Vinylogous imides

Another useful method for effecting the ring closure of the bromo- and iodoaryl enaminones 166 (Z = Br, I) featured an intramolecular electrophilic arylation process involving benzyne intermediates (127). For example, treatment of 166 (Z = Br, I) with lithium diethylamide at room temperature afforded the pyrrolophenanthridone 169. When 169 was treated with oxygen in aqueous ethanol containing potassium hydroxide, the vinylogous imide 168 was produced... 

This technique has been applied to a vinylogous imidate.454,455... 

The utility of /f-enaminones (vinylogous amides) and / -enamidones (vinylogous imides) has been successfully demonstrated in both inter- and intramolecular [2 + 2] photocycloaddition reactions. The vinylogous amide, which reacts as a /Mieteroatom substituted enone, serves as the nitrogen analogue of the enol form of a / -diketone in the de Mayo reaction24. 

Some of the earliest work on the [2 + 2] photocycloaddition chemistry of vinylogous imides was reported by Wiesner and coworkers, who described the isolation of the [2 + 2] photoaddition products resulting from the irradiation of cyclic vinylogous imides with ethyl acrylate and allene, respectively (Scheme 12)29. 

Similarly, Cantrell observed intermolecular photocycloaddition of vinylogous imide 44 with cyclopentene on irradiation through Pyrex to give cyclobutane 45 (equation 13)30. 

A key step in the synthesis of 12-epi-lycopodine reported by Wiesner and coworkers is the intramolecular [2 + 2] photocycloaddition of a vinylogous imide and an allene. Irradiation of photosubstrate 46 produced a single cyclobutane 47, in which the allene added to the vinylogous imide anti to the methyl group (Scheme 13)31. Photoadduct 47 was converted to ketal-alcohol 48 via a three-step sequence of ketalization, epoxida-tion and reduction. Hydrolysis of the ketal unmasked the /Miydroxy ketone functionality. Retro-aldol fragmentation followed by aldol closure gave hydroxyketone 49, which was readily converted to the polycyclic alkaloid 12-epi-lycopodine. 

Schell and coworkers have reported the cyclization-fragmentation chemistry of related vinylogous imides as a function of tether length (Scheme 14)32. Irradiation of the vinylogous imide 50 produced the crossed photoadduct 51, in which the iV-acetyl group... 

Irradiation of vinylogous imides 56 and 58 led to products derived from a different reaction pathway. None of the expected [2 + 2] adducts formed, but instead products 57 and 59 resulting from a photochemical ene-type reaction were isolated in good yield (Scheme 15)35. The authors proposed that hydrogen atom transfer from diradical 60 could lead to the formation of the observed product 57. 

Similar photo-Fries reactions have been reported by Schell and co workers. Irradiation of vinylogous imide 50 led not only to the formation of the crossed photoadduct 51 (as outlined in Scheme 14) but also to the formation of 137, the product of acyl group migration (equation 18)32. 

When treated with acrylic acid, bicyclic enamine 195 was converted to the tricyclic vinylogous imide 196, which was then incorporated into the synthesis of the Lycopodium alkaloid annotinine (197) as well as an annotinine degradation product (eq. 42).67... 

A novel inU olecular Diels—Alder reaction of a vinylogous imide was 8) f7"9f construction of the tricyclic core ABC (see Scheme... 

By making use of the viability of inducing intramolecular [4+2] cycloadditions using vinylogous imides as the dienophilic reactant and the application of such a process to the facile synthesis of the tricyclic ABC ring (see Scheme 18), the tetracyclic ABCE unit was constructed (see Scheme 29). The process includes an intramolecular Diels-Alder reaction followed by a novel olefin metathesis reaction to form the azocine ring... 

Wiesner carried out pioneering studies on the photocycloaddtion of vinylogous imides in the 1960s, and he first applied the intramolecular photochemical [2 + 2] enone-olefin cycloaddition reaction in natural product synthesis. In his landmark synthesis of 12-e/>i-lycopodine, compound 186 is irradiated to give a 70% yield of photoadduct 187. Protection of the ketone, epoxidation of the exocyclic double bond, and reduction of the epoxide give ketal alcohol 188. Deprotection of the ketal and spontaneous refro-aldol fragmentation lead to the diketone 190. Of note is that the bond cleaved in this retro-a do pathway (i.e., 189 to 190) is different from that of typical de Mayo reactions. Diketone 190 transforms to the tetracyclic alcohol 191 via aldol reaction, and this alcohol is converted to 12-e/7/-lycopodine in four steps. 

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