Solid-state photocyclization

When 8 a is used instead of 2a for complexation with 50a, two kinds of 1 1 inclusion complexes 57 were obtained one (57a) is photoreactive and the other (57b) is photostable. Thus when a solution of 8a and an equimolar amount of 50a in benzene was kept at room temperature for 10 h, a 1 1 inclusion complex between both (57a) was obtained as colorless fine needles of mp 110 to 123 °C which upon irradiation in the solid state for 49 h gave (1 R,5S)-(+)-52a of 3.6% ee in 30% yield 13). However, recrystallization of 57a from benzene gave a different kind of 1 1 inclusion complex (57b) as colorless needles of mp 123-125 °C which is photostable. Photocyclization of 50a in 57b is probably prevented by a steric hindrance. The different behavior of 57a and 57b may be clarified in future by X-ray structural studies. 

Table 10. Solid-state photocyclization of oxoamides to p-lactams using inclusion complexation...

The most exciting enantioselective photochemical conversion of a a-oxoamide to a P-lactam has been found in the case of N,N-diisopropylbenzoylformamide (96) which gives P-lactam 97. In the photocyclization of plain 96 in the solid state, optically active P-lactam 97 of high optical purity was obtained in high chemical yield. Thus no optically active host compound is necessary for the enantioselective reaction 48>. 

An example of the use of this approach in the disrotatory photocyclization of tropolone alkyl ethers is shown in Scheme 2. Thus, irradiation of the 1 1 complex of a-tropolone alkyl ether 10a with host compound 8 in the solid state gave photoproducts 11a of 100% ee and 12a of 91% ee in 11 and 26% yields, respectively [17]. 

Single crystal-to-single crystal reactions are quite rare in solid-state organic photochemistry, and we were fortunate to discover a second example in the Yang photocyclization of the 1-phenylethylamine salt of 2-methyl-2-benzoyl-p-carboxylic acid 39 [37]. 

It is important to mention again at this point that a general feature of the solid-state ionic chiral auxiliary approach to asymmetric synthesis is that not all chiral auxiliaries lead to high enantiomeric excesses. A case in point is found in the work of Natarajan et al. on the a-oxoamide-containing salts 43 (Scheme 10) [29]. Like the nonionic a-oxoamides discussed previously (Sect. 2.2), these compounds undergo photocyclization to p-lactam derivatives, and while the prolinamide salt behaves perfectly, leading to p-lactam 44 in 99% ee at 99% conversion, the corresponding 1-phenylethylamine salt affords nearly racemic photoproduct (3% ee at 99% conversion). The reason for this difference is... 

Leibovitch M, Olovsson G, Scheffer JR, Trotter J (1998) An investigation of the Yang photocyclization reaction in the solid state asymmetric induction studies and crystal strac-ture-reactivity relationship. J Am Chem Soc 120 12755-12769... 

An example is the photopolymerization of 2,5-distyrylpyrazine (DSP) (Fig. 17), with polymerization occurring via intermolecular [2-1-2] photocyclization reactions at each end of the monomer molecule. Although this reaction is regarded as a classic solid-state reaction, having been studied extensively around 40 years ago [121,122], structure determination of the polymeric product phase was only carried... 

In the crystal structure of the polymer phase (Fig. 17a), the polymer chains are aligned along the c-axis and the distance (3.71 A) between the centres of adjacent cyclobutane and pyrazine rings corresponds to half the c-axis repeat of the unit cell. For comparison between the monomer and polymer structures, an overlay plot of these structures is shown in Fig. 17b. It is clear that the solid-state reaction is associated with only very small atomic displacements at the site of the [2-1-2] photocyclization reaction (the displacement of the carbon atoms of the C=C double bonds of monomer molecules on forming the cyclobutane ring of the polymer is only ca. 0.8 A for one pair of carbon atoms and ca. 1.6 A for the other pair). Such small displacements are completely in accord with the assignment of this solid-state reaction as a topochemical transformation [124—127] (in which the crystal structure of the reactant monomer phase imposes geometric control on the pathway of the... 

Solid state photocyclization of 11 gave optically active pyrrolidinylthietane 12 in high yield <98CC2315>. 

Kohmoto et al. examined the photocyclization of /V-cinnamoyl- l -naph-thamides (274a-f) in benzene solution and in the solid state [295] (Scheme 77). Intramolecular (2tt + 2tt) and (2tt + 4tt) photocycloaddition of styryl group to the naphthalene ring was observed in benzene solution, whereas 275a-c were also obtained in the solid state. 

Intramolecular [2 + 2] photocyclization reactions of 2- /V-(2-propcnyl)amino]cy-clohex-2-enones (67) are also controlled enantioselectively by carrying out irradiation in inclusion complex with a chiral host compound. When inclusion crystals of 67 with 12 are irradiated in the solid state, optically active 9-azatricyclo[5.2.1.0]-decan-2-ones (68) were obtained in the chemical and optical yields indicated in Table 3 [30],... 

Optically pure P-lactam derivatives can also be prepared by an enantioselective photocyclization reaction of 2-pyridone in its inclusion complex with a chiral host. For example, irradiation of the 1 1 inclusion complex of 1 and 4-methoxy-/V-inethyl-2-pyridone (33) in the solid state gave (—)-34 of 100% ee... 

