Asymmetric C—H Bond Insertion Reactions

It has been recognized for over 70 years that C—H bond functionalization can be realized through carbene insertion reactions. In reeent years, many outstanding works ineluding asymmetrie reactions have appeared in this area  

Considering metal earbenoid-indueed C—H bond insertions, there exists a general pattern, as shown in Seheme 1.1. The catalytic cycle is initiated by a metal complex via the deeomposition of diverse carbene precursors (such as diazo compounds) to deliver a transient metal earbenoid intermediate in situ. Subsequently, the highly reactive metal earbenoid intermediate inserts into the C—H bond to afford the corresponding product and readily regenerates the metal complex to complete the catalytie eycle. Note that the metal atom is not thought to interact with the C—H bond directly. Moreover, since the transient metal earbenoid intermediate is highly reactive, the reaction conditions are typically mild and pH neutral, which renders this method 

Rh and Cu complexes are commonly employed in metal carbenoid-involved asymmetric C—H bond functionalization while chiral catalysts based on Ir, Ru, and Fe as well as Lewis acids came into this area recently. This section aims to introduce the recent developments in asymmetric C—H bond functionalization achieved by metal carbenoids. 

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Asymmetric C—H Bond Insertion Reactions Acceptor carbenoid H... 

Apart from the utilization of aryl- and vinyl-diazoacetates that can achieve the moderate to high chemo-, regio-, and enantioselectivity in intermolecular asymmetric C—H bond insertion reactions, Af-sulfonyl-l,2,3-triazole 11 was found to be able to function as an alternative carbene precursor for diverse transformations (Scheme 1.4). One advantage for using the N-sulfonyl-1,2,3-triazole is that it could be easily prepared by the Cu -catalyzed azide-alkyne cycloaddition (CuAAC) reaction, and in some cases, delicately designed reactions can be conducted in a one-pot procedure starting from alkynes and sulfonyl azides. Moreover, since there exists an inherent equilibrium... 

Scheme 1.5 Rh-catalyzed asymmetric C—H bond insertion reactions of azavinyl earbenoids reported by Fokin.

Scheme 1.7 Asymmetric C—H bond insertion reactions of dirhodium carbenoids reported by Davies.

Recently, as a continuing interest in the synthetic application of a-alkyl-a-diazo ester 28, Hashimoto and co-workers reported the first Rh-catalyzed intermolecular asymmetric C—H bond insertion reaction of a-alkyl-a-diazo ester (Scheme l.S). " Despite only moderate yields and ee obtained by employing Rh2(S-TFPTTL)4 or Rh2(iS -TCPTTL)4, excellent results were obtained in a previous report on the asymmetric cyclopropanation of alkyne. ... 

Apart from the extensively documented dirhodium catalysts, several ehiral Ir complexes have lately also been shown to be catalytically efficient in the asymmetric C—H bond insertion reactions of metal carbenoids and they offer eom-plementary reaetivity profiles. In general, 1,4-cyclohexadienes and THF are two commonly used model substrates. Several groups, including Katsuki, " Che, and Musaev, Davies, and Blakey, have realized the intermoleeular C—H bond insertion reaetion of 1,4-cyclohexadienes and THF by diverse ehiral Ir complexes (Figure 1.5). 

Che and co-workers expanded the scope of the Ir-porphyrin complex catalyzed asymmetric C—H bond insertion reaction to intramolecular variants. A catalytic amount of (+)-C5 (L = H2O or solvent) converted an array of benzyl a-aryl-a-diazo esters 91 into ds-p-lactones via intramolecular asymmetric C—H bond insertion reaction in good yields (up to 87%) and enantioselectivity (up to 78% ee) (Scheme 1.30). It is noteworthy that common dirhodium car-boxylate catalysts such as Rh2(S -PTAD)4 or Rh2(S -MEPY)4 could not catalyze this reaction effectively. 

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