Functionalization metal-catalyzed cycloadditions

The reaction of isocyanide 42 and phenylacetylene (43) afforded pyrrole 44 under silver-catalyzed conditions. The pyrroles are formed regioselec-tively, in high yields, and with broad functional group tolerance. This represents the first example of the transition metal-catalyzed cycloaddition of isocyanides with unactivated terminal alkynes (13AG(I)6953). A similar system for the synthesis of substituted pyrroles was reported by Lei (13AG(1)6958). 

Transition metal-catalyzed carbenoid transfer reactions, such as alkene cyclopro-panation, C-H insertion, X-H insertion (X = heteroatom), ylide formation, and cycloaddition, are powerful methods for the construction of C-C and C-heteroatom bonds [1-6]. In contrast to a free carbene, metallocarbene-mediated reactions often proceed stereo- and regioselectively under mild conditions with tolerance to a wide range of functionalities. The reactivity and selectivity of metallocarbenes can be... 

During the present decade, a wide variety of polycyclic carbacephem derivatives have been reported starting from readily available monocyclic /3-lactams, which after transformation in more functionalized compounds and further cyclization yielded different fused carbacephems. Several approaches for the preparation of fused carbacephem derivatives including cycloaddition reactions such as the [2+2], 1,3-dipolar, and Diels-Alder reactions, as well as transition metal-catalyzed reactions such as the Pauson-Khand and ring-closing metathesis (RCM) reactions have been reported in the literature. 

Metal complexes enable one to employ molecules that are thermally unreactive toward cycloadditions by taking advantage of their ability to be activated through complexation. Most of the molecules activated by transition-metal complexes involve C-C unsaturated bonds such as alkynes, alkenes, 1,3-dienes, allenes, and cyclopropanes. In contrast, carbonyl functionalities such as aldehydes, ketones, esters, and imines seldom participate in transition-metal-catalyzed carbonylative cycloaddition reactions. Recently, such a transformation was reported via the use of ruthenium complexes. 

While most of the initial studies have involved the transition metal-catalyzed decomposition of a-carbonyl diazo compounds and have been reviewed [3-51], it appears appropriate to highlight again some milestones of these transformations, since polycyclic structures could be nicely assembled from acyclic precursors in a single step. Two main reactivities of metalo carbenoids derived from a-carbonyl diazo precursors, namely addition to a C - C insaturation (olefin or alkyne) and formation of a ylid (carbonyl or onium), have been the source of fruitful cascades. Both of these are illustrated in Scheme 27 [52]. The two diazo ketone functions present in the same substrate 57 and under the action of the same catalyst react in two distinct ways. The initially formed carbenoid adds to a pending olefin to form a bi-cyclop. 1.0] intermediate 58 that subsequently cyclizes to produce a carbonyl ylide 59, that is further trapped intramolecularly in a [3 + 2] cycloaddition. The overall process gives birth to a highly complex pentacyclic structure 60. 

As with other diazo compounds, cyclopropanation with 1 or 2 can proceed either via a photo-chemically or thermally generated carbene, in a transition-metal-catalyzed reaction, or by [3 -I- 2] cycloaddition of the diazo function to the C-C double bond followed by nitrogen extrusion from the thermally unstable cycloadduct. 

A further possibility exists for employing substituted cyclopropane substrates in metal-catalyzed [3 + 2] cycloadditions to electron-deficient olefins. Once again, it involves the use of palladium(O) complexes in the presence of a phosphane ligand [bis(diphenylphospino)ethane (dppe) or tributylphosphane], A vinylcyclopropane geminally ring-substituted by ester functionalities enables realization of such a process52. 

Trost et al. discovered that COD can formally function as a bis-homodiene in metal-catalyzed [4+2]cycloadditions. A 0.1 M solution of the alkyne 1 reacts with 1.1 equivalents of COD in the presence of 5 mol% of chlo-Toiti -cyclooctadieneX -cyclopentadienyl)-ruthenium(II) [CpRu(COD)Cl] [3] (2) in boiling methanol to give derivatives 3 of tricy-clo[4.2.2.0 ]dec-7-ene (Scheme 1). Yields of between 78 and 100% are achieved in seven out of eight examples. Electron-defi-... 

Intramolecular [3+2] cycloaddition reactions of unsaturated diazocarbonyl compounds as well as transition-metal-catalyzed intramolecular carbene-type reactions of diazo compounds constitute an important strategy in contemporary synthesis of alicyclic and heterocyclic systems [1]. In a program directed towards the synthesis of silaheterocycles according to this concept, we have used various silicon-functionalized (silyl)diazoacetates [2] as starting materials. In this communication, we report on the synthesis of silaheterocycles from a-(alkynyloxy)silyl-a-diazoacetates [3], which can be prepared easily by successive reaction of a silyl bis(triflate) with an alkyl diazoacetate and a propargyl alcohol [4],... 

The preparation of cyclopentenone from the three-component transition-metal-catalyzed [2+2+1] cycloaddition of an alkyne, alkene, and carbon monoxide in the presence of a stoichiometric amount of Co2(CO)g was first reported by Khand et al. in 1973 (Scheme 2-l2)P This reaction is attractive for organic synthesis as it tolerates a wide variety of functionalities including esters, ethers, tertiary amines, amides, and alcohols. 

In 2010, a methodology for the synthesis of 1,2,3-triazole-fused iso-indolines and dihydroisoquinolines was reported. Starting from easily available terminal allgmes and (2-haloaryl)allq7lazides, the desired products were formed in good to exeellent yields. This method is based on a cycloaddition reaction, via Click chemistry, followed by a transition-metal-catalyzed functionalization of a C-H bond. Later on, a one-pot procedure was reported as well. °... 

Transition metal-catalyzed cyclopropane-based cycloadditions provide efficient strategies for the construction of (poly)cyclic structures. More importantly, the cycloadditions feature atom- and step-economy, good regio- and stereoselectivity, and excellent functional group tolerance. More and more total syntheses of natural products benefit fi om the rich cycloaddition chemistry of VCPs and MCPs. To date, numerous total syntheses of natural products have been accomplished utilizing these methodologies as key steps. Listed in Fig. 4 are some selected examples. 

In the field of metal-catalyzed asymmetric cycloadditions, [2+2] cycloaddition seems to be relatively rare due to the ring strain force of the products. In 2010, Studer and co-workers presented the first Cu(I)/Walphos-catalyzed enantioselective [2+2] cycloaddition of 2-nitrosopyridine with various ketenes to afford synthetically valuable 1,2-oxazetidine-3-ones with good enantioselectivity (Scheme 33) [58]. Density function theory (DPT) calculations give evidence that the reaction occurs via a concerted pathway. 

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