An asymmetric photocyclization of a-oxoamide 440 in solid state afforded azetidine-2-one 441 (Equation 176) <1996J(P2)61>. The substrate with a chloro group on either ortho- or para-position of the phenyl ring, however, afforded a racemate. Photocyclization of the phenylglyoxamides 442 of enantiomerically pure a-amino acid methyl esters produced azetidin-2-ones 443 and 444 in moderate to high diastereoselectivity, with the m-isomer as the major component (Equation 177) <2002SL131>. 

Acrylanilides also undergo this photoinduced process the reaction can occur either in the solid state or in aqueous suspension. In this way, optically active photoproducts can be obtained by irradiating prochiral substrates in the presence of optically active partners (1 1 complexes) (see Scheme 9.27). The substrate is highly oriented and immobilized in the chiral environment. Although photocyclization in the solid state takes a long time (close to 150 h), the photoreaction of a powdered complex in a water suspension containing sodium alkylsulfate as a surfactant proceeds more efficiently (less than 50h) [40],... 

Accumulation of the product may increase the rigidity of the medium, diminish the rate of the reaction, and ultimately limit the chemical yield of a solid-state reaction. In a recent study on the photocyclization of three chloro-substituted a-oxoamides (57-59, Scheme 36) by Hashizume et al. it was speculated that limited chemical yields may be attributed to increased internal strain caused by the... 

Highly enantioselective photocyclization of l-alkyl-2-pyridones, in the solid state, to P-lactams 29 has been achieved in inclusion crystals with optically active host compounds <02OL3255>. 

The 4-(3 -butenyl)-2,5-cyclohexadien-l-one derivative 8 functionalized with a chiral substituent group produced two types of polymorphic crystals, the a- and p-forms. Solid-state irradiation of the a-crystal caused [2 + 2] photocyclization to give 10 in 80% diastereomeric excess at 60% conversion (Scheme 1) [38]. In contrast, photolysis of the (3-crystals afforded almost complete reversal of the sense of diastereoselection resulting in the formation of 9 in 90% de at very low conversion. Photolysis of 8 in benzene solution resulted in low diastereodifferentiation. 

The host-guest and ionic chiral auxiliary approaches have been most intensively applied for solid-state asymmetric induction. A number of achiral organic compounds could be converted into chiral compounds in high enantioselectivities. However, all the photoreactions in themselves are well-known intramolecular photoreactions photocyclization, [2 + 2] photocyclization, Norrish type II photo-cyclization, di-ir-methane photorearrangement and photoisomerization. New types of asymmetric photoreactions have never been reported. 

Photocyclization of acrylanilide 21 to 3,4-dihydroquinolin-2(l//)-one 22 was applied in alkaloid synthesis, but enantiocontrol was unsuccessful in solution [46]. Solid-state photolysis of 21 in the 1 1 inclusion complexes with optically active host compounds 6a-c gave 22 in almost perfect optical yields (Scheme 5) [34,47]. X-ray crystallographic analysis revealed that the configuration of the photocyclization products depended on slightly different lattice structures, which were controlled by the host molecules. 

Tropolone ethers have served as useful probes of asymmetric induction using several different supramolecular approaches [49]. Solid-state photolysis of 1 1 host-guest complexes of tropolone methyl ether 25 with (R,R)-( — )-4 caused disrotatory [2 + 2] photocyclization to 26 followed by transformation to afford... 

Solid-state photolysis of host-guest complexes of 2-alkylpyridones 34 with the optically active host compounds 4, 6a, 7a,b caused disrotatory [2 4- 2] photocyclization to give chiral bicyclic p-lactams (+) or (— )-35 with high enantiosel ectivities (Scheme 8) [54]. For instance, the 1 1 complex of 2-methylpyridone 34a with (/ ,/ )-(— )-6a produced the optically pure P-lactam (+ )-35a in 93% chemical yield at 15% conversion. 

Optically active (3-lactams, such as penicillin derivatives, are important antibiotics. Since the reports of Norrish type II photocyclization of a-oxoamides to racemic (3-lactams in solution [69,70] and in the solid state [71], enantiocontrol of the photocyclization has been intensively studied by using supramolecular aproaches. First, host-guest complexes with deoxycholic acid 1 and cyclodextrin 2 as host compounds have been applied, but the transformation of a-oxoamides... 

Achiral 3,4-bis(diphenylmethylene)-A-methylsuccinimide 102 crystallized in three polymorphic forms, one of which was chiral in space group P2X. Irradiation of the enantiomorphous crystal (+ )-102 gave the optically active photocyclization product ( + )-103 in 64% ee (Scheme 24) [95]. This enantioselective photoconversion consists of two steps, a conrotatory ring closure and a 1,5-hydrogen shift. The latter sigmatropic reaction occurs in the solid state in a suprafacial manner. 

Ito Y, Matsuura T. A simple method to estimate the approximate solid state quantum yield for photodimerization of trans-cinnamic acid. J Photochem Photobiol 1989 50 141-145. Ito Y, Matsuura T, Fukuyama K. Efficiency for solid-state photocyclization of 2,4,6-triisopropylbenzophenones. Tetrahedron Lett 1988 29 3087-3090. 

---