Photocycloaddition acetals

Wender and Dreyer have demonstrate that meta-areiw photocycloaddition chemistry can lead expediently to modhephene A( tate 7S>5, a photoproduct derived from indane and vinyl acetate was converted to tetracyclic ketone 797 (Scheme XCVI). Because the enolate of 797 partakes of the dynamic behavior of semibuUvalenes, it proved possible to trimethylate the substance to produce 798. A fourth methyl group was introduced by conjugate addition and the carbonyl was simultaneously converted to an olefinic center. Selective hydrogenation of799 provided modhephene in seven steps. 

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). 

Examples of this are the photocycloaddition reactions of 3-methylcyclohex-2-enone with ethene96 and isophoronc with l-propen-2-yl acetate.97 The cycloaddition of isophorone to methyl cyclobutene-1-carboxylate98 or of ( —)-piperitone (28) to 1,2-bis(trimethylsiloxy)cyclo-butene (29)99 affords tricyelo[4.4.0.02 5]deean-7-ones, used as starting compounds in fragmentation reactions. 

Photocycloaddition of ketene acetals with enones gives cyclobutanes which can be converted to cyclobutanones (see Section 1.3.2.3.). When a chiral ketene acetal was used, photocycloaddition with cyclopent-2-enone gave a low yield of the cycloadduct with only 30% enantiomeric excess.23... 

Systematic study on the diastereofacial selectivity in the intramolecular photocycloaddition of alkenes to chiral dioxinones was recently reported by Haddad and coworkers129 on compounds of type 298. Preferred pyramidalization in the direction of the less exposed side (the axial methyl at the acetal center) described in structure 298b, and first bond formation at this position (found to be the case in dioxinones 143 and 146, Scheme 31), are essential features for obtaining selective photocycloadditions of alkenes to chiral dioxinones from this side, leading to the kinetically favored products. In such cases the preferred approach is not necessarily from the more exposed side (Figure 6). 

Meta photocycloaddition was discovered simultaneously and independently by two groups in 1966. Wilzbach and Kaplan [4] found that the adducts from m-but-2-ene, cyclopentene, and 2,3-dimethylbut-2-ene with benzene are substituted tricyclo 3.3.0.02X]oct-3-enes. The adducts were formed by irradiation of solutions (-10%) of the olefins in benzene, at room temperature under nitrogen, with 2537-A light. Bryce-Smith et al. [5] subjected an equimolar mixture of m-cyclooctene at room temperature or in the solid phase at 60°C to ultraviolet radiation of wavelength 235-285 nm. A mixture of 1 1 adducts was obtained from which the main component (-85%) was readily obtained pure by treatment of the mixture with methanolic mercuric acetate. This 1 1 adduct proved to be a meta photocycloadduct (Scheme 2). The minor nonaromatic adduct (10-15%) could, at that time, not yet be obtained completely free from the meta photocycloadduct the structure of a rearranged ortho adduct was provisionally assigned to this isomer. 

Scheme 32 Ortho photocycloaddition of p- and o-methoxyacetophenone to ethyl vinyl ether and vinyl acetate.

Ohashi et al. [128] found that the yields of ortho photoaddition of acrylonitrile and methacrylonitrile to benzene and that of acrylonitrile to toluene are considerable increased when zinc(II) chloride is present in the solution. This was ascribed to increased electron affinity of (meth)acrylonitrile by complex formation with ZnCl2 and it confirmed the occurrence of charge transfer during ortho photocycloaddition. This was further explored by investigating solvent effects on ortho additions of acceptor olefins and donor arenes [136,139], Irradiation of anisole and acrylonitrile in acetonitrile at 254 nm yielded a mixture of stereoisomers of l-methoxy-8-cyanobicyclo[4.2.0]octa-2,4-diene as a major product. A similar reaction occurred in ethyl acetate. However, irradiation of a mixture of anisole and acrylonitrile in methanol under similar conditions gave the substitution products 4-methoxy-a-methylbenzeneacetonitrile (49%) and 2-methoxy-a-methylbenzeneacetonitrile (10%) solely (Scheme 43). 

In enantioselective photocycloaddition reactions, 4-alkoxyquinolones perform in superior fashion to l,5-dihydropyrrol-2-ones and 5,6-dihydro-lff-pyridin-2-ones. Both, intermolecular and intramolecular reactions were performed with excellent enantioselectivity in the presence of the chiral template 115, or of its enantiomer ent-115 [147, 148], The well-established photocycloaddition reactions [149, 150] enabled access to a variety of chiral dihydroquinolones. 4-Methoxyquinolone (157) produced, upon direct irradiation in the presence of allyl acetate, the formal HT product 158 in 80% yield and with 92% ee (Scheme 6.56) [151]. 

