Photochemical cyclizations, precursor synthesis

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). 

Photochemical aromatic substitution initiated by a reductive step as in SRN1 reactions can be used for the synthesis of cephalotaxinone (15). The corresponding iodoketone precursor cyclizes in liquid ammonia under photolysis [15]. 

R = H) in 20% yield. Compound (111 R = OMe, R == H) has also been synthesized by a conventional Pschorr cyclization route.The photochemical oxidation of glaucine to 7-oxoglaucine has been reported. Photochemical synthesis of the unusual aporphine alkaloid thalphenine (113 N-Mel) has been achieved. Irradiation of (114) under basic conditions gave directly (113), presumably via the intermediate quinone methide (115), which results from the initially formed aporphine precursor by elimination of the elements of methanol. Quaternization of (113) provided ( )-thalphenine (113 A/-Mel), whose Hofmann elimination gave the alkaloid thaliglucine (93 R = H2). 

Unimolecular cyclization reactions and both nucleophilic and photochemical addition of the O—O unit to appropriate precursors constitute the primary routes which have been reported for the synthesis of 1,2-dioxocins from acyclic precursors. Barton-type cyclization of appropriately-substituted organic peroxides affords low (52) (Equation (23)) <83LA6io> to modest (54) (Equation (24)) <83LA624> yields of cyclic products. 

Whilst the above results demonstrate the clear potential of stilbenoid compounds for the photochemical synthesis of large aromatic systems, the scope has not yet been exhausted. Indeed, the ready synthetic availability of the stilbene precursors, together with the tolerance to a large selection of substituents and mild reaction conditions, make this approach particularly attractive for - and complementary to - other cyclization strategies such as the Lewis acid-mediated SchoU reaction, which is compatible with only a few classes of functional groups (vide supra). 

A chiral menthol auxiliary has been utilized by Hoffmann and coworkers for the radical addition/cyclization reaction of N,N-dimethylaniline 242 with 5R)-menthyloxyfuran-2(5H)-one 245 using photochemical electron transfer (PET). The reaction led to 246 and 247 with 44% yield and 3.3 1 diastereoselectivity [77, 78] (Scheme 5.52). A modified menthol auxiliary was utilized for the asymmetric synthesis of a chiral precursor to the natural terpenoid (+)-triptocallol by Yang and coworkers [79]. The reaction was performed under oxidative radical conditions mediated by l.Oequiv of Yb(OTf)3 and 2.2equiv of Mn(0Ac)3-2H20 Mn(OAc)3. Reasonable yields of 55-72% and a diastereoselectivity of 24.2 1-2.8 1 were... 

Synthesis of Precursors for Photochemical and Cationic Cyclizations. Allyl(2-chloroethyl)dimethylsilane (4) was converted to thiol 15 by nucleophilic displacement with thiolacetic acid and treatment of the resultant thioacetate with ammonia. UV irradiation of 15 gave exclusively the 7-endo cyclization product 16 (eq 8). ... 

The enediyne structure in anticancer drugs, that act via DNA cleavage, is caused by a diradical formed in cyclo-aromatization. Thus a triggering mechanism was required to initiate the cyclization of stable precursors under physiological conditions (temperature about 37°C). Photochemical triggering is one approach used for this purpose. In some cases, it was achieved by photochemical synthesis of reactive enediynes that then readily undergo cyclo-aromatization [244]. 

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