Cyclization cascade

As an alternative to polyepoxide cyclization, cascade cyclization of cyclic sulfates... 

Employing their catalytic system, the group of Oltra and Cuerva demonstrated that 7-endo cyclizations can be performed in surprisingly high yields. Moreover, 7-endo-cyclizations were used by the same group in elegant catalytic cyclization cascades for the preparation of a number of natural products as shown in Scheme 33 [125]. Barreo et al. reported similar methodology [105]. 

In turn, the propensity of 1 to respond to steric hindrance can be used to control the site of initiation of an RCM reaction in a polyene substrate (Scheme 9) [20]. Thus, dienyne 25 reacts with the catalyst regioselectively at the least substituted site the evolving ruthenium carbene 26 undergoes a subsequent enyne metathesis leading to a new carbene 27, which is finally trapped by the disubsti-tuted olefin to afford the bicyclo[4.4.0]decadiene product 28. By simply reversing the substitution pattern of the double bonds, the complementary bicyclo [5.3.0] compound 32 is formed exclusively, because the cyclization cascade is then triggered at the other end of the substrate. Note that in both examples tri-substituted olefins are obtained by means of a ruthenium based metathesis catalyst [20] ... 

An uncatalyzed amination/aza-Claisen rearrangement/cyclization cascade described by Majumdar et al. was terminated by a final six-membered ring for-... 

Additionally, dimedone derivative 241 and propargylamine 234 could be combined to give the alkynyl vinyl amine 242. The rearrangement/cyclization cascade could be induced upon heating until reflux in chlorobenzene. The an-... 

Balme G, Bouyssi D, Monteiro N (2006) The Virtue of Michael-Type Addition Processes in the Design of Transition Metal-Promoted Cyclizative Cascade Reactions. 19 115-148 Barluenga J, Rodriguez F, Fanands FJ, Fldrez J (2004) Cycloaddition Reaction of Group 6 Fischer Carbene Complexes. 23 59-121 Basset J-M, see Candy J-P (2005) 16 151-210... 

The domino cycloaddition-iV-acyliminium ion cyclization cascade has been extensively reviewed. Tandem reactions combining Diels-Alder reactions and sigma-tropic rearrangement reactions in organic synthesis have been extensively reviewed. The tandem Diels-Alder reaction between acetylenedicarboxaldehyde and N,N -dipyrrolylmethane has been extensively studied at the RHT/3-21G and RHF/6-31G levels.The molecular mechanism of the domino Diels-Alder reaction between hexafluorobut-2-yne and A,A -dipyrrolylmethane has been studied using density functional theory. 

In 2007, Terada et al. extended their previously described chiral phosphoric acid-catalyzed aza-ene-type reaction of M-acyl aldimines with disubstituted enecarbamates (Scheme 28) to a tandem aza-ene-type reaction/cyclization cascade as a one-pot entry to enantioenriched piperidines 121 (Scheme 48). The sequential process was rendered possible by using monosubstituted 122 instead of a disubstituted enecarbamate 76 to produce a reactive aldimine intermediate 123, which is prone to undergo a further aza-ene-type reaction with a second enecarbamate equivalent. Subsequent intramolecular cychzation of intermediate 124 terminates the sequence. The optimal chiral BINOL phosphate (R)-3h (2-5 mol%, R = 4-Ph-C H ) provided the 2,4,6-sub-stituted M-Boc-protected piperidines 121 in good to exceUent yields (68 to > 99%) and accomplished the formation of three stereogenic centers with high diastereo- and exceUent enantiocontrol (7.3 1 to 19 1 transicis, 97 to > 99% ee(trans)) [72]. 

Scheme 48 Tandem aza-ene-type reaction/cyclization cascade scope and reaction intermediates...

On addition of S04 to the triple bond in the lO-member cycloalkyne 24 and cyclo-aUcynone 27, a nonchain, and anionic, self-terminating radical cyclization cascade is induced. In the former reaction (equation 22) the bicyclic ketones 25 and 26 are formed, and in the latter reaction (equation 23) the a,/3-epoxy ketones 28 and 29 are formed in good yields. Because of the difficulty of oxidizing isolated triple bonds, 804 does not react as an electron-transfer reagent in these reactions but acts as a donor of atomic oxygen. 

Padwa et al. (187,188) concisely summarized his domino cycloaddition/ A -acyliminium ion cyclization cascade process, which involves sequentially the generation of an isomiinchnone 1,3-dipole, intramolecular 1,3-dipolar cycloaddition reaction, 77-acyliminium ion formation, and, hnally, Mannich cyclization. Kappe and co-workers (189) utilized Padwa s cyclization-cycloaddition cascade methodology to construct several rigid compounds that mimic the putative receptor-bound conformation of dihydropyridine-type calcium channel modulators. 

Keywords ninhydrin, dimedone, aminocrotonate,, cyclization, cascade reaction, waste-free, solid-solid reaction... 

Keywords acetone, o-phcnylcndiaminc, cyclization, cascade reaction, gas-solid reaction, benzodiazepine, benzothiazolidine... 

Keywords o-phenylendiamine, parabanic acid, cyclization, cascade reaction, melt reaction, quinoxaline... 

This rearrangement-cyclization cascade was applied to natural products synthesis. For example, DDQ oxidation of the appropriate dihydro-3 (27T)-furanone enol acetates (Table 3.5, entries 1 and 7) afforded bullatenone and the antitumor agent geiparvarin in a very rapid route (Fig. 3.1).69 70... 

Figure 3.1. Synthetic applications of the rearrangement-cyclization cascade toward natural products.

The formation of /3-hydroxyselenides through the reaction of a selenium-stabilized carbanion with carbonyl compounds has been extensively used also in the context of natural product synthesis. The phenylselenoalkyllithium compound 115 was reacted with aldehyde 116 to afford /3-hydroxyselenide 117. In a radical cyclization cascade the tricyclic molecule 118 was generated in good yields and subsequent transformations led to the synthesis of pentalenene 119 (Scheme 28).1 9 Also other natural products like zizaene and khusimone have been synthesized via a similar route.200... 

RYNKIEWICZ, M. J., CANE, D. E CHRISTIANSON, D. W., Structure of trichodiene synthase from Fusarium sporotrichioides provides mechanistic inferences on the terpene cyclization cascade, Proc. Natl. Acad. Sci. USA, 2001, 98, 13543-13548. 

The Virtue of Michael-Type Addition Processes in the Design of Transition Metal-Promoted Cyclizative Cascade Reactions... 

Intermolecular Addition-Indole Cyclization Cascade Reactions... 

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