Carbenes, generation metal

Carbenes and transition metal carbene complexes are among the few reagents available for the direct derivatization of simple, unactivated alkanes. Free carbenes, generated, e.g., by photolysis of diazoalkanes, are poorly selective in inter- or intramolecular C-H insertion reactions. Unlike free carbenes, acceptor-substituted carbene complexes often undergo highly regio- and stereoselective intramolecular C-H insertions into aliphatic and aromatic C-H bonds [995,1072-1074,1076,1085,1086],... 

ASYMMETRIC ADDITION AND INSERTION REACTIONS OF CATALYTICALLY-GENERATED METAL CARBENES... 

The development of chiral transition-metal catalysts for these transformations has taken place during the evolution of mechanistic understanding for metal carbene generation. Concepts applied to the design of chiral catalysts have been influenced by these mechanistic developments, and further refinements can be expected. 

Although exceptional diastereocontrol and enantiocontrol can now be achieved in C-H insertion reactions of catalytically generated metal carbenes, further improvements are needed. Insertion into tertiary C-H bonds occurs with diminished enantiocontrol and regiocontrol [131,132], In addition, chiral dirhodium carboxamidates do not react with a-diazo-p-ketocar-bonyl compounds. Thus, the potential for their impact on a broad range of C-H insertion processes is yet to be tested. 

Carbenes, generated by several methods, are reactive intermediates and used for further reactions without isolation. Carbenes can also be stabilized by coordination to some transition metals and can be isolated as carbene complexes which have formal metal-to-carbon double bonds. They are classified, based on the reactivity of the carbene, as electrophilic heteroatom-stabilized carbenes (Fischer type), and nucleophilic methylene or alkylidene carbenes (Schrock type). 

Nickel-catalyzed cyclization of a 1,3-diene side chain of the substituted pyrrolidones yields a precursor to the indolizidine alkaloid (—)-elaeokanine C (Equation 86) <1997TL3931>. Other metal-catalyzed reactions include the Rh-induced in situ carbene generation and subsequent cyclization onto the heteroatom to yield piperidines <1997T16565, 1997JOC67>. Pauson-Khand cyclizations have also been used (Equation 87) <1997T6611>. 

M. P. Doyle, Asymmetric Addition and Insertion Reactions of Catalytically-Generated Metal Carbenes, in Catalytic Asymmetric Synthesis, Ed. I. Ojima, Wiley-VCH, New York, 2nd ed., 2000, 191-228. 

Molecular models are available for all the reactions and intermediates invoked in these mechanisms. For example, diazoalkanes have been known to generate metal-carbene complexes, with the cyclopropanation of metal-metal double bonds under smooth conditions (compare Section 3.1.7) being of particular relevance to the chemistry of metal surfaces, cf. eq. (10) [8 a, 23],... 

Whereas free singlet carbenes are rather unselective with respect to formation of cyclopropane 22 or ylide 23 and the cyclopropane is favored under conditions that populate the triplet state of a carbene (see Section I.2.I.2.4.2.6.2.), the metal carbenes generated with copper or rhodium catalysts display a selectivity for functional groups which are more nucleophilic than a double bond. Thus, no cyclopropanes are obtained from dialkylallylamines allyl sulfides -allyl dithioacetals , and allyl selenides under carbenoid conditions (copper or rhodium catalysts). 

The formation of substituted cyclopropane rings by the reaction of alkenes with Fischer carbenes has been known for some time [58]. More recently, cyclopropyl groups have been produced as parts of bicyclic and tricyclic ring systems by, formally, the reaction of Fischer carbenes with one equivalent of alkene and one equivalent of alkyne. Indeed, this reaction type proceeds through alkene trapping of a metal carbene generated in situ. The various methodologies that have been developed may be divided into three classes the intermolecular reaction of a,co-enynes with Fischer carbenes, the partially intramolecular reaction of Fischer carbene-tethered alkynes with alkenes, and the fully intramolecular reactions of Fischer carbene-tethered enynes. No fiilly intramolecular version of this reaction has been reported. 

Both olefin metathesis and ROMP require similar initiators and proceed by the same reaction mechanism. The initiating and propagating species are metal-alkylidene (carbene) complexes. The original initiators used for ROMP were two-component systems, composed of a halide or oxide of an early transition metal such as W, Mo Rh, or Ru with an alkylating agent (Lewis acid) such as ILtSn or RAICI2, which generate metal-carbenes in situ. These initiator... 

In one reported case, photochemical (instead of metal-catalyzed) carbene generation affords a higher yield (up to 43%) of benzodioxocin (134) (Scheme 49) careful selection of an appropriate base was required to avoid diversion of the reaction to other products <89JA1465>. 

In the case of the photochemical reaction, irradiation of diazomethane in the presence of cw-2-butene provides cw-l,2-di-methylcyclopropane with no detectable amount of the tram isomer (eq 45). This reaction is thought to proceed via a singlet carbene. However, if the same reaction is carried out via a triplet carbene, generated via triplet sensitization, then a 1.3 1 mixture of tram to cis dimethylcyclopropane is observed (eq 46). The yields in the photochemical reaction are typically lower than the metal-mediated processes, and are usually accoii5)anied by more side products. 

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