Transition metal catalysts carbenoids

In recent years, much attention has been focused on rhodium-mediated carbenoid reactions. One goal has been to understand how the rhodium ligands control reactivity and selectivity, especially in cases in which both addition and insertion reactions are possible. These catalysts contain Rh—Rh bonds but function by mechanisms similar to other transition metal catalysts. 

Another remarkable property of iodorhodium(III) porphyrins is their ability to decompose excess diazo compound, thereby initiating carbene transfer reactions 398). This observation led to the use of iodorhodium(III) me.vo-tetraarylporphyrins as cyclopropanation catalysts with enhanced syn anti selectivity (see Sect. 2.2.3) s7, i°o) as wep as catalysts for carbenoid insertion into aliphatic C—H bonds, whereby an unusually high affinity for primary C—H bonds was achieved (see Sect. 6.1)287). These selectivities, unapproached by any other transition metal catalyst,... 

Suga et al. (197) reported the first stereocontrolled 1,3-dipolar cycloaddition reactions of carbonyl ylides with electron-deficient alkenes using a Lewis acid catalyst. Carbonyl ylides are highly reactive 1,3-dipoles and cannot be isolated. They are mainly generated through transition metal carbenoid intermediates derived in situ from diazo precursors by treatment with a transition metal catalyst. When methyl o-(diazoacetyl)benzoate is treated with A-methylmaleimide at reflux... 

Transition metal catalysts that are effective for carbenoid transformations include those of copper , palladium(II) or platinum(II), eobalt(II), and rhodium(II) (7-3, 6-3), but only copper and rhodium catalysts have been routinely employed. 

Diazocarboxylate esters can be transformed by transition metal catalysts such as rhodium(II) acetate into alkoxycarbonylcarbenes that undergo a wide variety of synthetically useful C-H, C-C, C-X, X-H and X-X insertion reactions (where X = heteroatom) [99]. Chemoselectivity of rhodium carbenoids derived from Rh(II) carboxylates and carboxamides has been found to exhibit striking ligand dependency, for example in work by Padwa showing that perfluorocar-boxamide ligands exclusively promoted aromatic C-H insertions in Rh(II)-cat-alyzed decomposition of diazoamides to give oxindoles, whereas a carboxylate-based rhodium catalyst promoted other types of insertions and addition reactions [100]. 

Development of chiral transition-metal catalysts enables one to perform the catalytic C—H insertion to metal carbenoids, generated from diazo compounds, in an enantioselective manner. Davies et al. reported that the asymmetric intramolecular reaction of the aryldiazoacetates 684 in the presence of Rh2-(S-DOSP)4 gave the C-H insertion products 685 (Scheme 212). 288b The enantioselectivity is strongly dependent on the site of the C-H activation the highest enantioselectivity was obtained for insertion into the methyne C—H bond. 

Compund 78 is among the new transition metal catalysts that have found good use in the decomposition of diazo compounds and delivery of the metal carbenoids to alkenes." Iminodiazaphospholidine (79) possesses a stereogenic phosphorus center and its applicability to effect asymmetric cyclopropanation" is now known. The Zn chelate of 80 is effective for the Simmons-Smith reaction of allylic alcohols. ... 

The understanding of this catalysis started in 1952, shortly after the concept of carbenes was introduced (see Sect. 8.1). Yates postulated that transition-metal catalysts react with diazo compounds by formation of transient electrophilic metal carbenes, because that complex can be depicted as a metal-stabilized carbocation (8.104). Doyle (1986 a) proposed the catalytic cycle (8-46) for the formation of the carbenoid 8.104 and its reaction with an electron-rich substrate S . The reagent S is, first of all, an alkene in cyclopropanation, but can also belong to other groups of compounds, to be discussed later in this section. 

It was mentioned earlier that the S,C-ylide (139b) generates a carbenoid species and dichloro-thiophene in the presence of transition metal catalysts. Thermolysis of (139b) in the absence of such metal catalysts leads to (145) through an intramolecular rearrangement <84CHEC-i(4)74i, 89AHC(45)151>. 

The decomposition of suitably crafted diazoimides 181, in the presence of a transition metal catalyst, affords the metallo-carbenoids 182 that undergo intramolecular cycUzation onto the neighboring amide carbonyl oxygen to form the five-membered ring carbonyl yUdes (isomiinchnones) 183 (Scheme 58). Early examples of inter- and intramolecular 1,3-dipolar cycloaddition of the mesoionic ylides 183 have mainly emanated from the research groups of Ibata [149], Maier [150] and Padwa [151]. These reactive species (isomimchnones) can be trapped by various electron-rich and electron-deficient dipolarophiles [152] to furnish the cycloadducts in high yield. Much work has been reported in this area and for clarity of presentation is described here under various subheadings. 

