Cyclization 2+2+1 cycloaddition

CATEGORY llegf CYCLIZATIONS - CYCLOADDITIONS INVOLVING PYRROLE-2,3-QUINODIMETHANE INTERMEDIATES AND EQUIVALENTS... 

Tandem cyclization-cycloaddition of diazoketones in the synthesis of some alkaloids 97F303. 

Uemura M (2004) (Arene)Cr(Co)3 Complexes Cyclization,Cycloaddition and Cross Coupling Reactions. 7 129-156 Ujaque G, see Drudis-Sole G (2005) 12 79-107... 

Graening, T, Friedrichsen, W., Lex, J., Schmalz, H.G. (2002) FacUe Construction of the Colchicine Skeleton by a Rhodium-Catalyzed Cyclization/Cycloaddition Cascade. Angewandte Chemie International Edition, 41, 1524-1526. 

In an alternative approach to annulation across the indole 2,3-tt system, Padwa and coworkers have reported approaches to the pentacyclic and hexacyclic frameworks of the aspidosperma and kopsifoline alkaloids respectively that involve as the key step a Rh(II)-promoted cyclization-cycloaddition cascade <06OL3275, 06OL5141>. As illustrated in their approach to ( )-aspidophytine 150, Rh2(OAc)4-catalyzed cyclization of a diazo ketoester 148 affords a carbonyl ylide dipole that undergoes [3+2]-cycloaddition across the indole 2,3-tt bond to generate 149 <06OL3275>. 

Padwa and co-workers (36-38) developed a process concerning a tandem carbene cyclization-cycloaddition sequence that led to the formation of products of greater complexity in a single step (Scheme 4.25). 

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. 

Pummerer reaction conditions was followed by cycUzation to isomilnchnone 292 and hence to cycloadduct 293, which loses water to form a-pyridone 294. Subsequent manipulation involving deoxygenation and debenzylation completed the synthesis. In similar fashion, the azaanthraquinone alkaloid dielsiquinone was synthesized for the first time. Also, the quinolizidine alkaloids ( )-lupinine and ( )-anagyrine, and the ergot alkaloid ( )-costaclavine were synthesized using this Pummerer cyclization-cycloaddition cascade of imidosulfoxides and isomiinch-nones. 

Cyclization-cycloaddition of an a-diazoacetophenone. Reaction of 1 with Rh2(OAc)4 in C6H6 at 25° results in 2 in 87% yield. This reaction is considered to involve a carbonyl ylide (a), which is trapped internally by the neighboring double bond.2... 

In summary, the metal-catalyzed decomposition of diazo compounds results in a broad array of opportunities for the development of new asymmetric catalytic transformations. In the last few years considerable advances have been made in enantioselective intermolecular C-H insertion, novel cycloadditions, and tandem cyclization/cycloadditions. These new transformations offer new strategies for the rapid enantioselective construction of complex structures. 

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]. 

Cyclization cycloaddition route to oxapolycycles (13, 266). The reaction of l-diazo-2,5-hexanedione (l)1 (or of l-diazo-5-phenyl-2,5-pentanedione2) with Rh2(OAc)4 provides an adduct a that reacts with an aldehyde to form the ring system 2, which can be used as a precursor to brevicomin (3). 

Cycloadduct 212 was subsequently converted to desacetoxy-4-oxo-6,7-dihy-drovindorosine 211 via intermediate 217 in high overall yield thereby proving the merits of the method. The tandem cyclization-cycloaddition sequence is particularly attractive as four of the stereocenters are formed in one step with a high degree of stereocontrol. 

In the same vein, Schmalz has proposed a facile construction of the colchicine skeleton by a rhodium-catalyzed cyclization/cycloaddition cascade [56]. A TMS group has to be introduced on the alkyne moiety of 66 in order to avoid participation of the relatively acidic alkynyl hydrogen atom in undesired proton transfers. The resulting 6,7,7 of 67a and 67b architecture was assembled in a remarkably diastereoselective manner (14 1) and in satisfactory yield (Scheme 30). 

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