Witkop photocyclization

The first method for the preparation of tetrahydroazocino[4,5,6-cd]indoles was reported in 1966. In succeeding years, this reaction came to be known as the Witkop photocyclization. 

In succeeding years, the Witkop photocyclization has been widely used for the synthesis of similar compounds. For example, the dichloroacetyl derivative of tryptophane in the presence of sodium azide under the conditions of photocyclization (93JA813) produces 7-azidoazocinoindole 65 in 49% yield (Scheme 20). 

An interesting new synthesis " of the tetracyclic base (150) (Scheme 26), which involves as key stages the y-alkylation of an a,/3-unsaturated amide and a Witkop photocyclization, affords an alternative route to the synthesis of tubifoline, tubifolidine, and condyfoline, previously obtained from (150) by Harley-Mason and co-workers. 

Scheme 2. The initial discovery of the Witkop photocyclization (a) and subsequent applications in natural product total synthesis (b,c).

Scheme 13.11 Total syntheses of the indole alkaloids ( )-decursivine (81) by using a Witkop photocyclization/elimination cascade sequence.

In 2011, the group of Jia described a short and efficient total synthesis of ( )-decursivine (81) by employing a cascade Witkop photocyclization/elimination/ cyclization sequence (Scheme 13.11) [13], The synthesis just went through five steps in 19% overall yield, with no protection groups used. Furthermore, this cascade reaction could also be applied to the asymmetric total synthesis of (-)-decursivines and their analogs. 

Qin, H., Xu, Z., Cui, Y, Jia, Y. (2011). Total Synthesis Of ( )-Decursivine And ( )-Serotobenine a witkop photocyclization/elimination/O-Michael addition cascade approach. Angewandte Chemie International Edition, 50, 4447-4449. 

Many applications of the Witkop photocyclization of iV-chloroacetylamides have been reported. The synthesis of 7-oxodesethylcatharanthine (118) in 55% yield, by irradiation of the N-chloroacetylamide (117) in methanol, illustrates this. "... 

Anderson and Lavton in 1977 described vinyl modification of the Witkop cyclization to give azecino[4,5,6-cd]indole 79 from tryptophane 78. But later it was proven that the product was, indeed, azocino[4,5,6-cd]indole 80 (99TL8443). The same photocyclization has been used for trichlorobutenamide 81 with the resulting formation of azocinoindole 82 instead of the expected 83 (Scheme 24). 

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