Enone + alkene photocycloaddition regioselectivity

In contrast to these intermolecular enone + alkene photocycloadditions, the regioselectivity in the corresponding intramolecular cycloisomerizations of alkenylcycloalkenones is controlled primarily by... 

The course of intramolecular enone alkene photocycloaddition is dependent on the number of atoms between the two reactive C=C bonds. For example, E- and Z-isomers of 1-acylhepta-1,6-diene (147) form a 1 1 mixture of stereoisomeric cycloadducts 148 and 149 upon irradiation, while no E Z isomerization occurs (Scheme 6.67a).764 The initial bonding takes place between the C2 (Cp) and C6 atoms, in agreement with the empirical rule of five,165 the regioselective, kinetically preferred formation of five-membered ring biradical intermediates over larger rings due to the entropies of cyclization. As a result, the biradical 150 is not observed. For comparison, the acylhexadiene 151 photolysis also proceeds via a 1,4-biradical (152) formed by an initial 1,5-cyclization (Scheme 6.67b).766... 

Schuster s and Weedon s results support Bauslaugh s proposed mechanism that emphasizes the effect of the ratio between cyclization and the alternative fragmentation pathway of the diradical intermediate, on the regioselectivity in the intermolecular photocycloadditions, and propose not to consider the oriented 7r-complex (exciplex) as an intermediate in the mechanistic pathway of the [2 + 2] photocycloaddition of enones to alkenes. 

Prediction of the regioselectivity in the intermolecular photocycloaddition of enones to alkenes following this method provides similar results to those rationalized by the oriented -complex. However, it is in contrast with Weedon s previously discussed trapping results which indicate no selectivity in the first bond formation at the a- or /J-carbon positions in cyclic enones. 

In the preparative application of [2 + 2]-photocycloadditions of cyclic enones to (substituted) alkenes, two factors concerning product formation are of decisive relevance, namely the regioselectivity and the (overall) rate of conversion. Regarding the regioselectivity in the addition to mono- and 1,1-disubstituted alkenes, Corey had shown that the preferred addition mode of cyclohex-2-enone to isobutene or 1,1-dimethoxyethylene was the one leading to—both cis- and trans-fused—bicyclo[4.2.0]octan-2-ones with the substituents on C(7) [8]. In contrast, in the reaction with acrylonitrile, the alternate orientation was observed to occur preferentially. Similar results were also reported by Cantrell for the photocycloaddition of 3-methyl-cyclohex-2-enone to differently substituted alkenes [14]. No significant differences in the overall rates of product formation for the different alkenes were observed in these studies. In order to explain these observed... 

A preliminary examination of asymmetric induction in photochemical [2 + 2] cycloaddition reaction of an enone to an alkene employed a chiral auxiliary attached to the alkene component74. The photocycloaddition of 2-cyclopentenone to the optically active ketene acetal 1 led both to oxetanes and cyclobutanes in the ratio 6.5 3.5 with a total yield of 60%. The m-[2C + 2C] addition of the chiral alkene I to 2-cyclopentenone was completely regioselective and gave four diastereomeric head-to-tail cycloadducts 2-4 in the ratio 6 29 33 32. 

These two mechanisms, the reversible biradical intermediate and the intermediate exciplex [25] have both been useful for analysis of the regioselectivity and stereoselectivity observed in [2 -I- 2] photocycloaddition between enones and alkenes. Hoffman et al. [26], for example, describes his stereoselective photocycloadditions as arising from a biradical from the triplet excited enone which may or may not involve exciplex formation.. Ground state trans-cycloalkenones have also been proposed as the reactive intermediates which lead to [2 + 2] cycloadducts [27]. The distance between the reacting partners is clearly an issue. If the n systems are not sufficiently close, then photocycloaddition will not occur [28]. 

Investigation of [2 -l- 2] photocycloaddition of enones to monosubstituted alkynes indicates that the reaction proceeds with an opposite regioselectivity compared to that of alkenes [71]. Generally, head-to-head adducts are major products except when the group substituted on the alkyne is -CO2R or -OR (see Scheme 17). Thus, methyl propynoate (60, R = CO2CH3) photoadds to cyclopentenone 59 to give 1 1 HH and HT products. Cycloaddition of cyclohexenone to 1-hexyne has also been studied and the HH HT ratio varies from 2 1 to 7 1 as a function of substituents at the enone 3-position. It... 

Piva et al. have established removable chiral tethers that attach an alkene to an enone and render the intramolecular [2-1-2]-photocycloaddition between these groups highly diastereoselective. Chiral a-and P-hydroxy acids such as (S)-lactic acid, (S)-phenyllactic acid, or (S)-mandelic acid proved to be highly effective auxiliaries. Butenyl lactate 1 was converted regioselectively to the straight adduct 2. The diastereoselectivity reached 94% DE at -40°C, albeit with a reduction in yield. At -20 C, 92% DE and 78% yield were obtained (Scheme 2). 

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