Isotope Effects and the Nature of Selectivity in Rhodium-Catalyzed Cyclopropanations

Abstract

The mechanism of the dirhodium tetracarboxylate catalyzed cyclopropanation of alkenes with both unsubstituted diazoacetates and vinyl- and phenyldiazoacetates was studied by a combination of (13)C kinetic isotope effects and density functional theory calculations. The cyclopropanation of styrene with methyl phenyldiazoacetate catalyzed by Rh(2)(octanoate)(4) exhibits a substantial (13)C isotope effect (1.024) at the terminal olefinic carbon and a smaller isotope effect (1.003-1.004) at the internal olefinic carbon. This is consistent with a highly asynchronous cyclopropanation process. Very similar isotope effects were observed in a bisrhodium tetrakis[(S)-N-(dodecylbenzenesulfonyl)prolinate] (Rh(2)(S-DOSP)(4) catalyzed reaction, suggesting that the chiral catalyst engages in a very similar cyclopropanation transition-state geometry. Cyclopropanation with ethyl diazoacetate was concluded to involve an earlier transition state, based on a smaller terminal olefinic isotope effect (1.012-1.015). Density functional theory calculations (B3LYP) predict a reaction pathway involving complexation of the diazoesters to rhodium, loss of N(2) to afford a rhodium carbenoid, and an asynchronous but concerted cyclopropanation transition state. The isotope effects predicted for reaction of a phenyl-substituted rhodium carbenoid with styrene match within the error of the experimental values, supporting the accuracy of the theoretical calculations and the rhodium carbenoid mechanism. The accuracy of the calculations is additionally supported by excellent predictions of reaction barriers, stereoselectivity, and reactivity trends. The nature of alkene selectivity and diastereoselectivity effects in these reactions is discussed, and a new model for enantioselectivity in Rh(2)(S-DOSP)(4)-catalyzed cyclopropanations is presented.

Rh-Catalyzed Intermolecular Cyclopropanation with α-Alkyl-α-diazoesters: Catalyst-Dependent Chemo- and Diastereoselectivity

“…16 Our observations are consistent with Davies' hypothesis, as the Rh 2 Piv 4 catalyzed reaction of styrene with ethyl α-diazopropionate proceeds with low diastereoselectivity relative to the analogous reactions of styrene with α-aryl or α-styryl diazoesters. 13…”

3,3’’-Bis(saccharin-6-ylmethyl)-1,1’:3’,1’’-terphenyl – Precursor of A New Tetradendate Bis-bridging Ligand

“…The terphenyl/saccharin conjugate 15 was obtained by Suzuki-Miyaura coupling of dibromide 9 and either dioxaborolane 13 or boronic acid 14 (Scheme 3). With the boronic acid and standard reaction conditions (Pd(PPh 3 ) 4 , Na 2 CO 3 , toluene/EtOH/H 2 O) a significantly better yield of 15 (76 %) was obtained. N-Deprotection of 15 was achieved by transfer hydrogenation [30] and furnished the ligand precursor H 2 tpsac (7).…”

“…Dinuclear rhodium(II,II) carboxylates and amidates of the type Rh 2 (µ-L) 4 (L = bidentate ligand) are efficient catalysts for intramolecular and intermolecular carbenoid reactions of diazo compounds [1]. While experimental evidence and computational results nowadays corroborate the mechanistic hypotheses of shortlived rhodium-carbene intermediates and their chemical and stereochemical mode of interaction with substrate molecules, it is still not clear which role is played by ligand dynamics in the catalytic process and to which extent it affects the catalyst's lifetime under the reaction conditions.…”

“…While experimental evidence and computational results nowadays corroborate the mechanistic hypotheses of shortlived rhodium-carbene intermediates and their chemical and stereochemical mode of interaction with substrate molecules, it is still not clear which role is played by ligand dynamics in the catalytic process and to which extent it affects the catalyst's lifetime under the reaction conditions. The mentioned complexes Rh 2 (µ-L) 4 have a paddlewheel structure with the chelating ligands in equatorial positions; in a rhodium-carbene complex, the carbene ligand occupies the available axial coordination site at one rhodium center, similar to the coordination of neutral Lewis base ligands such as water, amines and nitriles (for the first X-ray crystal structure determination of a Rh 2 (tBuCOO) 4 complex bearing an axial NHC ligand, see ref. [2]; for a related Ru(I,I)-NHC complex, see ref.…”

“…We have recently synthesized a variety of dinuclear tetracarbonyldiruthenium(I,I) carboxylate and amidate complexes, Ru 2 (CO) 4 (µ-L) 2 , and have studied them as alternative catalysts for carbene transfer reactions with diazo compounds [9 -13]. These diruthenium complexes have the typical sawhorse structure [14] with the two bidentate ligands in cis-configuration.…”