Of carbenoids

Other potential synthetic routes to these unsaturated aziridine derivatives which involve the addition of nitrenes to allenes <75JOC224), carbenes to imines with subsequent hydrolysis <67JA362), and of carbenoid species to ketenimines <76TL1317,79TL559) have been investigated but are collectively of little or no preparative value. 

At 22 °C the overall second-order coefficient for reductions by Fe(n) and Cu(I) are, respectively, 4x10 and 5xl0 l.mole .sec Products in the presence of olefins demonstrate unequivocally the intermediacy of carbenoid transients, and a complex mechanism is put forward, viz. 

An interesting application of carbenoid O/H insertion is the synthesis of macrocyclic oxacrown ethers 337 from a,a>-diazoketones 336 and oligoethylene glycols 323). 

The known examples of carbenoid insertion into an S—H bond have been supplemented by the Rh2(OAc)4-catalyzed synthesis of a-phenylthioketones from a-diazoketones and thiophenol 327). By this method, a number of primary and secondary acyclic a-diazoketones, ethyl diazoacetate and cyclic diazoketones such as 2-diazocyclopentanone, 2-diazo-6-methylcyclohexanone and 2-diazocyclohepta-none were converted at room temperature in good to high yield. 

Reactions of carbenoids with 4-thio-substituted 2-azetidinones have attracted much interest recently. Insertion of the carbene unit derived from diazomalonic esters 297-34°> or ethyl diazo(diethoxyphosphoryl)acetate 340 into the C4—S bond of simple P-lactams 353 and 354 took place irrespective of whether a N—H or a N—R... 

The dihalocarbene method was expanded in scope and improved in yield by the introduction of carbenoids of several types. Thus, (dichloro-bromomethyl) phenyl mercury reacted with diaryl acetylenes giving diaryl cyclopropenones in high yields (60—... 

Activation of a C-H bond requires a metallocarbenoid of suitable reactivity and electrophilicity.105-115 Most of the early literature on metal-catalyzed carbenoid reactions used copper complexes as the catalysts.46,116 Several chiral complexes with Ce-symmetric ligands have been explored for selective C-H insertion in the last decade.117-127 However, only a few isolated cases have been reported of impressive asymmetric induction in copper-catalyzed C-H insertion reactions.118,124 The scope of carbenoid-induced C-H insertion expanded greatly with the introduction of dirhodium complexes as catalysts. Building on initial findings from achiral catalysts, four types of chiral rhodium(n) complexes have been developed for enantioselective catalysis in C-H activation reactions. They are rhodium(n) carboxylates, rhodium(n) carboxamidates, rhodium(n) phosphates, and < // < -metallated arylphosphine rhodium(n) complexes. 

Figure 9 Classification of carbenoid intermediates and common precursors.

Rhodium(n) carboxamidates are clearly superior to all other types of catalysts in effecting highly chemo-, regio-, diastereo-, and enantioselective intramolecular C-H activation reactions of carbenoids derived from diazoacetates. Specifically, Rh2(4Y-MPPIM)4 is the catalyst of choice for C-H activation reactions of simple primary and secondary alkyl diazoacetates. Likewise, Rh2(4Y-MACIM)4 thus far has been the most successful catalyst with tertiary alkyl diazoacetates, whereas for primary acceptor-substituted diazoacetates with a pendant olefin side chain, Rh2(4A-MEOX)4 has proved to be highly selective. 

In an important communication of 1989, Negishi reported [37] the first insertions of a-and y-haloorganolithium reagents into acyclic zirconocene chlorides. Recently, this work has been extended to a wide variety of carbenoids and organozirconium species, including zirconacycles, to provide a variety of new synthetic methods. These are described below. 

The most extensively studied application of carbenoid insertion into organozirconocene species is the insertion of allyl carbenoids into zirconacycles and subsequent elaboration of the thus formed allylzirconocenes with electrophiles (Schemes 3.24—3.26) [48,53,55-60],... 

For application in organic synthesis, the regiochemistry of insertion of carbenoids into un-symmetrical zirconacydes needs to be predictable. In the case of insertion into mono- and bicydic zirconacydopentenes where there is an wide variety of metal carbenoids insert selectively into the zirconium—alkyl bond [48,59,86], For more complex systems, the regiocon-trol has only been studied for the insertion of lithium chloroallylides (as in Section 3.3.2) [60]. Representative examples of regiocontrol relating to the insertion of lithium chloroal-lylide are shown in Fig. 3.2. 

Scheme 3.39. Alternative explanation for the regiochemistry of carbenoid insertion.

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