Photocycloadditions enones with alkenes

Scheme 6.10. Photocycloadditions of Enones with Alkenes and Alkynes... 

Introduction of chiral auxiliaries in the starting materials is very attract for applications to organic synthesis. However, to be of synthetic interest, chiral auxiliaries have to be inexpensive, readily introduced on the starting ma rial, inert in the conditions of irradiation, and readily removed from the photo ducts. Even if the first requirements can be easily satisfied with chiral ket esters, and amides, it is often difficult to avoid side reactions involving auxiliary [63]. In order to control all the asymmetric centers created in the in molecular photocycloadditions of cyclic enones with alkenes, esters of c alcohols were first considered. Although menthyl and bomyl derivatives ga only low de, 8-phenylmenthyl esters produced a far better asymmetric inducti [64]. The facial selectivity was found to depend on the syn/anti nature of t cycloadducts and the structure and location of the chiral auxiliary on either tl enone or the alkenyl moiety. More surprisingly the selectivity also depe strongly on the nature of the solvent (Scheme 21). 

The mechanism of the 2 + 2 photocycloaddition of enones with alkenes, which can be viewed as the Bauslaugh-Schuster-Weedon biradical mechanism, is represented in Scheme 10 [66],... 

Scheme 10. Mechanism of [2 -F 2] photocycloaddition of enones with alkenes.

Scheme 13. [2 + 2] Photocycloaddition of enones with alkenes Asymmetric induction by chiral centers of the alkenes.

In cycloadditions of enones to alkenes novel strategies have been adopted for ring expansion of the cycloadducts, either by the choice of appropriate alkenes, e.g. 2-(trimethylsiloxy)buta-1,3-diene,70 vmv-2-trimethylsiloxybuten-2-oales71 or 3,3-dimethylcyclopropene,72 or by using 3-oxo-l-cyeloalkene-l-carboxylates as enones.73 Asymmetric [2 + 2] photocycloaddition of cyclopent-2-enone to a (+ )-dihydrofuran acetonide constitutes the cornerstone of the synthetic strategy in the first total synthesis of the novel antitumor metabolite ( )-echinosporin.74 The cycloaddition product 25 from treatment of 2-(2-carbomethoxyethyl)-2-cyclopentenone (24) with ethene has been used as a precursor for the preparation of tricyclo[4.2.0.01,4]octane.75... 

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. 

Orfanopoulos et al. studied the photochemical reaction of alkenes, aryalkenes, dienes dienones, and acyclic enones with [60]fullerene to obtain various substituted cyclobutylfullerenes [240,241,243,247], For example, the photocycloaddition of cis- and Irans-1 -(p-mcthoxyphenyl)-1 -propenc 68 to C6o gives only the trans [2 + 2] adducts (Scheme 27), thus the reaction is stereospecific for the most thermodynamically stable cycloadduct. A possible mechanism includes the formation of a common dipolar or biradical intermediate between 3C o and the arylalkene. Subsequent fast rotation of the aryl moiety around the former double bond leads exclusively to the trans-69 [2 + 2] adduct. Irradiation of this product, yielded 90% trans-68,10% cis-68 and cycloreversion products. Thus, a concerted mechanism can be excluded because the photocycloreversion is expected to give the trans-68 as the only product. These results can be explained by the formation of a common dipolar or diradical intermediate. Similarly, cycloreversion products from C6o and tetraalkoxyethylene... 

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... 

Photoaddition reactions have also been described with (84) as the substrate.(2+2)-Photocycloaddition of simple alkenes to these enones results in the formation of the adducts (85) and phenylacetylene undergoes similar addition to this substrate. A substituent effect has been detected in these... 

