No abstract

Unless otherwise stated, reactions were performed under a nitrogen atmosphere using freshly dried solvents. Tetrahydrofuran (THF), methylene chloride (CH 2 Cl 2), and acetonitrile (MeCN), were dried by passing through activated alumina columns. Anhydrous dimethylacetamide (DMA) was purchased from Aldrich and stored under inert atmosphere. Manganese powder (-325 mesh, 99.3%) was purchased from Alfa Aesar. Unless otherwise stated, chemicals and reagents were used as received. All reactions were monitored by thin-layer chromatography using EMD/Merck silica gel 60 F254 pre-coated plates (0.25 mm) and were visualized by UV, panisaldehyde, or KMnO 4 staining. Flash column chromatography was performed as described by Still et al. 1 using silica gel (partical size 0.032-0.063) purchased from Silicycle. Optical rotations were measured on a Jasco P-2000 polarimeter using a 100 mm path-length cell at 589 nm. 1 H and 13 C NMR spectra were recorded on a Varian 400 MR (at 400 MHz and 101 MHz, respectively) or a Varian Inova 500 (at 500 MHz and 126 MHz, respectively), and are reported relative to internal CHCl 3 (1 H, ! = 7.26) or acetone (1 H, ! = 2.05), and CDCl 3 (13 C, ! = 77.0) or acetone (13 C, ! = 29.8). Data for 1 H NMR spectra are reported as follows: chemical shift (! ppm) (multiplicity, coupling constant (Hz), integration). Multiplicity and qualifier abbreviations are as follows: s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet, br = broad, app = apparent. IR spectra were recorded on a Perkin Elmer Paragon 1000 spectrometer and are reported in frequency of absorption (cm-1). HRMS were acquired using an Agilent 6200 Series TOF with an Agilent G1978A Multimode source in electrospray ionization (ESI) or mixed (MM) ionization mode, or obtained from the Caltech Mass Spectral Facility in fast-atom bombardment mode (FAB). Analytical SFC was performed with a Mettler SFC supercritical CO 2 analytical chromatography system with Chiralcel AD-H, OD-H, ASH , OB-H, and OJ-H columns (4.6 mm x 25 cm) with visualization at 210 nm. Analytical achiral GC was performed with an Agilent 6850 GC utilizing an Agilent DB-WAX (30.0 m x 0.25 mm) column (1.0 mL/min He carrier gas flow).

An asymmetric Ni-catalyzed reductive cross-coupling of (hetero)aryl iodides and benzylic chlorides has been developed to prepare enantioenriched 1,1-diarylalkanes. As part of these studies, a new chiral bioxazoline ligand, 4-heptyl-BiOX (L1), was developed in order to obtain products in synthetically useful yield and enantioselectivity. The reaction tolerates a variety of heterocyclic coupling partners, including pyridines, pyrimidines, indoles, and piperidines.

A Ni-catalyzed asymmetric reductive cross-coupling of heteroaryl iodides and α-chloronitriles has been developed. This method furnishes enantioenriched α,α-disubstituted nitriles from simple organohalide building blocks. The reaction tolerates a variety of heterocyclic coupling partners, including pyridines, pyrimidines, quinolines, thiophenes, and piperidines. The reaction proceeds under mild conditions at room temperature, and precludes the need to pre-generate organometallic nucleophiles.

The first examples of iminium catalyzed Nazarov cyclizations of divinyl ketones are presented. Experiments describing hydroxylamine catalysis of the cyclization of eight alkoxy divinyl ketones (60-79% yield) and one unactivated divinyl ketone (38% yield) are reported. Phenyl substitution at the -position of the divinyl ketone inhibits cyclization, whereas alkyl substituted -alkoxy divinyl ketones readily cyclize.