Synthesis electrocyclic reactions

Thermal and photochemical electrocyclic reactions are particularly useful in the synthesis of alkaloids (W. Oppolzer, 1973,1978 B K. Wiesner, 1968). A high degree of regio- and stereoselectivity can be reached, if cyclic olefin or enamine components are used in ene reactions or photochemical [2 + 2]cycloadditions. 

Synthesis of [d]-annelated indoles by thermal electrocyclic reactions 95MI7. 

Although the above-mentioned electrocyclization reactions were well studied prior to the discovery of the endiandric acids, their utilization in the total synthesis of complex molecules had not been demonstrated. The endiandric acids, therefore, offered an irresistible opportunity to explore the utility of electrocyclization reactions in synthesis. The successful studies disclosed below demonstrate that these reactions can provide concise solutions to the challenge presented by complex polycyclic frameworks. 

Through a display of a series of electrocyclization reactions, the Nicolaou group demonstrated the biomimetic , one-step synthesis of the endiandric acids involving the cascade of reactions proposed by Black. The polyunsaturated compounds 37 and 38 (Scheme 7) were designed for their relative stability and potential to serve as... 

For reviews for pericyclic ring-closures, see (a) Marvell EN (1980) Thermal electrocyclic reactions. Academic, New York (b) Okamura WH, de Lera AR (1991) In Trost BM, Fleming I, Paquette LA (eds) Comprehensive organic synthesis, vol. 5. Pergamo, New York, pp 699-750... 

Surprisingly little is known about isomerization reactions of [4]radialenes. 5,6,7,8-Tetravinyl[4]radialene 127 is certainly a unique case since it appears to be in equilibrium with its precursors in synthesis, 125 and 126, by electrocyclic reactions (equation 8). As 127 has not been isolated in pure form and is unstable with respect to polymerization, no details on this possible equilibrium are known79. 

The electrocyclic reaction of divinylindoles to functionalized carbazole derivatives has emerged as an efficient method for the synthesis of a diverse range of carbazole derivatives. This reaction has been achieved at high temperatures in the presence of palladium on charcoal or DDQ. The palladium catalyst or DDQ act as dehydrogenating agent (534,535) (Scheme 5.19). 

A new benzannulation methodology was developed in order to overcome the limitations of electrocyclic ring closure of divinylindoles. The cyclization is achieved via an allene-mediated electrocyclic reaction of 2,3-difunctionalized indoles. This method is more efficient for the synthesis of highly substituted 2-methyl carbazole alkaloids (559). The 3-alkenyl-2-propargylindole 557, a precursor for the allene intermediate, was prepared from 2-formylindole over several steps using simple functional group transformations (536,537) (Scheme 5.20). 

Hibino et al. reported a formal synthesis of murrayaquinone A (107) starting from 2-chloro-3-formylindole (891) by an allene-mediated electrocyclic reaction involving the indole 2,3-bond. The 4-hydroxy-3-methylcarbazole (858), a known precursor for murrayaquinone A (107), and required for this formal synthesis was obtained in seven steps, and 26% overall yield, starting from the 2-chloro-3-formylindole (891) (636,637) (Scheme 5.114). 

Hibino et al. reported the total synthesis of carbazomycin G (269) by the regioselective addition of methyllithium onto 3-methoxy-2-methylcarbazole-l,4-quinone (941) (653). The required immediate precursor of carbazomycin G, carbazole-l,4-quinone 941, was obtained from 3-(2-methoxyethenyl)-N-(phenylsul-fonyDindole (986). The benzannulation involves an allene-mediated electrocyclic reaction of a 67t-electron system generated from the 2-propargylindole 989, which was derived from the 3-vinylindole 986 in three steps. 

In the same year, Hibino et al. reported a total synthesis of furostifoline (224) employing a new type of electrocyclic reaction (636). This cyclization proceeds through a 2-alkenyl-3-allenylindole intermediate, which is derived from 2-(fur-3-yl)-3-propargyUndole 1128. Compound 1128 was prepared starting from 2-chloroindole-3-carbaldehyde (891), furan-3-boronic acid (1124), and ethynylmagnesium bromide. 

Thus in the N-silyl substituted series, 17 and 18, which rearrange thermally to the corresponding diazo compounds, the stability increases through the series R=Me, Ph, i-Pr. As discussed below, these compound undergo the usual cycloaddition and electrocyclization reactions of nitrile imines and are not simply overstabilized curiosities. The usefulness in synthesis of those with P—C bonds is probably limited since these bonds are not easily broken, but products derived from those with C—Si and C—B bonds (e.g., 21 and 22) should be capable of further... 

Vasiliy Bakulev was bom in Ekaterinburg, Russia. He obtained his Ph.D. in 1979, under the guidance of Prof. Vladimir Mokrushin, on the synthesis of imidazole derivatives. Then he studied electrocyclic reactions of diazocompounds and azomethyneylides and, in 1990, defended the second thesis of Doctor of Science (similar to Habilitation Degree) at Moscow State University. He received a diploma of Professor in 1998. Jointly with Wim Dehaen, he published a book on the chemistry of 1,2,3-thiadiazoles in 2004. He is currently professor at the Organic Synthesis and Technology Department of the Urals State Technical University (Ekaterinburg, Russia). 

Thermal electrocyclic reactions of 1-azahexatriene systems can be used to obtain imidazo[4,5-c]pyridines (25) [95H(41)161] and the thermal cyclisation of 2-alkynylbenzene-diazonium salts (the Richter reaction) has been extended to the synthesis of pyrazolopyridazines (26) (Scheme 17) [95LA775],... 

Pyrroles, H.M.L. Davies. Synthesis of Porphyrins with Exocy-clic Rings from Cycloalkenopyrroles, T.D. Lash. Palladium-Catalyzed Coupling Reactions of Indoles, A.R. Martin and Q. Zheng. Cycloaddition Reactions of Indole Derivatives, U. Pindur. Transition-Metal Mediated Synthesis of Carbazole Derivatives, H. J. Knoiker. Synthesis of [b]-Annelated Indoles by Thermal Electrocyclic Reactions, S. Hibino and E. Sugi-no. Total Synthesis of (-) and ent (-) Duocarmycin SA, D.L. Boger. Index. I... 

The actual cyclisation stage is not as imponderable as it appears. The first step is the acid-catalysed equilibration between hydrazone 7.8 and ene hydrazine 7.10. The next step, which is irreversible, is a concerted electrocyclic reaction, forming a strong carbon-carbon bond, and breaking a weak nitrogen-nitrogen bond. The resulting imine 7.11 immediately re-aromatises by tautomerisation to aniline 7.12. Finally, acid-catalysed elimination of ammonia forms indole 7.9, reminiscent of the last step of the Knorr pyrrole synthesis (Chapter 2). 

Electrocyclic reactions are a type of pericyclic rearrangement reaction where the net result is a conversion of one Tt-bond into a G-bond (Scheme 9.16). These reactions can be either photochemically or thermally induced. Selected examples of the potential of photoinduced 6jt-electrocyclization for organic synthesis are shown below. 

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]. 

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