A Rh-Catalyzed C−H Insertion Reaction for the Oxidative Conversion of Carbamates to Oxazolidinones

Abstract

Vicinal amino alcohols are common structural units in both naturally occurring molecules and pharmaceutical agents. [1] These groups also appear as auxiliaries in asymmetric synthesis and in ligands for metal catalysts. [2, 3] The large and varied number of applications for b-hydroxy amines in synthetic, medicinal, materials, and coordination chemistry has fueled interest in the development of methods for their construction. [2a, 4] We have found a unique, metal-catalyzed CÀH insertion process that makes possible the preparation of such compounds from readily available carbamate starting materials [Eq. (1)]. This methodology utilizes catalytic quantities of a Rh II carboxylate complex and an inexpensive commercial oxidant, PhI(OAc) 2 . The product oxazolidinones are versatile, crystalline materials that can be opened under hydrolytic conditions to furnish 1,2-amino alcohols. [5,6] Transition metal promoted methods for the oxidative conversion of saturated hydrocarbons to amines or amine derivatives have limited precedence. [7,8] In one seminal example, both iron and rhodium catalysts were found to react with the iodoimine of 2,5-diisopropylbenzenesulfonamide to furnish a substituted benzisothiazoline product. [9] This reaction is believed to occur through intramolecular metal ± nitrene insertion into an isopropyl methine CÀH bond, though no mechanistic data has been offered in support of this claim. [10] More recently, reports of metal-catalyzed intermolecular allylic and benzylic C À H oxidation with PhI NSO 2 Ar reagents have been described. [7c±e,h±k] These processes are hampered, however, by the poor shelf life of the iodoimine starting materials, a restricted substrate profile, and the need to often employ large excesses of hydrocarbon substrates.We wished to explore the use of simple carbamate materials as precursors for the synthesis of substituted oxazolidinones.The crystalline indanol derivative 2 used for our initial studies was afforded easily upon treatment of alcohol 1 with CCl 3 C(O)NCO followed by K 2 CO 3 /MeOH (Scheme 1). [11] O HN O OR 86% yield 1: R = H 2: R = CONH 2 a b 3 Scheme 1. a) CCl 3 C(O)NCO; K 2 CO 3 /MeOH; b) 5 mol % [Rh 2 (OAc) 4 ], PhI(OAc) 2 , MgO, CH 2 Cl 2 , 408C, 12 hr.Control experiments indicate that 2 does not react with PhI(OAc) 2 after b 10 hr at 40 8C. [12] We were pleased to find, however, that a stirred suspension of 2, PhI(OAc) 2 , and 5 mol % [Rh 2 (OAc) 4 ] at 258C produced $ 15 % of the desired oxazolidinone 3. Analysis of the unpurified reaction mixture by 1 HNMR spectroscopy indicated that the sample comprised mostly starting material 2. Subsequent studies demonstrated that the conversion of 2 into 3 could be improved slightly by warming the mixture of reactants to 40 8C, an observation that intimated a possible problem with slow catalyst turnover. Following a series of control experiments, we concluded that AcOH, generated as a by-product from PhI(OAc) 2 , reduced the catalytic activity of [Rh 2 (OAc) 4 ]. The need to scavenge AcOH from the reaction mixture p...

Dirhodium-catalyzed C-H arene amination using hydroxylamines

“…The influence of ligands and counter ions on the reactivity of organometallics is well precedented (43, 44). However, examples of such dramatic bifurcation of the reaction manifold are rare and warrant closer study to understand the energetics and full synthetic potential of this metalloid-nitrogen umpolung for direct arene aminations.…”

Selective Intermolecular Amination of CH Bonds at Tertiary Carbon Centers

“…[9] Of these, the sulfamate prepared from 2,6-difluorophenol, DfsNH 2 , has proven optimal. Empirical studies reveal that the inclusion of both MgO and 5 Å molecular sieves further improves catalyst TONs, as does an initial substrate concentration of 1.0 M. [10–12] The reaction mixture appears as a green slurry from which product 2 can be isolated in 57% yield (12 h). [13,14] …”

Capturing fleeting intermediates in a catalytic C–H amination reaction cycle

“…1. Sulfamate 2 and iodine oxidant 3 condense to form iminoiodinane 4 (14,15). The iminoiodinane is a ligand for Rh 2 (esp) 2 , which react to generate [Rh 2 (esp) 2 ]•PhINSO 2 OR 5; subsequent loss of iodobenzene (PhI) furnishes nitrenoid 6.…”