Carbenoids formation

In contrast to the extensive body of work on the preparation of these zinc carbenoids, few investigations are on record concerning the mechanism of the Furu-kawa method for carbenoid formation. Two limiting mechanisms can be envisioned - a concerted metathesis via a four-centered transition structure or a stepwise radical cleavage-recombination (Scheme 3.11). 

It has been widely accepted that the carbene-transfer reaction using a diazo compound and a transition metal complex proceeds via the corresponding metal carbenoid species. Nishiyama et al. characterized spectroscopically the structure of the carbenoid intermediate that underwent the desired cyclopropanation with high enantio- and diastereoselectivity, derived from (91).254,255 They also isolated a stable dicarbonylcarbene complex and demonstrated by X-ray analysis that the carbene moiety of the complex was almost parallel in the Cl—Ru—Cl plane and perpendicular to the pybox plane (vide infra).255 These results suggest that the rate-determining step of metal-catalyzed cyclopropanation is not carbenoid formation, but the carbene-transfer reaction.254... 

The detailed mechanism of transition metal-catalyzed cyclopropanation using diazo compounds as a carbene source is still covered by clouds of controversy, but it is generally accepted that the reaction proceeds through metal-carbenoid complexes,17-21 and the valency of the metal ions (M) changes with carbenoid formation (Scheme 85). 

In addition to insertions into polar X-H bonds by means of ylide intermediates, carbe-noids are capable of inserting into nonpolar bonds such as Si-H and C-H. The Si-H insertion by vinylcarbenoids has been developed as a novel method for the synthesis of allylsilanes 166 and 167 of defined geometry as illustrated in Eqs. (17) and (18) [28]. The alkene geometry of the vinyldiazoacetate is not altered during carbenoid formation or the subsequent Si-H insertion. 

Theoretical calculations (B3LYP) gave predicted isotope effects consistent with experimental effects. Modelled reaction pathway involves complexation of the diazoesters to rhodium, loss of N2 and rhodium carbenoid formation and formation of asynchronous but concerted cyclopropanation transition state. 

In 1996, Mioskowski and co-workers expanded on this second observation to advance the classical reductive alkylation chemistry of epoxides first reported by Crandall and Lin in 1967 (Scheme 47, Equation 6) <1967JA4526, 1967JA4527, 19830R345>. Mioskowski and co-workers proposed a similar pathway for the formation of cyclopentenol 102 from methoxy-substituted cyclopentene oxide 101 lithiation, carbenoid formation, insertion into the excess organolithium, followed, in this case, by LiOMe elimination (rather than Li20) (Scheme 47, Equation 7) <1996CC549>. 

The phorbol skeleton to yield 61 was also assembled in one step via rhodium catalyzed carbenoid formation, Eq. 42 [71]. 

The intramolecular cyclopropanation of several unsaturated diazo carbonyl compounds83 is most efficiently catalyzed by the Aratani complex (A)-4. Thus, 1-diazo-5-hexen-2-one is converted into (15",5i )-2-oxobicyclo[3.1.0]hexane with 77% ee, An interesting aspect of this study is the activation of the catalyst by bis(2-methylpropyl)aluminum hydride, which reduces the copper(II) to give a copper complex. Other unsaturated diazoketones with the / -complex 4 gave inferior results and with a-diazo /i-oxo esters, which require higher temperatures for carbenoid formation, the enantiomeric excesses were close to zero. 

Conjugated enynes possess several of the same transition metal binding modes exhibited by their diyne counterparts, including Jt-coordination, a-carbenoid formation, and a/jt metal complexation (Scheme 35). In some cases, these constructs are very stable and can be isolated, but they are frequently transient structures in which the metal ion acts as a catalyst for enyne cycloisomerisation and ligand transformation reactions. 

An efficient desymmetrization in me50-epoxides of type 209 by 5ec-alkyllith-ium/(-)-sparteine was found by Hodgson et al. [see Eq. (66)] [123-125]. The intermediate lithiooxirane 210 usually undergoes carbenoid formation and intramolecular C-H insertion reactions (see Hodgson et al, in this volume) however, very recently it could be trapped by external electrophiles with stereoretention at low temperatures [126]. 

Harada T, Katsuhira T, Oku A (1992) Stereochemistry in carbenoid formation by bromine/ lithium and bromine/zinc exchange reactions of 1,1-dibromoalkenes higher reactivity of the sterically more hindered bromine atom. J Org Chem 57 5805-5807. doi 10.1021/jo00048a002... 

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