Arenes suffer dearomatization via cyclopropanation upon reaction with a-diazocarbonyl compounds (Btlchner reaction) [76]. Initially formed norcaradiene products are usually present in equilibrium with cycloheptatrienes formed via electrocyclic cyclopropane ring opening. The reaction is dramatically promoted by transition metal catalysts (usually Cu(I) or Rh(II) complexes) that give metal-stabilized carbenoids upon reaction with diazo compounds. Inter- and intramolecular manifolds are known, and asymmetric variants employing substrate control and chiral transition metal catalysts have been developed [77]. Effective chiral catalysts for intramolecular Buchner reactions include Rh Cmandelate), rhodium carboxamidates, and Cu(I)-bis(oxazolines). While enantioselectivities as high as 95% have been reported, more modest levels of asymmetric induction are typically observed. 

Many rhodium(II) complexes are excellent catalysts for metal-carbenoid-mediated enantioselective C-H insertion reactions [101]. In 2002, computational studies by Nakamura and co-workers suggested the dirhodium tetracarboxylate catalyzed diazo compounds insertion reaction to alkanes C-H bonds proceed through a three-centered hydride-transfer-like transition state (Fig. 25) [102]. Only one rhodium atom of the catalyst is involved in the formation of rhodium carbene intermediate, while the other rhodium atom served as a mobile ligand, which enhanced the electrophilicity of the first one and facilitate the cleavage of rhodium-carbon bond. In this case, the metal-metal bond constitutes a special example of Lewis acid activation of Lewis acidic transition-metal catalyst. 

It is not known whether or not this transformation is catalyzed by the transition metal. However, the metal-catalyzed ring-opening reaction of (3-alkoxycyclopropane carboxylates yielding vinyl ethers (e.g. 50 -> 51 and 52 - 53) is well documented 97 120 . Several catalysts are suited [PtCl2 2 PhCN, Rh2(OAc)4, [Rh(CO)2Cl]2, [Ru(CO)3Cl2]2, Cu bronze, CuCl], but with all of them, reaction temperatures higher than those needed for the carbenoid cyclopropanation reaction are required. 

Using the results of an earlier study concerning enantioselective copper-catalyzed intramolecular C—H insertion of metal carbenoids,109 an interesting system for optimizing the proper combination of ligand, transition metal, and solvent for the reaction of the diazo compound (75) was devised (see Scheme 19).110 The reaction parameters were varied systematically on a standard 96-well microtiter/filtration plate. A total of five different ligands, seven metal precursors, and four solvents were tested in an iterative optimization mode. Standard HPLC was used to monitor stereoselectivity following DDQ-induced oxidation. This type of catalyst search led to the... 

A select number of transition metal compounds are effective as catalysts for carbenoid reactions of diazo compounds (1-3). Their catalytic activity depends on coordination unsaturation at their metal center which allows them to react as electrophiles with diazo compounds. Electrophilic addition to diazo compounds, which is the rate limiting step, causes the loss of dinitrogen and production of a metal stabilized carbene. Transfer of the electrophilic carbene to an electron rich substrate (S ) in a subsequent fast step completes the catalytic cycle (Scheme I). Lewis bases (B ) such as nitriles compete with the diazo compound for the coordinatively unsaturated metal center and are effective inhibitors of catalytic activity. Although carbene complexes with catalytically active transition metal compounds have not been observed as yet, sufficient indirect evidence from reactivity and selectivity correlations with stable metal carbenes (4,5) exist to justify their involvement in catalytic transformations. 

Abstract This review gives an insight into the growing field of transition metal-catalyzed cascades. More particularly, we have focused on the construction of complex molecules from acyclic precursors. Several approaches have been devised. We have not covered palladium-mediated cyclizations, multiple Heck reactions, or ruthenium-catalyzed metathesis reactions because they are discussed in others chapters of this book. This manuscript is composed of two main parts. In the first part, we emphasize cascade sequences involving cycloaddition, cycloisomerization, or ene-type reactions. Most of these reaction sequences involve a transition metal-catalyzed step that is either followed by another reaction promoted by the same catalyst or by a purely thermal reaction. A simple change in the temperature of the reaction mixture is often the only technical requirement to go from one step to another. The second part covers the cascades relying on transition metalo carbenoid intermediates, which have recently undergone tremendous... 

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. 

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