very good yield (Scheme 6.49). The compounds are easily separated and were - despite the relatively low auxiliary-induced diastereoselectivity - well suited to prepare the as-2-aminocyclobutanecarboxylic acids 142 in enantiomerically pure form. Enantioselective access to the corresponding trans-products was feasible by epimerization in a-position to the carboxyl group [135],... 

Tsutsumi, K., Nakano, H., Furutani, A., Endou, K., Merpuge, A., Shintani, T., Morimoto, T., and Kakiuchi, K. (2004) Novel enhancement of diastereoselectivity of [2 + 2] photocycloaddition of chiral cyclohexenones to ethylene by adding naphthalenes. Journal of Organic Chemistry, 69, 785-789. 

Redon, S. and Piva, O. (2006) Diastereoselective transannular [2 + 2] photocycloadditions of ascorbic add derivatives. Tetrahedron Letters, 47, 733-736. 

Photocycloaddition reactions of aromatic aldehydes with cyclic ketene silylacetates have been investigated by Abe and coworkers [61]. Regio- and diastereoselective formation of the bicyclic 2-alkoxyoxetanes 69 was observed in high yields. Hydrolysis of these acid-labile cycloadducts with neutral water efficiently gave aldol-type adducts 70 with high threo-selectivity (Sch. 18). 

The photocycloaddition of methyl arylglyoxylates 90 with cyclo-1,3-dienes was investigated by Hu and Neckers (Sch. 26) [87]. These reactions proceed with high regioselectivity whereas the diastereoselectivity strongly depends on the nature of the aryl substituent. 

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