Hydrogen shift, photocyclization

The photocyclization of enamides to quinolines or isoquinolines has become an important reaction in the synthesis of alkaloids 219,358). It has recently been applied in the preparation of the isoquinoline alkaloid polycarpine 359). The principle of the reaction is demonstrated in the preparation of dihydroquinolines 360> (3.39) and of spirocyclohexaneisoquinoline derivatives (3.40) 361K In each case the electrocyclic ring closure product undergoes a subsequent 1,5-hydrogen shift. 

Enamides 163 undergo photochemical conrotatory six-electron electrocyclic reactions to yield the dihydro intermediate 164, which in turn yields the fraws-fused cyclic product 165 (equation 105) by a (l,5)-suprafacial hydrogen shift. Several natural product syntheses like that of benzylisoquinoline and indole type alkaloids can be achieved by this type of photocyclization (equations 106163, 107164, 108165 and 109166). 

The reaction mechanism of photocyclization of aryl vinyl ethers was derived from results obtained by means of flash photolysis. The ground state intermediate rearranges by mono-or bi-molecular 1,4-hydrogen shifts to yield the products (Scheme 62) (81JOC978). The photocyclization of 2-aryloxyenones was used in the total synthesis of ( )-lycoramine (77JA8065). The formation of dihydrobenzo[6 ]furans by radical cyclization from o-allenyl-oxyarenediazonium salts with tri-n-butyltin(IV) hydride was successful (81CC136). 

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. 

Scheme 24 Absolute asymmetric photocyclization of a succinimide derivative involving a 1,5-hydrogen shift.

N,N-Dibenzylamino)-2-phenylpent-1-ene similarly undergoes photocyclization via a 1,7-hydrogen shift. An electron transfer mechanism may also be implicated in the photoreactions of the... 

Grellmann and colleagues present kinetic evidence that the non-oxidative photocyclization of Waryl enamines to indolines involves a tunneling contribution to the sigmat-ropic hydrogen shift. They conclude that only a [1,4] sigmatropic shift takes place, and it is very unlikely that [1,2] hydrogen shifts play a substantial role in the reaction (Scheme 7) [66]. 

The most striking photocyclization of a 1,3-cyclohexadiene is one which occurs with concomitant shift of a hydrogen atom. Irradiation of 1,2,3,4,-5-pentaphenyl-l,3-cyclohexadiene (Formula 359) in the absence of oxygen in benzene solution gives l,2,3,5,6-pentaphenylbicyclo[3.1.0]-hex-2-ene (Formula 360) (158). 

This remarkable reaction requires the shift of a hydrogen atom prior to cyclization and appears to be closely related to the photocyclization rearrangement recently observed in alkyl tropyl ethers (see Sec. IVD,3). 

The side reactions of l,8a-DHNs were due to the 8a-hydrogen. Replacement of the 8a-hydrogen by a methyl group can eliminate the //-shift reactions and prevent the thermal disrotatory ring opening reaction. However, the photocyclization and photo-opening reaction are little affected, based on their conrotatory reaction... 

Related to the stilbene cyclization is the photoreaction of 2-vinylbiphenyls to give 9,10-dihydrophenanthrenes. The photocyclization of (141) and its Z-isomer is shown to be highly stereoselective on direct irradiation, but totally unselective when sensitized with benzophenone or xanthene. These results support the proposal that the singlet state undergoes conrotatory ring-closure followed by a suprafacial 1,5-shift of hydrogen, whereas the triplet-state reaction proceeds through a common intermediate, possibly a perpendicular triplet state. 

Table 135.1 shows the protonation states of some of the key residues through the primary and branched photocycle intermediates in BR. Isomerization of the chromophore creates an electrostatic environment that destabilizes the protonated Schifif base. The Schiff base donates a proton to a nearby aspartic acid residue, Asp-85 (D85). Concomitant with the protonation of Asp-85 is a release of a proton from the proton release group, collectively referred to as XH, because the process is still poorly understood. Deprotonation of XH involves the participation of Arg-82, Glu-194, Glu-204, and a hydrogen-bonded network of internal water molecules. The proton movement from the Schiff base to Asp-85 generates the M state, which is blue-shifted, because the Schiff base is unprotonated. The O state is characterized by a deprotonated leaving group and an ah-tram chromophore. The chromophore is reprotonated in the M — N transition by transfer of a proton from another nearby aspartic acid, Asp-96. 

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