Patai S., Rappoport Z. 1997 The chemistry of functional groups. The chemistry of double-bonded functional groups / 0641 703

B. Stereoselectivity and Synthetic Applications

1. Intermolecular photocycloadditions

The intermolecular photocycloaddition of alkenes to cyclic enones was found to afford cis- and trans-fused bicyclic systems. This stereoselectivity and the diastereofacial selectivity of chiral alkenes and/or enones is discussed below.

a. Ring fusion selectivity. The ring fusion stereoselectivity is affected by the ring size of the cyclic enone and the nature of the alkene (cyclic, substituted etc.). In most cases, photocycloaddition of cyclopentenones provide cis-fused bicyclic products with acyclic alkenes with loss of the alkene configuration via the diradical intermediate, usually providing a mixture of the corresponding endo- and exo-isomeric products. Intermolecular photoaddition to cyclohexenones usually provides trans-fused bicyclic products with acyclic alkenes as obtained in one of the early examples reported by Corey on the photoaddition of 153 to cyclohexenone60. However, cis-fused photoadditions have also been obtained as the major or exclusive photoproduct as found in the photoaddition of 156 to the silylenolether 15786 (Scheme 33).

Cis,anti,cis products are favored in the intermolecular photocycloaddition of cyclopentenones with cyclic alkenes87 (Scheme 34). However, intermolecular photoaddition of some cyclohexenones provided preferred trans-fused product as the major product with cyclic alkenes60. From the large number of examples presented in Schemes 37, 42, 43, 45, 46, 48 and other examples, it could be concluded that cis-fused products are usually preferred.

The structure of the cyclic enone affects the stereoselectivity in the formation of the four-membered ring, as could be seen in the photoaddition of testosterone derivatives 159 and 162 to cyclopentene. Rubin and colloborators88 reported favored cis-fused product

in the addition of trans-stilbene to an optically active fumarate ester in 94% ee. This stereofacial selectivity was claimed to be due to extensive -stacking giving rise to a rigid exciplex 164.

(164)

Another example involves photoaddition of the chiral acetal 165 to cyclopentenone, affording the photoproduct 166 in a considerable enantiomeric excess90 (Scheme 36).

Further studies, on the same principle, were carried out by Lange and coworkers on the intermolecular photocycloadditions of cyclohexenones 167 to alkene 168, possessing different chiral auxiliaries at the enone91 or alkene92. Diastereomeric mixtures of cis,anti,cis 169 and cis,syn,cis isomers were obtained in low to moderate diastereomeric excess (Scheme 37).

Chiral auxiliary on rigid cyclic enones could be expected to afford good facial selectivity. Based on a fairly large number of examples, Wiesner and coworkers93 have proposed two models that allow, to some extent, prediction of the preferred facial selectivity in the intermolecular [2 C 2] photocycloadditions of alkenes or allenes to chiral cyclohexenones. In the first model, they proposed that the excited cyclohexenone adopts a half-chair conformation in its reactive excited state, with a trigonal ˛-carbon and pyramidal ˇ-carbon capable of adapting the more stable configuration and orbital overlap. In the second model, Wiesner assumed a planar excited state in which the ˇ-carbon is pyramidalized in the process of reacting with the olefin, and the more stable biradical, formed at the ˇ- carbon, leads to the product. He also pointed out that the diastereofacial selectivity could be predicted from the selectivity obtained by an alkali metal ammonia reduction of the cyclic enone. Photoaddition of decalone 170 with allene afforded 172 stereoselectively and in 95% yield. The obtained diastereofacial selectivity from the ˛-side is consistent with the transoid anion 173 being responsible for the formation of 174 while structure 171 that presents the triplet excited state with pyramidalization at the ˇ-carbon points to the ˛-side with similar steric and conformational considerations. Further examples could be seen in the irradiation of compounds 175 177 in which all present exclusive or preferred diastereofacial selectivity consistent with the selectivity obtained with similar or related compounds on Li/NH3 reduction (Scheme 38).

ee: after hydrolysis

SCHEME 37

Wiesner and coworkers have emphasized that while the equilibrium constants between the two diastereomeric photoexcited states and anionic intermediates respectively should be similar, there is no reason to expect that they must be numerically identical. Small differences in equilibrium constants could in some cases reverse the stereoselectivity of photocycloaddition with respect to metal reduction. The group of Cargill94 examined the validity of Wiesner’s models by the photoaddition of tert-butylcyclohexenone 178 with ethylene. Irradiation at low temperature ( 78 °C) afforded a mixture of three isomers 179 181, in which the photoproduct 179 is the major product while isomer 180, expected to be the major one based on the first model, was obtained as the minor isomer. This result seems to rule out the first model (it does not take into consideration the reversibility of the first bond formation in the intermolecular photoadditions), however, it is consistent with the second model (Scheme 39).

The first model was used later on to rationalize the experimental fact that photocycloaddition of ethylene to the trans-fused enone 182 proceeded smoothly while the cis-fused

alkenes afforded ca 80% de in both isomers 193 and 195 in a head-to-head fashion and cis,anti,cis-fused products (Scheme 42).

The high facial selectivity found in the thermal and photochemical reactions of chiral 1,3-dioxin-4-ones have triggered increasing interest in both their mechanistic aspects and synthetic applications. Poor facial selectivity was obtained in the intermolecular photoaddition of dioxinone 197a with various alkenes. However, Lange and coworkers98 have succeeded in achieving high facial selectivity in the intermolecular photoaddition of dioxinone 197b with preferred approach of the alkene from the equatorial tert-butyl side. The observed stereoselectivity was attributed to the steric hindrance of the axial methyl at the ketal center (Scheme 43).

SCHEME 43

The above examples have presented a better induction effect when the chiral auxiliary was located at the enone molecule. Double auxiliary induction has been examined by Scharf and coworkers99. Systematic study on the photoaddition of chiral enones 203 to chiral ketene acetals 204 provides examples of matched (45% de) and mismatched (9% de) double stereo differentiation (Scheme 44).

Stereoselective intermolecular photoadditions of alkenes to enones have been elegantly utilized in the synthesis of naturally occurring compounds or compounds of special interest. Sato and collaborators100 have applied the photoaddition of dioxinone 208 to the chiral cis-diol 207 for a one-pot synthesis of the Corey lactone 210, which possesses considerable utility in the preparation of prostaglandin derivatives (Scheme 45).