The Paterno-Buchi photocycloaddition of silyl 0,X-ketene acetals (with X—O, S, Se) and aromatic aldehydes was intensively investigated by Abe and coworkers in the last decade [62]. The regioselectivity of the reaction (71 vs. 72) is highly affected by the heteroatom (Sch. 19) [63,64]. The regioselectivity is rationalized by (a) the relative stability of the 1,4-biradicals and (b) the relative nucleophilicity of sp2-carbons in the respective 0,X-ketene acetal. 

The photocycloaddition of benzophenone to furan 87a was originally described by Schenck et al. [79]. Additionally to the 1 1 adduct 88 also two regioisomeric 2 1 adducts 89a,b were isolated [80], the structure of 89a was revised by Toki and Evanega [81]. All prostereogenic carbonyl addends when photochemically added to furan showed regioselectivities >99 1 in favor of the bicyclic acetal product (Sch. 25). 

Recently, the effect of hydrogen bonding in the first excited singlet vs. the first excited triplet state of aliphatic aldehydes in the photocycloaddition to allylic alcohols and acetates (147) was compared (Sch. 51) [147]. The simple diastereoselectivity was nearly the same, but the presence of... 

During the photocycloaddition of 88 with cyclopentene (Reaction 1), de of the major isomer 89 increased from 30% in nonpolar solvents up to 68 in a mixture of methanol and acetic acid. When prochiral enone 91 was irradia in the presence of a cyclopentene linked to the 8-phenylmenthol (Reaction the best selectivity was now obtained in nonpolar solvents. To explain this eff< it was proposed that the facial selectivity is high in every case and that diastereoselectivity depends on an s-cis s-trans ratio of the conjugated es influenced by hydrogen bonding [65]. Similar results were obtained with c... 

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. 

Steric interactions can dramatically affect regioselectivity as well. This is demonstrated by the result that cyclohexenone reacts with vinyl acetate to give exclusively the head-to-tail regioisomer (9) while 3-methylcyclohexenone produces a 1 4 mixture of the head-to-head head-to-tail isomers (10) (11) (equation 8). Additionally, 3-n-butylcyclopentenone undergoes photocycloaddition with vinyl acetate to give a 3 1 mixture of head-to-tail head-to-head photoadducts while 1-acetoxy-l-hexene gives rise to exclu-... 

A recent application of the furan-carbonyl photocycloaddition involved the synthesis of the mycotoxin asteltoxin (147)." Scheme 16 shows the synthetic procedure that began with the photoaddition of 3,4-dimethylfuran and p-benzyloxypropanal to furnish photoaldol (148), which was epoxidized with MCPBA to afford the functionalized product (149) in 50% overall yield. Hydrolysis (THF, 3N HCl) provided the monocyclic hemiacetal which was protected as its hydrazone (150). Chelation-controlled addition of ethylmagnesium bromide to the latent a-hydroxy aldehyde (150) and acetonide formation produced compound (151), which was transformed through routine operations to aldehyde (152). Chelation-controlled addition of the lithium salt of pentadienyl sulfoxide (153) followed by double 2,3-sigma-tropic rearrangement provided (154) as a 3 1 mixture of isomers (Scheme 17). Acid-catalyzed cyclization of (154) (CSA/CH2CI2) gave the bicyclic acetal (155), which was transformed in several steps to ( )-asteltoxin (147). ... 

The photocycloaddition of alkenes to the enol acetate (30) affords the adducts (31) in an example of the well-established de Mayo reaction. ... 

The photoaddition of methyl acrylate to pyridones (49) gave the three [2 + 2] cycloaddition products (50), (51), and (52).Similar observations have been reported previously.A patent has been lodged which deals with the photoad-dition of alkenes (RCH=CH2 R = H, CN, or MeC02CH2) to the pyridones (53) to yield the adducts (54) and (55). The photocycloaddition of vinyl acetate to the pyridinones (56) affords the head-to-tail adducts (57) preferentially. ... 

Wender and co-workers have continued their elegant use of the meta photocycloaddition of ethylenes to arenes as the key step in the synthesis of several naturally occurring compounds. The major product from irradiation of benzene and vinyl acetate is the 1-endo acetate of (36), and using this as the starting material, the total synthesis of the ant defensive secretion, isoiridomyrmecin (50), has been accomplished in seven further steps." There... 

---