Rhodium‐Catalyzed Enantioselective Silylation of Cyclopropyl C−H Bonds

Abstract

We describe an enantioseleclive silylation of cyclopropanes catalyzed by a rhodium precursor and the bisphosphine (S)-DTBM-SEGPHOS. (Hydrido)silyl ethers, generated in situ by the dehydrogenative silylation of cyclopropylmethanols with diethylsilane, undergo asymmetric, intramolecular silylation of cyclopropyl C-H bonds in high yields with high enantiomeric excesses in the presence of the rhodium catalyst. The resulting enantioenriched oxasilolanes are suitable substrates for Tamao-Fleming oxidation to form cyclopropanols with conservation of the ee from the C-H bond silylation. Preliminary mechanistic data suggest that C-H cleavage is likely to be the turnover-limiting and enantioselectivity-determining step. Graphical Abstract(Hydrido)silyl ethers, generated in situ by the dehydrogenative silylation of cyclopropylmethanols with diethylsilane, undergo asymmetric, intramolecular silylation of cyclopropyl C-H bonds in high yields with high enantiomeric excesses in the presence of a rhodium catalyst. The silylation products are suitable substrates for Tamao-Fleming oxidation to form cyclopropanols with conservation of the ee from the C-H bond silylation.Keywords asymmetric catalysis; C-H activation; cyclopropane; rhodium; silylation The functionalization of C-H bonds with boranes and silanes has been studied intensively, due to the high regioselectivity of these processes for sterically accessible C-H bonds and widespread utility of the products. [1,2] However, the development of enantioselective variants of these reactions, particularly enantioselective functionalization of alkyl C-H bonds, has been limited (Scheme 1). [3][4][5] Kuninobu, Murai and Takai reported the Correspondence to: John F. Hartwig, jhartwig@berkeley.edu. Supporting information for this article is given via a link at the end of the document. HHS Public Access Author ManuscriptAuthor Manuscript Author ManuscriptAuthor Manuscript asymmetric silylation of a C-H bond to generate a stereogenic silicon center with up-to 88% enantiomeric excess (ee) (Scheme 1A). [6,7] Shibata, He, Murai and Takai independently reported the synthesis of planar chiral compounds with moderate to high enantioselectivities by asymmetric C-H silylation of ferrocenes. [8][9][10] Recently, we reported an enantioselective silylation of aryl C-H bonds to form enantioenriched benzoxasilole products with up-to 99% ee. [11] Although these reactions can occur with high enantioselectivity, they are limited to the functionalization of aryl C-H bonds. The only published set of enantioselective silylations of alkyl C-H bonds occurs with low ee (37-40% ee) and with limited scope (Scheme 1B). [12] To create the first silylations of alkyl C-H bonds that occur with high enantioselectivity, we investigated systems for the reactions of cyclopropanes. C-H bonds of cyclopropanes are more reactive than sp 3 C-H bonds of unstrained rings or alkyl chains, [13] and the rigid conformation of a cyclopropane could allow for high stereoselectivity. Yu and co-workers reported enantioselective...

Rhodium‐Catalyzed Silylative and Germylative Cyclization with Dehydrogenation Leading to 9‐Sila‐ and 9‐Germafluorenes: A Combined Experimental and Computational Mechanistic Study

“…Reaction of hydrosilane containing am ethyl group ortho to the silylphenyl group afforded am ixture of 9-silafluorene 2h and 9,10-dihydro-9-silaphenanthrene 7 in 8% and 31 %y ield, respectively (Scheme3). [12] Addition of 3,3-dimethyl-1-butene was again effective for this dehydrogenative silylation.S imilar selectivity was observedf or dehydrogenative cyclization of the corresponding biarylgermane 3h,i nw hich 9,10-dihydro-9-germaphenanthrene 8 was obtained as am ajor product along with 9-germafluorene 4h.T hese resultsd emonstrate that dehydrogenative silylation and germylation of the C(sp 3 )ÀH bonds occurred preferentially over the aryl C(sp 2 )ÀHb onds. This outcomei su nique, because dehydrogenative functionalization generally favors C(sp 2 )ÀHb onds under neutralc onditions, and selectivef unctionalization of C(sp 3 )ÀHb onds remains difficult.…”

“…These resultsp rovide ar ationalef or the experimental observations that most of the reported iridium-catalyzed dehydrogenative silylations require hydrogen acceptors. [11][12][13] Iridium catalysis with ah ydrogen acceptor mayb es uitable for dehydrogenative silylationo fC ÀHb onds, in which oxidative addition is includeda sadifficult step, but not effective for the current oxidant-free intramolecular system, as shown in Table 1, entry 3.…”

“…[9] Despite these rapid experimental advances, the reactionm echanism and the reason why the reactionp roceeds without oxidant, have not been fully elucidated. Experimental observations that the choice of oxidant (hydrogen acceptor) was crucial in the followings imilart ypes of dehydrogenative silylation were especially interesting:i )iridium-catalyzed intramolecular silylation of CÀHb onds, [11] ii)rhodium-catalyzed intramolecular silylation of C(sp 3 )ÀHb onds, [12] and iii)rhodium-or iridium-catalyzed intermolecular silylation of CÀHb onds. [13] The present study describes experimental and computational results relatedt ot he uniqueo xidant-free dehydrogenative silylationo fC (sp 2 )ÀHb onds.…”

Enantioselective C(sp 3 )‒H bond activation by chiral transition metal catalysts

“…Several complementary approaches to the aforementioned enantioselective Pd(II)/Pd(0) or Pd(II)/Pd(IV) catalyses for C(sp 3 )–H desymmetrization have been developed, including enantioselective Pd(0)/Pd(II) catalyses (32–35) as well as Rh(I)/Rh(III) (36,37) catalyses. The only examples of these point desymmetrization are intramolecular ( i.e.…”

PdII‐Catalyzed Enantioselective C(sp3)−H Activation/Cross‐Coupling Reactions of Free Carboxylic Acids

“…With our previously developed b-C À Ha rylation of free cyclopropyl carboxylic acid with aryl iodides in mind, [7] we began our study by investigating the reactivity of cyclopropanecarboxylic acid under Pd II /Pd 0 catalysis. [8,9] Initially we focused on the CÀHcross-coupling reactions with phenylboronic acid pinacol ester using various types of bidentate chiral ligands (Table 1). While 11 %yield was obtained in the absence of ligand, we were pleased to observe that monoprotected aminoethyl amine (MPAAM) ligand (L1)provided the desired arylated product in 38 %yield with 96:4 er.…”