Intermolecular -Photocycloaddition Approach

The fact that all approaches employing the intermolecular photocycloaddition key step used the same precursor for the construction of the four-membered ring renders enone 6 the key intermediate of the different synthetic strategies. It is therefore sensible to compare first the different strategies to synthesize precursor 6. Afterwards, the different ways to complete the syntheses of kelsoene will be discussed. 

In conclusion, the three groups which applied the intermolecular photocycloaddition as the key step in their approach to kelsoene (1) reported different strategies to synthesize the irradiation precursor 6 in racemic or enantiomerically pure form. After the photocycloaddition step the syntheses of kelsoene were completed in different ways. The next section describes the different strategies employed in the second half of the way to kelsoene. 

Alternative approaches that have been explored for control of photochemical reactions include irradiation in liquid crystals [7], micelles [8], inclusion complexes [9], and zeolites [10]. In addition, photochemistry of monolayers [11] and on surfaces [12] (e.g., alumina, silica, clays, and semiconductors) has received considerable attention. Each of these methods has potential for regiocontrol and/or stereocontrol of certain photochemical processes. However, reactions between different groups (e.g., intermolecular photocycloadditions) are difficult to modulate with most of these approaches. 

Dioxinones (194) can be prepared as enantiomerically pure compounds. The intramolecular 2 -I- 2 photocycloaddition of 194 usually leads to a mixture of two regioisomers, 195 and 196, and even to only isomer when m = 2 and w = 0. The principle merit of this approach resides in the ability of the ester and ketalic groups in the photoadducts to be cleaved easily into adducts similar to those provided by intermolecular photocycloaddition of dioxinones with the corresponding alkenes [159d]. Only one stereoisomer... 

Both target compounds discussed in this review, kelsoene (1) and preussin (2), provide a fascinating playground for synthetic organic chemists. The construction of the cyclobutane in kelsoene limits the number of methods and invites the application of photochemical reactions as key steps. Indeed, three out of five completed syntheses are based on an intermolecular enone [2+2]-photocycloaddition and one—our own—is based on an intramolecular Cu-catalyzed [2+2]-photocycloaddition. A unique approach is based on a homo-Favorskii rearrangement as the key step. Contrary to that, the pyrrolidine core of preussin offers a plentitude of synthetic alternatives which is reflected by the large number of syntheses completed to date. The photochemical pathway to preussin has remained unique as it is the only route which does not retrosynthetically disconnect the five-membered heterocycle. The photochemical key step is employed for a stereo- and regioselective carbo-hydroxylation of a dihydropyrrole precursor. 

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]. 

Semiempirical calculations on the 2+2 photocycloaddition between two propene molecules has suggested that there is a preference for a head-to-tail approach and a concerted pathway [7]. The authors suggest that intermolecular cycloaddition between alkenes with electron withdrawing groups should favor formation of the nms-l,3-disubstituted cyclobutane. 

The scope of this approach was widened by the observation of excellent enantioselectivities in intermolecular [2+ 2]-photocycloaddition reactions with various alkenes [62,71]. In the presence of an excess amount of alkene, 4-me thoxy-2-quinolone (57) was converted with high chemo- and regioselectivity to the exo and endo cyclobutanes 59 and 60. With 4-penten-1-ol (58a), allyl acetate (58b), methyl acrylate (58c), and vinyl acetate (58d), the exo diastereomers 59a-d were formed with high simple diastereoselectivity and in high yields (80-89%), Under optimized irradiation conditions (2.4 eq. of host 44 or ent-44, — 60°C), high enantiomeric excesses were achieved in all instances, as depicted in Scheme 22. These enantiomeric excesses are unprecedented for an intermolecular photochemical reaction. 

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... 

In general, intermolecular [2 -I- 2] photocycloaddition of simple alkenes does not show satisfactory regioselective control. An approach to improve the reaction selectivity is use of a tether to constrain the reactive alkene functional groups proximate to each other and therefore allow the photocycloaddition to proceed. Tethers which have been employed include sugar alcohols such as d-maimitol and L-erythritol [101], diazacrown ethers [102], cyclophane [103], and silanes [104]. In all cases, the tether preorganized alkenes yield head-to-head adducts. The silane-tethered method can bind different alkene groups as well as alkynes, as shown in Scheme 27 [105]. Photoreactions of polyacetylenes and alkenes have also been investigated [106]. 

Sano T, Toda J, Ohshima T, Tsuda Y (1992) Synthesis of Erythrina and Related Alkaloids. XXX. Photochemical Approach. (1). Synthesis of Key Intermediates to Erythrina Alkaloids by Intermolecular [2 - - 2] Photocycloaddition Followed by 1,3-Shift. Chem Pharm Bull 40 873... 

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