Highly Selective Metal Catalysts for Intermolecular Carbenoid Insertion into Primary CH Bonds and Enantioselective CC Bond Formation

Abstract

Direct functionalization of CÀH bonds is an appealing strategy in organic synthesis [1] but its practical application has so far been difficult to realize. The selective functionalization of primary C À H bonds of alkanes that also contain secondary and/or tertiary C À H bonds is a great challenge, as CÀH bond energy follows an order primary > secondary > tertiary. [1c,d] In seminal works by Bergman, [1b] Jones, [1c] and their respective co-workers, stoichiometric reactions of alkanes with [Cp*(Me 3 P)M] (Cp* = C 5 Me 5 ; M = Rh, Ir) resulted in the formation of C À M bonds by selective activation of primary C À H bonds. Subsequent work by Hartwig and coworkers [1g,i, 2] demonstrated C À B bond formation by stoichiometric and catalytic functionalization of primary CÀH bonds mediated by tungsten, rhodium, or ruthenium complexes. The high selectivity for primary CÀH bond functionalization in these C À M or C À B bond-formation reactions (Scheme S1 in the Supporting Information) is considered to result from kinetic factors or steric interaction between the metal complexes and alkanes. [1i, 3] A well-established process in CÀC bond formation by direct CÀH bond functionalization is the metal-catalyzed intra-and intermolecular carbenoid insertion into C À H bonds, with diazo compounds as the carbene source. [1o, 4] These catalytic C À C bond-formation reactions generally feature lower selectivity for primary CÀH bonds than for secondary and tertiary CÀH bonds. For example, a selectivity order of primary < secondary < tertiary C À H bonds has been observed for the extensively investigated carbene insertion catalyzed by rhodium complexes, [4,5] possibly because of the electron density order of primary < secondary < tertiary CÀH bonds, which renders primary CÀH bonds the least susceptible to attack by electrophilic rhodium-carbene intermediates.[5] By manipulating the steric or electronic properties of the metal catalysts, a selectivity for primary C À H bonds of alkanes comparable to that for secondary or tertiary C À H bonds was observed, [6] with the highest primary/secondary and primary/tertiary ratio per CÀH bond being 1.17:1.0[6b] and 1.0:0.9, [6c] respectively. Herein we report a highly selective primary CÀH bond functionalization by metal-catalyzed carbenoid insertion into the C À H bonds of alkanes (Scheme 1), which features a primary/secondary selectivity (that is, the primary/secondary ratio per C À H bond) of up to 11.4:1. We have also accomplished highly enantioselective functionalization of secondary C À H bonds with ee values of up to 93 % and product turnovers up to 6100 through metal-mediated carbenoid CÀH bond insertion reactions.Our studies in this work were inspired by previous work from the research groups of Callot [6a,b] and Suslick. [7] In the 1980s, Callot and co-workers reported that the primary C À H bond selectivity for the reaction of linear alkanes with ethyl diazoacetate (N 2 CHCO 2 Et, EDA) catalyzed by [Rh(por)I] (H 2 (por) = meso-tetraarylporphyrin) increases with the size o...

Highly thermally stable heterogeneous catalysts: study of 0D and 3D porphyrinic MOFs

“…19,20 In this sense, porphyrin-based MOFs are reporting great results, [21][22][23] since Suslick et al reported the first catalytic activity of a porphyrinic coordination polymer with open structure. 24 In the last years, porphyrinic complexes of iron, 25 cobalt, 26 ruthenium, 27 rhodium, 28 among others, are known in literature to catalyze chemical reactions like, for example, olefin cyclopropanation and X-H (X = C, N, Si) bond insertion with high efficiency and selectivity. For instance, Rh-porphyrin complexes provide cyclopropanation and C-H primary insertion products with extraordinary selectivity.…”

“…For instance, Rh-porphyrin complexes provide cyclopropanation and C-H primary insertion products with extraordinary selectivity. 28 Further, Feand Ru-porphyrins can furnish the N-H insertion of ammonia 25 and peptides containing an N-terminal amine, 27 respectively.…”

Alkane Catalytic Functionalization by Carbene or Nitrene Insertion Reactions

“…As shown in Scheme 6.17, ca 90 % ee were achieved with cyclohexane (secondary C-H) and adamantane (tertiary C-H), whereas only 60 % ee was reached with 2-methylbutane. Ten years later, a rhodium- porphyrin catalyst [70] (II, Scheme 6.16) was described to give similar degrees of enantioselection, as well as the already mentioned high regioselection toward primary sites. Thus, hexane or 2,2-dimethylbutane were preferentially functionalized in the primary sites with the subsequent generation of the stereocenter.…”

Carbenoid insertions into benzylic C–H bonds with heterogeneous copper catalysts

“…As expected from the reactivity order, the primary benzylic position of toluene was completely inactive to insertion, in contrast with Rh catalysts. 20,24,25 …”