Double photocycloaddition

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. 

Photocycloaddition of Alkenes and Dienes. Photochemical cycloadditions provide a method that is often complementary to thermal cycloadditions with regard to the types of compounds that can be prepared. The theoretical basis for this complementary relationship between thermal and photochemical modes of reaction lies in orbital symmetry relationships, as discussed in Chapter 10 of Part A. The reaction types permitted by photochemical excitation that are particularly useful for synthesis are [2 + 2] additions between two carbon-carbon double bonds and [2+2] additions of alkenes and carbonyl groups to form oxetanes. Photochemical cycloadditions are often not concerted processes because in many cases the reactive excited state is a triplet. The initial adduct is a triplet 1,4-diradical that must undergo spin inversion before product formation is complete. Stereospecificity is lost if the intermediate 1,4-diradical undergoes bond rotation faster than ring closure. 

Scheme 54 summarizes Font s synthesis of (+)-grandisol (36), the male pheromone of the cotton boll weevil (Anthonomus grandis) [80]. The key-step is the double [2+2] photocycloaddition of ethylene to bis(a,(3-butenohde) A to give B, which yielded C after glycol cleavage. The recently identified pheromone of the oleander scale (Aspidiotus nerii) possesses a structure similar to that of grandisol (Scheme 54), and its synthesis was reported by Ducrot [81 ] and also by Guerrero [82,83]. 

The second reaction mode is rearrangement of the ketocarbene to a ketene. In the presence of a C—C double bond this species reacts further via an intramolecular photocycloaddition (cf. chapter 4.3.3), as shown in (2.23) 238). 

This chapter deals with [2 + 2]cycloadditions of various chromophors to an olefinic double bond with formation of a four-membered ring, with reactions proceeding as well in an intermolecular as in an intramolecular pattern. Due to the variety of the starting materials available (ketones, enones, olefins, imines, thioketones, etc.. . .), due to the diversity of products obtained, and last but not least, due to the fact that cyclobutanes and oxetanes are not accessible by such a simple one-step transformation in a non-photo-chemical reaction, the [2+2]photocycloaddition has become equivalent to the (thermal) Diels-Alder reaction in importance as for ring construction in organic synthesis. 

The key intermediate in Tobe et al. s synthesis of (+)-marasmic acid (27), 1-oxa-spirohexane (26), was accessed via a photocycloaddition between enone 24 and 1 (Scheme 19.6) [8], The photocydoadduct 25 was obtained in 73% yield with the desired isomer consisting of 91% of the material. The structure of the minor product obtained from this cycloaddition was not confirmed. Reduction of the carbonyl group of 25 and epoxidation of the exocyclic double bond gave 26. An acid-catalyzed rearrangement of 26 afforded the core structure of marasmic acid and was subsequently taken on to complete the synthesis of this natural product. 

If there are suitable inter- or intramolecular double-bond contacts, (2 + 2) photocycloaddition is the favored process. 

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. ... 

The photocycloaddition precursor ent-6 was obtained from 19 by transformation into the corresponding acid chloride and AlCl3-mediated intramolecular acylation of the double bond. While the conciseness of this strategy is appealing, drawbacks are the low yields achieved in the individual reaction steps giving ent-6 in an overall yield of only 5%. 

The skeleton of 47 is a heterocyclic tricyclo[6.2.0.0 ]decane and the similarity to the tricyclic kelsoene is obvious. In the course of the above-mentioned studies we had become curious whether the high facial diastereocontrol in the photocycloaddition reaction could be extended to other bridged 1,6-hexadienes. Kelsoene was an ideal test case. The retrosynthetic strategy for kelsoene along an intramolecular [2+2]-photocycloaddition pathway appeared straightforward. To avoid chemoselectivity problems the precursor to kelsoene should not contain additional double bonds. Alcohol 48, the hydroxy group of which was possibly to be protected, seemed to be a suitable substrate for the photocycloaddition (Scheme 14). Access to the 1,2,3-substi-... 

Feldman and Campbell, on the other hand, used hydrogen-bonding interactions to enforce a particular stereo- and regiochemical outcome of the sohd-state photocycloaddition of a naphthoic acid-derived cinnamic acid [45]. In a conceptually similar approach, Scheffer demonstrated that diamines can form double salts with a variety of trans-cinnamic acid derivatives. The locking in place of the double bonds steers the sohd-state [2+2] photodimerization [46]. 

Bishop and Hamer found that acyclic a,/8-unsaturated 1,2-diketones form cyclopentanol derivatives in high yield, while / ,y-unsaturated derivatives form oxetanes by internal cycloaddition.114 Unexpectedly, the y,S-unsatu-rated derivatives also gave oxetanes after an initial migration of the double bond to the /8,y position. The formation of oxetanes such as 38 was observed in the camphorquinone sensitized dimerization of butadiene.115 Photocycloadditions of a-diketones to various olefins have been studied by several groups.116... 

With conjugated dienes, photocycloaddition of carbonyl compounds occurs at one of the double bonds to give vinyloxetanes. An interesting example is the reaction of acetone with 2-methyl-l,3-butadiene, which gave the two oxetanes (60) and (61) in a ratio of 3 1 and a total yield of about 20% (72JA8761). Other alkenes which have been used for photosynthesis of oxetanes include enol ethers, ketene acetals, enamines, allenes and diketene, with the reaction of the last compound with benzaldehyde illustrated in equation (105) (75CPB365). 

Cyclobutane formation via light-induced [2 + 2] cycloaddition is probably one of the best studied photochemical reactions and has been reviewed thoroughly up to 1972 (Houben-Weyl, Vols. 4/5 a and 4/5 b). The most important types of C —C double-bond chromophores undergoing such reactions arc alkenes, 1,3-dienes, styrenes, stilbenes, arenes, hetarenes, cycloalk-2-enones, cyclohexa-2,4(and 2,5)-dienones, 1,4-benzoquinones, and heteroanalogs of these cyclic unsaturated carbonyl compounds. For p notocyciodimerizations see Houben-Weyl, Vol. 4/5 a, p 278 and for mixed [2 + 2] photocycloadditions of these same chromophores to alkenes see Section 1.3.2.3. 

One of the very few examples of a cyclohept-2-enone undergoing photocycloaddition to a C —C double-bond system is the reaction of l,3,10-trimethyl-8-oxabicyclo[5.3.0]dec-3-ene-2,9-dione (35) with 2-trimethylsiloxybuta-1,3-diene (36) to give the desired adduct 37 in 9% yield.115... 

The N=N double bon d does take part in a few photocycloaddition reactions to give cyclic compounds with two adjacent nitrogen atoms in the ring. Intermolecular (2 + 2 cycloadditions are not known, but some intramolecular examples of this reaction are reported for quite complex compounds 15.27 in which the reacting groups are held fairly rigidly in an orientation suitable for reaction. A (4 + 2) cycloaddition takes place when naphthalene is irradiated with an electron-deficient cvdrc azo-compound (5.28). 

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