Rhodium-Catalyzed Asymmetric Ring Opening Reactions of Oxabicyclic Alkenes:  Application of Halide Effects in the Development of a General Process

Abstract

We have demonstrated halide effects in the rhodium-catalyzed asymmetric ring opening reaction of oxabicyclic alkenes. By employing halide and protic additives, the catalyst poisoning effect of aliphatic amines is reversed allowing the amount nucleophile to react in high yield and ee. Second, by simply changing the halide ligand on the rhodium catalyst from chloride to iodide, the reactivity and enantioselectivity of reactions employing an aromatic amine, malonate or carboxylate nucleophile are dramatically improved. Third, through the application of halide effects and more forcing reaction conditions, less reactive oxabicycle [2.2.1] substrates react to generate synthetically useful enantioenriched cyclohexenol products. Application of these new conditions to the more reactive oxabenzonorbornadiene permits the reaction to be run with very low catalyst loadings (0.01 mol %).

Highly Efficient Rhodium-Catalyzed Asymmetric Ring-Opening Reactions of Oxabenzonorbornadiene with Amine Nucleophiles

“…1 H NMR spectra were recorded at 300 MHz using a Varian Gemini NMR spectrometer or at 400 MHz using a Varian XL 400 spectrometer with CDCl 3 as reference standard (7.24 ppm) or some other suitable solvent. Spectral features are reported in the following order: Chemical shift (d, ppm); number of protons; multiplicity (s-singlet, d-doublet, t-triplet, q-quartet, m-complex multiplet); coupling constants (J. Hz), 13 …”

“…The ee was determined to be 87% using HPLC analysis on a CHIRALCEL OD-H column, k = 254 nm. Retention times in 2% isopropanol in hexanes were 15 13 …”

“…In general, this type of reaction is highly efficient and characterized with low catalyst loading, high yield and enantioselectivities [1][2][3][4][5][6][7]. Lautens's group has extensively investigated the rhodiumcatalyzed asymmetric ring-opening reactions of oxabenzonorbornadiene with many nucleophiles including alcohols [8,9], phenols [10], amines [11] , carboxylates [12], 1,3-dicarbonyl nucleophiles [13], and sulfur nucleophiles [14] which demonstrated the great promising on providing novel and simple routes to optically active compounds [15][16][17][18]. We herein report a novel extension to Lautens's method, in which the ring of oxabenzonorbornadiene 1a was opened by aliphatic primary amines or substituted N-phenylpiperiazines secondary amines as nucleophiles in the presence of rhodium complex catalyst to afford the corresponding trans-1,2-dihydronaphth-1-ols derivatives with excellent enantioselectivities.…”

“…71.9 (c = 2.6 mg/mL, CHCl 3 ); IR (KBr, cm -1 ) 3290 (br), 2963(w), 2935(w), 2866(w), 1596(w), 1484(s), 1463(m), 1436(m), 1259(s), 1103(m), 1087(m), 1019(m), 953(m), 803(m), 714(m). 1 H NMR (400 MHz, CDCl 3 ) d 6.94(1H, d, J = 9.89 Hz), 6.81(2H, d, J = 1.09 Hz), 6.17(1H, q, J = 4.95 Hz), 5.21(1H, d, J = 2.93 Hz), 3.86(3H, s), 3.83(3H, s), 3.65(1H, t, J = 3.66 Hz), 3.15-3.19(1H, m), 2.44(1H, s(br)), 1.14(3H, d, J = 1.65 Hz), 1.13(3H, d, J = 1.65 Hz) 13. C NMR (100 MHz, CDCl 3 ) d 152.1, 149.9, 127.8, 123.7, 121.9, 121.3, 111.7, 111.1, 65.8, 56.4, 56.2, 54.9, 46.5, 23.2, 23.1; FABMS m/z, 263(M ?…”

A sub-stoichiometric tungsten-mediated Pauson–Khand reaction: Scope and limitations

“…All common reagents and solvents were obtained from commercial suppliers and used without any further purification unless otherwise indicated. FCC 1a [12] and non-commercial bicyclic olefins 2b [13], 2c [14], 2d [15], and 2e [16] were prepared following established procedures. Triethylamine was distilled over KOH.…”