Reduction Reductive photocyclization

Acyl-2-phenyloxazole derivatives undergo a reductive photocyclization in the presence of sodium borohydride to generate a bicychc oxazoline with a cis-fused pyridinone ring 307. The stereochemistry of the product is consistent with hydride attack from the less hindered surface of the cyclic intermediate 306. The oxazoline containing pyridinone is a key intermediate used for the synthesis of pseudodisto-mins 308 (Scheme 8.85, p. 415). ° ... 

The course of the reductive photocyclization of enamines by irradiation in the presence of sodium borohydride depends on the nature of substituents. Thus the AT-methyl-S-phenyl compound 46 yields a mixture of the pyrrolidinone 47, the piperidinone 48 and the tricyclic compound 49, whereas the dimethyl analogue 50 gives the piperidinone 51 as a mixture of Z- and -isomers. The cyclopentene derivative 52 affords the spiro-pyrrolidinone 53, together with the cyclopentapiperidinone 54, the naphthylthio group being eliminated (Scheme 2)50. 

Reductive photocyclization of the enamide 261 by irradiating a methanolic solution containing sodium borohydride results in a mixture of four products the hexahydrophe-nanthridone 262, two geometrically isomeric octahydrophenanthridones, 263 and 264, and the structurally isomeric octahydrophenanthridone 265 (equation 111)135. 

In the presence of metal hydride, the enamide can undergo reductive photocyclization to give the dihydrolactam in good yield. 

Furthermore, the chiral metal hydride complex, which is readily prepared from a metal hydride and chiral amine or amino alcohol, has been successfully applied to reductive photocyclization, thus allowing visualization of asymmetric photocyclization (16). 

The reaction course of the reductive photocyclization of enamides in Scheme 17 was firmly established by the experiments using deuterated reagents (75). When enamide 14 was irradiated in the presence of sodium borodeuteride in acetonitrile-methanol (10 1) solution, the isolated product 15 in 93% yield was deuterated at the 3 position, whereas irradiation in the presence of sodium borohydride in acetonitrile-deuterium methoxide solution afforded lactam 16, deuterated in the benzene ring as shown in Scheme 18 (55). 

So far, reductive photocyclization has been successfully applied to the synthesis of yohimbine-type compounds (54), benzo[/]quinolines, and ergot alkaloids including lysergic acid (55-57) (Scheme 19). 

Discovery of reductive photocyclization of enamides has certainly increased its importance as a general and useful synthetic tool. 

Irradiation of enamides in the presence of a hydride (e.g., sodium borohy-dride) in a solution containing a protic solvent such as methanol, brought about reductive photocyclization (15,54-57). However, it is assumed that irradiation in the presence of aprotic solvent affords the photocyclized product (17) identical to that formed by irradiation under nonoxidative conditions according to the route suggested in Scheme 20. 

Furthermore, an asymmetric synthesis of natural xylopinine (20) by the route involving reductive photocyclization was successfully accomplished (16). Independently, Kametani et al. reported another asymmetric total synthesis of natural xylopinine via the route involving a diastereo-differen-tiated photocyclization of the chiral enamide (19) under nonoxidative conditions (66). Therefore, it is now established that enamide photocyclization is a reaction capable of not only undergoing a wide variety of cycliza-tions under various conditions but also having a high quality (Scheme 22). 

Reductive photocyclization of the enamide 18 in ether-ethanol solution in the presence of an excessive amount of sodium borohydride afforded two... 

On the assumption that asymmetric reduction of an intermediate by a chiral metal hydride complex could occur during the course of photocycli-zation of the enamide 133, as exemplified by reductive photocyclization, Ninomiya et al. (16) have undertaken and completed the photochemical asymmetric synthesis of (—)-xylopinine. 

Successful berbine synthesis summarized in Section IV,C prompted Nin-omiya s group (25,26,117,118) to extend enamide photocyclization to har-malane, therefore giving rise to a novel and facile synthesis of polycyclic heterocycles such as the yohimbine group of compounds. Before reductive photocyclization was introduced, the use of nonoxidative photocyclization with indole alkaloids was limited to simple systems and those possessing a large degree of aromaticity. 

Depyrrole analogs of clavines were readily synthesized by applying reductive photocyclization of the enamides of acryloyl and furoylenamine types, 229 and 233 (55,56). Irradiation of the enamide 229, prepared from 2-tetra-lonimine and methacryloyl chloride in the presence of triethylamine, under nonoxidative conditions, afforded the lactams 230 and 225 in yields of 45 and 10%, respectively. Their reductive photocyclization in the presence of sodium borohydride at a low temperature of 4-5°C led to the formation of... 

Costaclavine, Epicostaclavine, and Festuclavine. In the period before introduction of reductive photocyclization in 1981, Ninomiya et al. (128,129) had synthesized three epimeric 6,8-dimethylergolines costaclavine (247), epicostaclavine (248), and festuclavine (249) via the lactam that was prepared by the reaction of the tricyclic imine 242 with methacryloyl chloride or methacrylamide. 

Epicostaclavine (248) and pyroclavine (250) were also synthesized by applying reductive photocyclization of the enamide (243) as shown in Scheme 91 (53). 

Lysergic Acid. Based on the results of the synthetic route using benzo[/]quinoline derivatives (55,56), Ninomiya et al. (57) applied reductive photocyclization to the enamide 251, prepared from the tricyclic imine 242 and 3-furoyl chloride. 

Reductive photocyclization of the enamide 251 afforded a mixture of two hydrogenated lactams 252a and b in 81% combined yield as a mixture of two... 

Novel synthetic applications of the photocyclization of enamides have been reported. Preparation of the fused quinolone (23) from the enaraide (24) was achieved by photocyclization and subsequent elimination of a suitably positioned methoxyl group Reductive photocyclization of enamides, usually carried out in the presence of sodium borohydride, is of particular value in the synthesis of alkaloids. Cyclization of the enamide (25) to the... 

Reductive photocyclization of the enamide, derived [12] from a tricyclic ketone followed by ring opening of the resulting dihydrofuran derivative... 

Reductive photocyclization of the enamide followed [15] by glycol formation and oxidative cleavage of the dihydrofuran ring... 

As an unavoidable situation we faced from smooth application of enamide photocyclization to alkaloid synthesis, we have investigated a new developement in enamide photocyclization and found a very efficient and most useful synthetic methodology in what we called " reductive photocyclization ". 

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