Asymmetric NH Insertion Reaction Cooperatively Catalyzed by Rhodium and Chiral Spiro Phosphoric Acids

Abstract

Nitrogen-containing organic compounds, such as a-amino acids and alkaloids, are important biologically active compounds, thus the development of efficient and enantioselective methods for the construction of carbon-nitrogen bonds is a fundamental goal in modern organic synthesis.[1] Transitionmetal-catalyzed carbene insertion into N À H bonds is one of the most efficient methods to construct carbon-nitrogen bonds [2] and the development of asymmetric versions of the NÀH insertion reaction has attracted considerable attention. [3] In initial studies, chiral dirhodium catalysts were tested in intramolecular [4] and intermolecular [5] NÀH insertion reactions, however, only low to modest enantioselectivities (< 50 % ee) were achieved. Since these reports, other transition metals including copper and silver have been used as catalysts, and gave enantioselectivities up to 48 % ee.[6]Recently, we reported a highly enantioselective NÀH insertion reaction (up to 98 % ee) using a copper complex with chiral spiro bisoxazoline ligands.[7] Subsequently, two other types of chiral copper catalysts have been developed, one with a planar chiral bipyridine ligand [8] and the other with a binolderivative ligand, [9] and both of these catalysts give high enantioselectivities in NÀH insertion reactions.Although progress on copper-catalyzed asymmetric NÀH insertion reactions has been substantial, they still have serious limitations. For instance, all the copper-catalyzed N À H insertion reactions require high catalyst loading (5-10 mol %) for satisfactory yields and enantioselectivities, thus more-efficient chiral catalysts are highly desirable. Because the activity of dirhodium(II) catalysts is usually superior to that of copper catalysts in nonenantioselective NÀ H insertion reactions, [10] the possibility of using dirhodium catalysts to achieve highly enantioselective N À H insertion reactions is an intriguing one. Recently, Saito et al. [11] reported that dirhodium(II) carboxylates and cinchona alkaloids cooperatively catalyze the asymmetric NÀH insertion reactions of a-diazo-a-arylacetates with anilines. The combined catalysts exhibit excellent reactivity but only modest enantioselectivity (up to 71 % ee). It is generally accepted that the rhodium-catalyzed N À H insertion most likely proceeds via an ylide intermediate (Scheme 1 A).[2a] We speculated that the subsequent protontransfer step could be facilitated by a chiral phosphoric acid [12] species via a seven-membered-ring transition state, and that, consequently, chiral induction could be accomplished in this step (Scheme 1 B). The groups of Yu [13] and Platz [14] have reported that either water or alcohols can assist proton transfer in OÀH insertion reactions, as indicated by density functional theory calculations and ultrafast time-resolved IR spectroscopy studies. These studies stimulated our interest in exploring asymmetric N À H insertion in the presence of a proton-transfer catalyst. As part of our ongoing work on the development of asymmetric carbene insertion reaction...

Mechanistic Insight into Asymmetric N–H Insertion Cooperatively Catalyzed by a Dirhodium Compound and a Spiro Chiral Phosphoric Acid

“…The reaction depicted in Scheme 2 is selected as our subject. 5 In light of our calculations, the formation of the ammonium ylides (B and C) is disfavored and the [1,2]-proton shift for both species suffers from the inaccessible overall barrier to give the N−H insertion product at room temperature. On the other hand, the formation of the enamine intermediate is more favorable kinetically as well as thermodynamically.…”

Cooperation of Non‐covalent Interactions and Coordination in Catalysis

“…An asymmetric N─H insertion reaction of methyl α-diazo-α-phenylacetate into the N─H bond of tert-butyl carbamate (BocNH 2 ) cooperatively catalyzed by dirhodium(II) carboxylates and chiral spiro phosphoric acids (SPAs) allows to reach high yields and enantioselectivities [9]. An asymmetric N─H insertion reaction of methyl α-diazo-α-phenylacetate into the N─H bond of tert-butyl carbamate (BocNH 2 ) cooperatively catalyzed by dirhodium(II) carboxylates and chiral spiro phosphoric acids (SPAs) allows to reach high yields and enantioselectivities [9].…”

“…Proposed mechanism of insertion of carbene from methyl α-diazo-α-phenylacetate into BocNH 2 [9]. deprotonate the isocyanoacetate.…”

Chiral Bis(imidazolidine)‐Derived NCN Pincer Rh Complex for Catalytic Asymmetric Mannich Reaction of Malononitrile with N‐Boc Imines

“…Eur.J.2015, 21,10671 -10675 www.chemeurj.org synthetic methodology for natural and unnaturala mino acids. [16] Ap ossible mechanism for the [tBu-PhBidine-Rh(OAc) 2 ]-catalyzed asymmetricM annich reaction is shown in Scheme 3. ESI-MS analysiso nt he mixture of [tBu-PhBidine-Rh(OAc) 2 ]a nd malononitrile gave an ew ion peak at m/z = 1043.3766, corresponding to …”