Cycloadditions cascade processes

Intramolecular cyclization-cycloaddition cascade reactions of rhodium carbenoids have been deployed to devise an approach towards the cytotoxic diterpenoids, pseudolaric acids [118,119]. Recently, pseudolaric acid A (120), possessing vast biological potential was successfully synthesized by Chiu and co-workers [120] (Scheme 37). The oxatricyclic intermediates 119a,b were derived from an intramolecular cyclization-cycloaddition cascade process of acycUc diazoketone 118 in the presence of a chiral rhodium(II) catalyst. A series of further functional group manipulations of the desired major isomer 119a has furnished pseudolaric acid A (120). 

Coldham and coworkers reported a tandem condensation/cyclization/intramolec-ular cycloaddition cascade process to form fused tricychc amines, using azomethine ylides (derived from a-amino-acids or esters). This chemistry was apphed for the constmction of the pyrrolo[l,2-a]azepine ring system of the Stemona alkaloids (Scheme 4.20) [39]. Condensation of the aldehyde 96 bearing a dipolarophile (an... 

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. 

Chromans possessing a fused isoxazolidine moiety 505 can be accessed via a palladium-catalyzed allene insertion-intramolecular 1,3-dipolar cycloaddition cascade reaction between ( )-fV-(2-hydroxybenzylidene)methanamine oxide, allene, and aryl iodides. This process creates two rings, two stereocentres and a quaternary carbon centre in one-pot (Equation 210) <2002CC1754>. 

Tandem carbonyl ylide generation from the reaction of metallo carbenoids with carbonyl continues to be of great interest both mechanistically and synthetically. Effective carbonyl ylide formation in transition metal catalyzed reactions of diazo compounds depends on the catalyst, the diazo species, the nature of the interacting carbonyl group and competition with other processes. The many structurally diverse and highly successful examples of tetrahydrofuran formation cited in this mini-review clearly indicate that the tandem cyclization/cycloaddition cascade of metallo carbenoids has evolved as an important strategy in both carbo- and heterocyclic synthesis. 

Alkynyl Fischer carbene complexes 64 (R = H) in the presence of a nitrone undergo a cascade cycloaddition/cyclopropanation process to afford 4-isoxazolines such as 65 in good yields. Under the same conditions, substituted complexes 64 (R = Me, Ph) gave naphthalenes 66 through a cycloaddition/metathesis process <07OL4143>. 

Rh(l)-catalyzed [2-I-2-I-2] cyclotrimerization of 1,6-diynes (e.g., 1391 and 1394) with monoynes (e.g., 1392) in combination with stereospecific Ag(i)-catalyzed aldimine (metallo)azomethine ylide — cycloaddition cascades affords rapid access to complex heterocyclic benzene derivatives 1393 and 1395 in one-pot processes with the generation of five new bonds, four stereocenters and three rings (Schemes 266 and 267) <2000T8967>. 

Iwasima and colleagues engineered the Pt-catalyzed [3h-2] cycloaddition of A-(<9-alkynylphenyl)imines with activated alkenes into a synthesis of the mitosene skeleton (Scheme 2, equation 1) [6]. The gold catalyst, AuBrj, is equally effective. Nakamura s group described a novel Pt-catalyzed dehydroalkoxylation/cyclization cascade process... 

The Diels-Alder reaction has a rich history of applications in tandem and cascade processes. Many of the transformations already discussed have a cascade-like nature since processes like retro-Diels-Alder reactions and aromatization reactions often occur after the initial Diels-Alder step. Clearly, the triple Diels-Alder reaction of [4]dendralene described by Sherbum (97—>98) involves a beautiful cascade of cycloaddition reactions. 

Nitrones have been widely exploited in various cycloaddition reactions. Intriguingly, these electrophilic species can also serve as the hydride acceptors. Sun and Xu et al. reported an expeditious access to structurally diverse oxadiazepines 108 via 1,5-hydride shift/cyclization of pyrrolidine- or tetrahydroiso-quinoline-containing nitrones 107 with nitrones as hydride acceptors and AICI3 was exploited as Lewis to promote the cascade process (Scheme 42) [121]. Furthermore, the nitrone 107 could be furnished in situ, which underwent subsequent 1,5-hydride shift, and ring cyclization through a one-pot process to afford 108 in good yields. 

