Silver-Catalyzed Cycloisomerization Reactions

Laboratory for Organometallic Chemistry, Heterocycles and Biological Targets, 

Unit 176 Conception, Synthesis and Targeting of Biomolecules, Institut Curie and CNRS, Paris, France 

Although silver chemistry has a long history in organic chemistry, it has typically been used in stoichiometric amounts and is developed mostly for anion metathesis 

Silver in Organic Chemistry Edited by Michael Harmata Copyright 2010 John Wiley Sons, Inc. 

The chemical reactions possible with silver catalysis are multiple and cover cycloadditions, cycloisomerizations, allylations, aldol reactions, and even C-H bond activation. Also, asymmetric versions are known, even though they still need to be improved.3-10 

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Our interest in this chapter is in silver-catalyzed cycloisomerization reactions. Therefore, we shall present different silver-catalyzed cycloisomerization reactions as a function of the nucleophilic and electrophilic moiety. Cycloisomerization reactions including the classical ene-yne cycloisomerization (with X = CHR, Scheme 5.1), and the related heterocyclization reactions with heteroatoms embedded in unsaturated systems (X = NR, O Scheme 5.1) belong to the same reaction family. In addition, the alkynyl part can be exchanged for an allene unit. Internal or external nucleophiles (Nu) can then stabilize, through cascade reactions, the positive charge created.24... 

This overview of silver-catalyzed cycloisomerization reactions shows the great flexibility of the method and its usefulness in reaching the core of numerous heterocycles. 

The latter mode of reaction has even been reported to proceed in presence of sil-ver(I) ions [127], which is not easy to understand in the context of Marshall s silver-catalyzed cycloisomerization of allenyl ketones (see Chapter 15). 

Allenic Alder-ene reactions, characteristics, 10, 584 Allenic carbonyl compounds reductive cyclization, 10, 524 silver-catalyzed cycloisomerizations, 9, 559 Allenic carboxylic acids, silver-catalyzed cycloisomerizations, 9, 559... 

Heterocyclization reactions with saturated moieties (alcohols, amines, thiols, etc.) or acids on unsaturated counterparts (alkenes, allenes, alkynes, etc.) are not covered in this chapter since they are addition, and not isomerization, reactions. Silver is also widely used as an activating agent for producing highly reactive metallic cations (anion metathesis), which, in turn, may catalyze cycloisomerization reactions. This aspect is covered only when the silver control experiments give substantial positive results. 

Silver-catalyzed cyclization reactions of allenic carbonyl compounds were applied for the total synthesis of various natural products, including rubifolide,331 kallolide A and B,332,332a and deoxypukalide.333 In their total synthesis of the enantiomer of rubifolide 396, Marshall and Sehon331 took advantage of the silver-catalyzed cycloisomerization of the allenic ketone 393 to the furan 394, as well as of the analogous reaction of the allenic carboxylate 395 to the target molecule 396 (Scheme 115). 

Marshall and co-workers used the silver-catalyzed version of this cycloisomerization as the final step in the synthesis of (-)-kallolide B from precursor 115 (Scheme 15.33) [51, 54]. Again, the reaction is stereospecific, as has also been demonstrated in the synthesis of kallolide A [55] and other examples [77]. 

Silver salts or reagents have received much attention in preparative organic chemistry because they are useful catalysts for various transformations involving C-G and C-heteroatom bond formation.309 Especially, the silver(i)/ BINAP (2,2 -bis(diphenylphosphino)-l,T-binaphthalene) system is a very effective catalyst for a variety of enantio-selective reactions, including aldol, nitroso aldol, allylation, Mannich, and ene reactions. Moreover, silver salts are known to efficiently catalyze cycloisomerization and cycloaddition reactions of various unsaturated substrates. Recently, new directions in silver catalysis were opened by the development of unique silver complexes that catalyze aza-Diels-Alder reactions, as well as carbene insertions into C-H bonds. 

Two different research groups independently reported metal-catalyzed cycloisomerizations of alkynyl-substituted pyridines leading to indolizines. Specifically, treatment of pyridine 7 with silver tetrafluoroborate gave indolizine 8 in excellent yield <07OL3433>. This reaction could also be mediated by copper(I) iodide <07JOC7783>. 

An efficient and one-pot synthesis of multisubstituted pyrroles with high diversity and in a regioselective manner from the reactions of suitably substituted (Z)-enynols with amines or sulfonamides under mild reaction conditions has been developed (Lu et al. 2009). This synthesis was realized via a cascade process in the presence of gold/ silver (Au/Ag) or boron trifluoride etherate/gold/silver (BFj EtjO/Au/Ag) catalysts, which could catalyze amination and cycloisomerization reactions in the same vessel. Scheme 11.2 illustrates that either silver trifluoromethanesuUbnale or a mixture of... 

The cycloisomerization of allenyl ketones was initially described as being catalyzed by rhodium(I) or silver(I) by Marshall et al.21 The activity of copper, silver, and gold for this reaction was first compared in two papers published later (Scheme 12.7).22 In the case of copper and silver, only a cycloisomerization was observed (Table 12.4, entries 1 and 2) with gold, a dimer is obtained as well (entry 3). 

Further silver(l)-catalyzed syntheses of pyrroles include the cycloisomerization of W-allyl-W-propargylamines to afford 3-vinylidenepyrrolidines, which can be isomerized to 3-vinyl-3-pyrrolines [44]. The reaction of /1-alkynylketones with primary amines in the presence of silver(l) or gold(l) catalysts provides functionalized pyrroles in good yields [45]. 

The cycloisomerization of a-allenyl ketones to the corresponding substituted furans was the first example of a gold-catalyzed addition of an oxygen nucleophile to an allene (Scheme 4-86). Traditionally, silver or palladium catalysts were employed for cyclizations of this type advantages of gold catalysis incluiie shorter reaction times, milder conditions, an or lower catalyst loadings. Variable amounts of... 

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