Domino cyclization

Scheme 1.8. Domino cyclization/rearrangements via iminium ions.

Scheme 1.24. Lewis acid-catalyzed cationic domino cyclization to give bicyclo[2.2.1]heptane derivatives.

Scheme 1.28. Acyliminium ion-initiated domino cyclization in the synthesis of azasteroids.

As mentioned earlier, the McDonald group was able to extend their epoxide-domino-cyclization strategy to 1,5,9-triepoxides [10]. Indeed, they were successful in converting precursor 1-143 into the tricyclic product 1-146 in 52 % yield after hydrolysis (Scheme 1.36) [41]. As a possible mechanism of this polyoxacyclization it can be assumed that, after activation of the terminal epoxide by BF3, a sequence of intramolecular nucleophilic substitutions by the other epoxide oxygens takes place, which is induced by a nucleophilic attack of the carbonate oxygen, as indicated in 1-144 to give 1-145. 

Scheme 1.44. Enantioselective synthesis of (-)-gilbertine (1-190) by a cationic domino cyclization.

Scheme 1.48. Cationic domino cyclization/hetero-Diels-Alder procedure.

Scheme 2.77. Iodine-induced domino cyclization affording the pyrrolidino-butyro-lactone...

Scheme 3.33. Lewis acid-promoted free radical domino cyclization reaction and enantioselective approach.

Scheme 3.80. Domino cyclization/1,5-hydrogen shift/hetero-Diels-Alder sequence.

Scheme 5.1. Stereoselective domino cyclization via photoinduced electron-transfer reaction.

Scheme 5.2. Proposed mechanism of the domino cyclization of photochemically induced reaction of 5-4.

The biomimetic cationic domino cyclization of an acyclic unsaturated substrate to give the tetracyclic scaffold of triterpenes and steroids is intensively described in the literature.1121 The concept has recently been used by Corey et al. to prepare enanti-opure (+)-dammarenediol II 18 in an exceptional short way.1131 The synthesis demonstrates the power of the combination of cation-olefin polyannulation with the aldol cyclization for tetraannulation (scheme 4). Successive treatment of the acylsilane 13 with 2-propenyllithium 14 and the iodoalkane 15 efficiently yidds the epoxytriene 16. The Lewis acid... 

Scheme 30. Rhodium-initiated domino cyclization for the synthesis of lycopodine 152...

Beyond the numerous applications of palladium in transition metal-catalyzed domino reactions there are a lot of other metals inducing domino processes. Ihara et al. found a strategy for the enan-tioselective synthesis of (+)-equilenin catalyzed by mangan and palladium complexes,1841 Whitby et al.1851 initiated domino cyclizations on a zirconocene template and furthermore Scherf et al. generated phenantrones by a nickel-mediated one-pot domino reaction.1861... 

Chiral information was introduced through the C3-building block 5 derived from lactic acid. The remaining two siereogenic centers in the natural product were provided under substrate control in the course of a domino cyclization... 

The formation of spirolactams 47-49 could be rationalized in terms of a sequence domino cyclization of a-allenols-cross coupling reactions. A palladium (Il)-catalyzed mechanism for the domino sequence leading to spiranic adducts 47-49 is proposed in Scheme 17. It could be presumed that the initially formed allenepalladium complex 50 undergoes an intramolecular attack by the hydroxyl group (oxypalladation), giving rise to the spirocyclic vinylic palladium species 51. 

The cyclic ylide intermediate 366, as a 1,3-dipole, is generated by intramolecular reaction of Rh-carbene with the ketone in 365, and undergoes cycloaddition with n-bonds to give the adduct 367 [121]. When a-diazocarbonyls have additional unsaturation, domino cyclizations occur to produce polycyclic compounds. The Rh-carbene method offers a powerful tool for the construction of complex polycyclic molecules in short steps, and has been applied to elegant syntheses of a number of complex natural products. 

The decomposition of 368 catalysed by Rh perfluorobutyrate and subsequent intramolecular cycloaddition give 370 in high yield (93%) as the key step in the total synthesis of lysergic acid (371), and is believed to involve the intramolecular reaction of the ylide intermediate 369 at the alkene. No C—H insertion takes place [122], Another elegant example is the efficient construction of the aspidosperma alkaloid skeleton 374. The Rh-catalysed domino cyclization cycloaddition of diazo irnide 372 afforded cycloadduct 374 in 95% yield as a single diastereomer via the dipole 373, and desacetoxy-4-oxo-6,7-dihydrovindorosine (375) has been synthesized from 374 [123]. 

Paulsen, H., Antons, S., Brandes, A., et al. (1999) Stereoselective Mukaiyama-Michael/Michael/Aldol domino cyclization as the key step in the synthesis of penta-substituted arenes an efficient access to highly active inhibitors of cholesteryl ester transfer protein (CETP). Angew. Chem. Int. Ed. 38, 3373-3375. 

The same palladium-catalyzed domino cyclization-anion capture sequence involving carbopalladation of allene (69), which was employed by Grigg et al. for the synthesis of diene 70 (Scheme 10) can yield 1,3,5-hexatriene 194, when starting from 2-bromo-l-ene-6-yne 193 instead of the aryl iodide 68 (Scheme 32) [52], Under the conditions of its formation, 194 immediately undergoes thermal 67r-electrocyclization to give the bicyclic product 195. 

Reaction conditions 1 eq lPy2BF4, 1 eq HBF4, CH2CI2, -80 °C. Scheme 1.32. Domino cyclization of a-.co-diynesuffides. 

Synthesis of 9-substituted tetrahydroazepinopurines as asmarine analogs has been described <03T6493>. In relation to adenosine receptor antagonists, new derivatives of pyrazolo[4,3-c][l,2,4]triazolo[l,5-c]pyrimidines have been synthesized <03IMC1229, 4287>. A one-pot synthesis of l,2,4-triazolo[l,5-c]quinazoline thiones 65, consisting of a domino cyclization of 2-isothiocyanatobenzonitrile 63 with hydrazides 64 has been published <03EJO182>. 

Hirota and coworkers [151-153] discovered an interesting rearrangement on the attempted Dieckmann cychzation of 354 (Scheme 119). Instead of 353, a tricyclic product 360 lacking the cyano group was obtained in 82% yield. The rearrangement was explained by the pyridyl ring migration and then domino cyclization, as indicated in the scheme. 

If the biosynthesis proceeds via a domino-cyclization, it would require a novel transformation, because the known reactions are not able to create such unfavored ring systems as that of 1. A possible substrate for a thermodynamically favorable reductive polycyclization with addition of 2 H atoms would be the allenic C2o-fatty acid 9,10,12,16,18,19-docosahexanoic acid (32). ... 

However, domino cyclization reactions had not been reported for diterpene synthesis. 

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