In addition to the examples with alkene substitution, photocycloadditions of enones containing optically active ester substituents were investigated. Irradiation of a toluene solution of cy-clopentene and the chiral enone esters 13a-c gave two types of diastereomeric adducts, cis-anti-cis 14a-c and cis-syn-cis 15a-c77. By varying the size of the chiral auxiliary R the cyclobutane ring junctions syn- vs. anri-adducts) as well as the degree of asymmetric induction is altered. It is possible to obtain high enantiomeric excesses (e.g., 79% for 15a). 

Siloxanes have also been used as temporary tethers to bridge an enone and alkene [70]. Intramolecular [2 + 2] photocycloaddition of 56 provides exclusively straight adduct 57 consistent with the Rule of Five. This product can then be transformed into diol 58 after cleavage of the siloxane tether. (See Scheme 16.)... 

The importance of steric hindrance on facial selectivity is illustrated first for asymmetric cycloalkenes. High facial selectivity is observed with cycloalkenes having one stereogenic center in an allylic position. Photocycloaddition of cyclopentenone 25 with cycloalkene 26 led to a mixture of regio-isomers 27 and 28, resulting in a selective cycloaddition of the excited enone from the diastereoface opposite the large isopropyl group [69], Similar results are observed with alkenes 32, 35, and 38 [70-73] (Scheme 13). 

Enantioselective 2- -2 Photocycloadditions. When 2-l-2 photocycloadditions of prochiral enones and alkenes are carried out in chiral fluid solutions, asymmetric induction could be expected on the new asymmetric centers. Unfortunately, successful examples of such enantioselective syntheses of chiral cyclobutanes have not yet been reported. However, a formal enantioselective 2 -f 2 photocycloaddition can be represented by a three-step sequence, as shown in Scheme 25, where a functional group such as a carboxylic acid can be modified easily and reversibly by simple reaction with a chiral auxiliary. The photochemical reaction can then be carried out with chiral enones or alkenes. 

Andrew D, Hastings DJ et al (1992) Triplet 1,4-biradical intermediates in the photocycloaddition reactions of enones and N-acylindoles with alkenes. Pure Appl Chem 64 1327-1334... 

As previously established, the mechanism of the [2-1-2]-photocycloaddition of cyclopentenones with alkenes can be summarized as shown in Scheme 1. The interaction of the alkene with the enone, excited... 

On the basis of the regiochemistry and the relative rate factors observed in his studies of aUcene additions to photoexcited CH (see above), Corey proposed in 1964 that the first step of the [2-1-2]- photocycloaddition of enones to alkenes involved interaction of a polarized enone triplet excited state with the ground-state alkene to give an oriented Tt-complex (illustrated in structure 27) for the case of addition of CH to methoxyethene. 

A very remote secondary H/D isotope effect has been measured for the 2 + 2-cycloaddition of TCNE to 2,7-dimethylocta-2,fran -4,6-triene. The reaction of nitric oxide with iV-benzylidene-4-methoxyaniline to produce 4-methoxybenzenediazonium nitrate and benzaldehyde is thought to proceed via a 2 + 2-cycloaddition between nitric oxide and the imine double bond. A novel mechanism for the stepwise dimerization of the parent silaethylene to 1,3-disilacyclobutane involves a low-barrier [1,2]-sigmatropic shift. Density functional, correlated ab initio calculations, and frontier MO analysis support a concerted 2 + 2-pathway for the addition of SO3 to alkenes. " The enone cycloaddition reactions of dienones and quinones have been reviewed. The 2 + 2-photocycloadditions of homochiral 2(5H)-furanones to vinylene carbonate are highly diastereoisomeric. ... 

Recent studies by Schuster and collaborators67,54, based on nanosecond laser flash techniques, revealed important conclusions, including (a). The enone excited state responsible for the photocycloaddition is the jt-Tt which possesses different polarization than the n-7T state, considered in rationalizing the effect of the oriented jr-complex. (b) Direct measurement of the reactivity scale of alkenes measured by nanosecond flash photolysis provided different results from those obtained with no consideration of the diradical fragmentation to starting materials. 

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