Diastereoselective intermolecular O H insertions by Cu(II)-mediated carbenoids derived from phenyldiazoacetamide

The diastereoselective insertion into carboxylic O H bonds was investigated with camphorsultam as a chiral auxiliary, and moderate to good selectivity was achieved. © 2001 Elsevier Science Ltd. All rights reserved. Along with the well established intramolecular C H insertion reactions by Rh(II)-mediated carbenoids, there has been considerable attention directed to the corresponding insertion into polar X H bonds (X=N, O, S, etc.) by metal carbenes. The X H bonds (X=N, O, S, etc.) are generally more reactive than the corresponding C H bond toward metal carbenes, so in contrast to the C H insertion in which only the intramolecular reaction gives reasonable selectivity, the intermolecular X H insertion in many cases is highly selective and thus synthetically useful. Intermolecular O H insertions by carbenoids have been investigated by several groups, the results suggest that this type of insertion is highly efficient. The O H insertion by a metal carbene derived from -diazo carbonyl compounds gives -hydroxy acid derivatives, which are found as structural units in many natural products, as well as being useful synthetic building blocks. The asymmetric version of Rh(II)-mediated carbenoid insertion into alcoholic O H bonds was exploited with the aid of a chiral auxiliary (Scheme 1). However, the diastereoselectivity so far obtained is still low to moderately high. In connection with our interest in the synthetic application of -diazo carbonyl compounds, we have investigated the Cu(II) complexmediated metal carbene insertion into the O H bonds of carboxylic acids in the presence of a chiral auxiliary. We found that reasonably high diastereoselectivity can be obtained in this case. The scope and limitation of this diastereoselective O H insertion reaction is presented in this communication. Oppolzer’s camphorsultam was employed as a chiral auxiliary in this investigation. The phenyldiazoacetyl derivative 1 was prepared according to the literature procedure through a tosylhydrazone. This diazo compound was decomposed with a catalytic amount of Cu(acac)2 in the presence of 2 equiv. of various acids in dry benzene (Scheme 2). The diastereoselectivity of the product was analyzed using 400 MHz NMR spectroscopy. The results are collected in Table 1. As shown in Table 1, it is obvious that the carboxylic acid structure has a marked influence over the diastereoselectivity. Sterically bulkier acids enhance the diastereoselectivity. On the other hand, the reaction temperature can also greatly affect the diastereoselectivity: the data show that low temperatures generally improve the selectivity. However, when the reaction was run below 55°C, it took a very long time for the reaction to reach completion. The insertion with 2,2dimethylpropanoic acid at 60°C gave a diastereoselectivity of 95:5, which is the highest diastereoselectivity achieved in O H insertion reactions by carbenoids. Since it is well known that the nature of the transition metal catalyst can exert a significant influence over the regioand chemoselectivity, as well as the stereoselecScheme 1. * Corresponding author. 0040-4039/01/$ see front matter © 2001 Elsevier Science Ltd. All rights reserved. PII: S0040 -4039 (01 )01832 -9