6n-Electrocyclizations

The proposed mechanism for the Conrad-Limpach reaction is shown below. Condensation of an aniline with a 3-keto-ester (i.e., ethyl acetoacetate 5) with loss of water provides enamino-ester 6. Enolization furnishes 10 which undergoes thermal cyclization, analogous to the Gould-Jacobs reaction, via 6n electrocyclization to yield intermediate 11. Compound 11 suffers loss of alcohol followed by tautomerization to give 4-hydroxy-2-methylquinoline 7. An alternative to the proposed formation of 10 is ejection of alcohol from 6 furnishing ketene 13, which then undergoes 671 electrocyclization to provide 12. 

This information coupled with the proposed mechanism of the Conrad-Limpach reaction, reasonably lead to the below proposed mechanisms. Conjugate addition of aniline and elimination of alcohol provides the P-anilinoacrylate 14, which upon heating to 180-320 °C gives species, like 34a,b, which undergo 6n-electrocyclization to 35 or 36, respectively. Loss of ethanol from 36 gives 35 and tautomerization provides 4-... 

Relatively few examples of photochemically induced 6n -electrocyclizations of azahexa-l,3,5-trienes to azacyclohexa-1,3-dienes have been documented the reverse process involving ring cleavage, however, is more common. The formation of azalumazin-7-ones 19 from triazahexatrienes 20 under oxidative conditions can be regarded as an example of such a process,18 but... 

The 877-electrocyclization of carbonyl ylides of type B, e.g., the ylide derived from oxirane 145, was less favored than the 6n electrocyclization to yield a mixture of three compounds 146 and isomers 147 (in a ratio of 3 7). The annulated vinylfuran derivative 147 formed as mixture of isomers (cis-trans 4 3) while the stereochemistry of the single isomer of 146 has been established by X-ray analysis of the Diels-Alder adduct (Scheme 44) [81TLC194953 85CB4035]. 

Examples of photochemically induced 6n electrocyclizations in oxygen-containing systems are relatively rare. 2//-Phenanthro[9,10-/>]-pyran-4-carboxamides (16), for example, have been obtained in this way by irradiation of dienones (17). Similarly, the a-pyran (18) is formed on irradiation of E)-P- onone (19) a triplet excited state is believed to be involved and the reaction proceeds via the Z-isomer (20). The reverse process involving ring opening is more common and can lead to a wide variety of photochemically derived products. Thus, the products of irradiation of 2,2-dimethylchromene... 

A 6n electrocyclic closure could be implicated in the photocyclisation reaction reported for the N-amino pyridinium ion (257) and some of its ring substituted derivatives to give (258). This type of reactivity was also seen for compound (233). A summary of the previously published work and of new results for the 67t photocyclisation of photochromic ethylenes substituted by derivatives of cyclopentadiene anion and pyridinium cation has appeared.The basic skeleton involved in the rearrangement is shown in structure (259) which is in photochemical equilibrium with (260). 

The first example of a chiral Bronsted acid, (154), that efficiently catalyzed asymmetric 6n electrocyclization of a,j8-unsaturated hydrazones (194) to pyrazolines (195) in high yields and enantioselectivities has been presented by List and co-workers (Scheme 54)7 ... 

Smith, et al. developed an organocatalyzed 6n electrocyclization of benzaldi-mines, as precursors to 2-aza-pentadienyl anions, prepared in situ from anilines 248 and aldehydes 249, to give functionalized indolines in high yields and enantioselectivities, Scheme 3.80 [101],... 

Reduction-triggered pericyclic reaction has been used for the biomimetic total synthesis of endiandric acids A-G [72]. Endiandric acids are polycychc natural products isolated from the Australian plant Endiandra introrsa and exist naturally as a racemic mixture which is found to have very high antibacterial effect [73]. In 1980, Black and coworkers [74] proposed a hypothesis that these polycyclic systems are formed in nature by a series of electrocycUzation reactions. On the basis of this hypothesis, Nicolaou et al. [72c] in 1982 reported an excellent domino reduction/electrocyclization process for the synthesis of endiandric acid A 127 (Scheme 9.25). Selective hydrogenation using a Lindlar catalyst of diacetylenic diol 123 afforded the bicyclic diol 126. The reaction presumably proceeds via polyene 124, which then undergoes a spontaneous 8 [i-electrocyclization to give 125. It follows a second 6n-electrocyclization to afford bicyclic 126, which is further converted to endiandric acid A 127. 

Scheme 14.40 Total synthesis of shimalactones A and B (260 and 261) by Trauner and coworkers applying a domino Stille/8n/6n-electrocyclization reaction.

Scheme 5 Synthesis of echinochrome A a typical example for An-6n electrocyclic ring opening and ring closure [67]...

A synthesis of bicyclo[5.3.0]decatrienes through a Rh(I)-catalysed cycloisomerization of 3-acyloxy-4-ene-l,9-diynes has been reported " to proceed by [l,2]-acyloxy migration, 6n electrocyclization, migratory insertion, and reductive elimination. The overall process viewed as a intramolecular 5 -I- 2-cycloaddition with concomitant [l,2]-acyloxy migration (Scheme 146). 

Scheme 8.63 The Heck reaction/6n-electrocyclization cascades and its application in the synthesis of modified steroids [240, 393].

More recently, alkaloid derivatives have also found application in other transformations such as electrocyclization reactions. For instance. Smith and co-workers have shown that treatment of benzaldimine 101 with 10 mol% of cin-chonidinium chloride 102 in a biphasic system of aqueous potassium carbonate and toluene gives cyclized product 103 in 99% yield and 97% ee. The sense of stereoinduction within this 6n electrocyclization (as represented by 104) was tentatively rationalized using a modification of the... 

Conformationally constrained bispropargyl sulfones with an ort/io-alkenyl moiety under basic condition undergo isomerization to monoallene followed by a 6n-electrocyclization. Further isomerization and 6a -electrocyclization has been reported to result in bis-naphthyl sulfones (Scheme 40). ... 

Early in 1992, Negishi et al. reported a palladium-catalyzed cascade involving alkynes toward benzene derivatives [38], Recently, Blond et al. reported a palladium-catalyzed cascade reaction toward strained aromatic polycycles 100 [39] (Scheme 6.22). Bromoenediynes 98 undergo A-exo-dig cyclocarbopalladation and subsequent 5-exo-dig cyclization to afford the vinylpalladium intermediate 99, which possibly undergoes a 6n-electrocyclization and a syn 3-H elimination to furnish the products observed. 

The mechanism of the dearomatization-cyclization of aromatic amides takes place by initial lithiation at the ortho position of the aromatic ring. This species is in equilibrium with the more stable a-amide lithiated compound, which forms the final product by means of a 6n electrocyclic ring closure. 

M, Es-Samti H. A thermal 6n electrocyclization strategy towards taiwaniaquinoids. First enantiospeciUc synthesis of (—)-taiwaniaquinone G. J. Chem. Soc., Chem. Commun. 2009 592-594. 

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