SYNTHESIS Photochemical cyclization

The protoberberine alkaloid, xylopinine, has been synthesized in an optically active form by Kametani et al.22 ). A key reaction in this synthesis was the photochemical cyclization of the optically active amino acid derivative 1,2,3,4-tetrahydro-6,7-dimethoxy-3-methoxycarbonyl-1 -methylene-2-veratroylisoquinoline with 1,3... 

The first synthesis of nagilactone F was carried out by Hayashi et al. [83] starting from (+)-0-methylpodocarpic acid 158 in 23 steps (2% overall yield). The main characteristics of this synthesis include the transformation of the aromatic ring into the 5-lactone ring, the a arrangement (equatorial) of the isopropyl group by photochemical cyclization, as well as the construction of the y-lactone using radical conditions (Scheme 14). 

The chemistry outlined in Scheme 24 was then put into effect catalytic hydrogenation of the tris-isoxazole (302) and recyclization with triethylamine gave a tricyclic ligand which was chelated with nickel ions to give (303). Introduction of the fourth nitrogen atom was accomplished by treatment of (303) with ammonium acetate, giving (304). Treatment with cyanide removed the nickel ion which was then replaced with zinc(II) to give (305). The reasons for this transmetallation step were two-fold firstly, zinc(II) corrins, as shown by Eschenmoser, can be readily demetallated, and this fact opens up many options later in the synthesis, but secondly, and more importantly, Eschenmoser s photochemical cyclization of seco-corrins (see Section 3.07.3.4.2.3) does not proceed with nickel complexes of seco-corrins, whereas zinc(II) seco-corrins can be cyclized in almost quantitative yield... 

In tandem with their collaboration with the Harvard group vide supra), the E.T.H. Zurich group, under Eschenmoser, was also developing a most remarkable synthesis of vitamin B12 which employed a totally different methodology, namely the photochemical cyclization of an appropriately substituted seco-corrin. The ground work had already been laid with models, and has been discussed in an earlier Section (3.07.3.4.2(//)). 

Padwa et al. <2004JOC33, 20010L1781> established a method for the synthesis of complex fused-ring thietanes by the intramolecular [2+2] photochemical cyclization of thiosuccinimide and dithiosuccinimide derivatives. In the... 

A similar synthesis of tricyclic fused-ring thietanes by photochemical cyclization of N-substituted mono- and dithioglutarimides has been reported (Equations 17 and 18) <2000H(53)2781>. The carbonyl compound 64a and thiocarbonyl derivatives 65 were obtained in moderate yields. An analogous route was used for thiosuccinimides, where the use of a dithioglutarimide derivative resulted in the formation of a bicyclic side product 65. 

The photochemical electrocyclic reaction of acrylamides represents a versatile strategy for alkaloid synthesis. Thus, (S)-pipecoline has been synthesized using the photochemical cyclization of enantiomerically pure acrylamide derivatives in the presence of NaBH4, which causes reduction of the imonium intermediate. The lactam may then easily be transformed into the desired heterocyclic compound (Scheme 9.26) [38]. 

The photochemical strategy, first applied by Ito and Tanaka in their synthesis of erybidine (1) (33), was later extended to the preparation of laurifine (5), lau-rifonine (4), and laurifinine (6). These three 2,11,12-trisubstituted dibenzazo-nines were prepared employing the photochemical cyclization of amide 16 as the key step (Scheme 3) irradiation of 16 in methanolic sodium hydroxide solution gave a mixture of 17,18, and 19 from which the major compound was separated and transformed into the above-mentioned derivatives (26). The cyclized product 18 was later used as a precursor in the synthesis of neodihydrothebaine (7) (34). 

A photochemical cyclization gave high yield of chlorins, as depicted in Scheme 7 (83CC1235). The reaction is also used for an efficient synthesis of 107a (83CC1237). 

The limitation to die widespread synthetic use of the thermal or photochemical cyclization of trienes are twofold the difficulty in preparing the starting, geometrically correct triene array and the periselec-dvity (i.e. the competition widi other reactions occurring from he same substrate). Much of the following discussion is limited to the latter topic although it must be recognized that an efficacious synthesis of... 

The known examples of the synthesis of higher-order simulated systems (exemplified by types XVI-XVn in Figure 2) involve photochemical cyclization followed by oxidation of aiene analogs of stilbenes. 

An efficient route to the synthesis of the cycloalkanones (37) involving the intramolecular photochemical cyclization of the enones (38) has been described. This yields the tricyclic... 

The cage compound (301) is formed efficiently on irradiation of the adduct (302).Irradiation of the ene dione (303) affords the cage compound (304) by a (6 + 2)-cycloaddition. The Diels-Alder adducts (305) are photochemically reactive. Irradiation of (305) affords either the cage compounds (306) by a (2+2)-cycloaddition reaction, a process favoured by the adducts (305 a,b), or the oxetanes (307). The structures (306, 307) were verified by 2L ray diffraction studies The quinone adduct (308) also undergoes photochemical cyclization to afford the cage diketone (309). This material was subjected to flash vacuum pyrolysis to yield the diketone (310) important in the synthesis of perhydroindacenes. ... 

The structure of alamarine [( )-58], a typical member of this benzopyri-doquinolizine family, was confirmed by its synthesis featuring thermal or photochemical cyclization of the enamide 134 (1,116). Chowdhury (227) synthesized isoalamarine (59) from the isomeric enamide 135 via a parallel route. For the syntheses of ( )-alangimaridine [( )-61] and alangimarine... 

Strained cage compounds can be made by intramolecular photocycloaddition of properly designed ene/enone substrates. In an interesting example from J. R. Scheffer, a ben-zoquinone derived Diels-Alder product is regioselectively transformed into a (halO cage compound. This is a more complicated version of the classical intramolecular photochemical cyclization reactions of benzoquinone derivatives (for example see B. Pandey s cage synthesis from a naphthoquinone-cyclopentadiene in Chapter 3). 

An example of a photochemical cyclization was reported by Takei et al. [92], who demonstrated the synthesis of L-pipecolinic acid (160) from an aqueous solution of L-lysine (161), as illustrated in Scheme 6.42. To achieve this photocatalytic transformation, the authors fabricated a Pyrex micro reactor in which the channel cover plate was coated with a 300nm layer of anatase Ti02 (100 nm particles), to afford a titania-coated micro reactor (TCM) the titania film was subsequently loaded with platinum (0.2 wt%), by photodeposition, to enable the TCM to be used... 

Considerable efforts have been made in the synthesis of the Strychnos angustiflora alkaloids reviewed last year. A photochemical cyclization lies at the heart of a neat synthesis " of angustidine (85a) (Scheme 13). 18,19-Dihydroangustine (85b) has been prepared from vincoside lactam tetra-... 

Only one example of this type of synthesis is reported, a photochemical cyclization of an N-(oxazinyl) /S-diketone (228) (Equation (87)) <76JCS(P1)2054>. 

The total synthesis of bonellin dimethylester (85) could be achieved by a very similar approach as for (77) including the photochemical cyclization 53c, 56). The approach to bonellin dimethylester (85) (57) developed by Montforts et al. makes use of four monopyrrolic building blocks (78), (79), (81), and (83) which were assembled together by methods from porphyrin, bile pigment, and corrin chemistry to give the macrotetracycle. 

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