Cycloaddition Cascades. These processes involve combinations of a starter molecule, which comprises a vinyl, aryl, al-lylic, or benzylic halide, triflate, etc., with one (or more) acceptor molecules (alkene, alkyne, 1,2-diene, 1,3-diene, etc.). Carbon monoxide is also a valuable one-carbon acceptor molecule. Other cycloaddition processes include Diels-Alder reactions, 1,3-dipolar cycloaddition reactions, etc., catalyzed by Pd (MeCN)2Cl2. 

CuOTf-catalyzed synthesis of polysubstituted pyrroles from a-diazoketones, nitroalkenes, and amines was reported by Lu, Wang, and coworkers. The corresponding polysubstituted pyrroles could be obtained in moderate yields using air as the oxidant. This cascade process of the polysubstituted pyrrole formation involves an NH insertion of carbene, a copper-catalyzed oxidative dehydrogenation of amine, and a [3+2] cycloaddition of azomethine ylide [21] (Scheme 8.9). 

The Rh-catalyzed intramolecular cycloaddition has proven reliable for the construction of polycyclic carbocycles and heterocycles. The cascade processes involving this reaction have also been achieved. A recent example is the cascade intramolecular hetero-[5 + 2] cycloaddition/Claisen rearrangement reaction of vinylic oxirane-aUcyne substrates 73, which uses the rhodium NHC complex as catalyst and provides atom-economical, regiospecific, and diastereoselective access to [3.1.0] bicyclic products 74 (Scheme 5.50) [48]. 

Compared to the cycloadditions of nitroalkenes, tandem cycloadditions of 1,3,4-oxadiazoles consist not of two, but of three elementary reactions. In the first step, a 1,3,4-oxadiazole 428 serves as an electron-poor heterodiene (4jt-component) and reacts thermally with an alkene dienophile (2jt-componait) by a [4-1-2] cycloaddition reaction. The preferred dienophile is electron-rich, unhindered, and strained. At the elevated temperatures required for the first step [169], the immediate product of this reaction, 430, is unstable and undergoes extrusion of dinitrogen by a [3 + 2] cycloreversion to form dipole 431 [170]. At the high temperatures required for its formation, 431 cannot be directly observed either and reacts by a [3 + 2] cycloaddition with an available dipolarophUe, which can be the same 27i-component that served as the dienophile or something else. Because none of the intermediates is isolated and no change in reaction conditions is required, tandem [4-f 2]/[3- -2] cycloadditions of 1,3,4-oxadiazoles are tandem cascade processes as defined earlier in this chapter. 

A domino Diels-Alder reaction (the term was chosen from the well-known game) is a one-pot process involving two or more Diels-Alder reactions carried out under the same reaction conditions without adding additional reagents or catalyst such that the second, third, etc., cycloaddition is the consequence of the functionality generated in the previous reaction. A historical example is illustrated in Equation 1.28 [60]. This type of transformation is sometimes named tandem or cascade, but these terms seem less appropriate for describing a time-resolved transformation. 

Recently, Denmark and coworkers have developed a new strategy for the construction of complex molecules using tandem [4+2]/[3+2]cycloaddition of nitroalkenes.149 In the review by Denmark, the definition of tandem reaction is described and tandem cascade cycloadditions, tandem consecutive cycloadditions, and tandem sequential cycloadditions are also defined. The use of nitroalkenes as heterodienes leads to the development of a general, high-yielding, and stereoselective method for the synthesis of cyclic nitronates (see Section 5.2). These dipoles undergo 1,3-dipolar cycloadditions. However, synthetic applications of this process are rare in contrast to the functionally equivalent cycloadditions of nitrile oxides. This is due to the lack of general methods for the preparation of nitronates and their instability. Thus, as illustrated in Scheme 8.29, the potential for a tandem process is formulated in the combination of [4+2] cycloaddition of a donor dienophile with [3+2]cycload-... 

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... 

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