No abstract

Treatment of the chiral oxazaborolidine 1 with AlBr3 generates the 1:1 complex 3, which is an even more potent Lewis acid catalyst than protonated 1 (i.e., 2) for enantioselective Diels−Alder reactions. Only 4 mol % of catalyst 3 is required to achieve yields and enantiomeric purities of 90% over a broad range of achiral dienes and dienophiles. The ligand from which 3 is derived can be recovered easily and with high efficiency. The method is illustrated by 22 examples.

The remarkable versatility and selectivity of the 10-(trimethylsilyl)-9-borabicyclo[3.3.2]decanes (10-TMS-9-BBDs) in the allyl- and crotylboration of representative aldehydes are reported. The new reagents are prepared through air-stable crystalline pseudoephedrine borinic ester complexes of the 10-TMS-9-BBDs (4), which are available in 63% overall yield from B-MeO-9-BBN through a simple two-step procedure. These complexes 4 are directly converted to the corresponding B-allyl-10-TMS-9-BBDs (1) with allylmagnesium bromide, which either can be isolated (98%) or used in situ for the allylations. The remarkable enantioselectivity (96 to > or =99% ee) of these reagents in the rapid (<3 h), asymmetric allylboration process at -78 degrees C is only slightly diminished when it is conducted at 25 degrees C, a phenomenon attributable to its rigid bicyclic structure. In addition to providing the homoallylic alcohols 6 efficiently (68-80%), the procedure also permits the efficient recovery of 4 (68-84%) for the direct regeneration of 1. Alternatively, an oxidative workup procedure can be used for the preparation of 6. The reagent gives predictable stereochemistry and exhibits an extremely high level of reagent control in the allylboration of d-glyceraldehyde acetonide. A simple and efficient procedure has been developed for the preparation of all four geometric and enantiomeric isomers of the B-crotyl-10-TMS-9-BBDs (10) from optically pure enantiomers of B-MeO-10-TMS-9-BBD (3). These reagents 10 also add rapidly (<3 h) and efficiently to representative aldehydes at -78 degrees C, providing ready access to all four of the possible stereoisomers of the beta-methyl homoallylic alcohols 12-15 (69-92%) in high dr (> or =98:2) and ee (94-99%).

Supporting InformationMaterials and Methods. Unless stated otherwise, reactions were performed in flame-dried glassware under a positive pressure of nitrogen using freshly distilled dry solvents. Thin-layer chromatography (TLC) was performed using E. Merck silica gel 60 F 254 precoated plates (0.25 mm). Flash chromatography was performed using Baker silica gel (40 µm particle size). NMR spectra were recorded on Varian Innova-500, or Mercury-400 instruments and calibrated using residual undeuterated solvent as an internal reference. IR spectra were recorded on Avatar 360 FT-IR spectrometer. Low-resolution and high-resolution mass spectral analyses were performed at the Harvard University Mass Spectrometry Center. Analytical high performance liquid chromatography (HPLC) was performed on Isco 2350 Series or Waters 626 HPLC using the indicated chiral column. Gas chromatography (GC) analyses were performed on Hewlett-Packard 6850 Series GC System equipped with flame ionization detector using a J & W Scientific Cyclosil-B column (30 m x 0.25 mm) or a γ-TA column (30 m x 0.25 mm). Commercial grade reagents and solvents were used without further purification except as indicated below. Dichloromethane was distilled from calcium hydride. S (S)-(-)-o-Tolyl-oxazaborolidine Precursor of 1.A 100-mL, two-necked, round-bottomed flask equipped with a stir bar, a glass stopper and a 50-mL pressure-equalizing addition funnel (containing a cotton plug and ca. 10 g of 4Å molecular sieves, 1 and functioning as a Soxhlet extractor) fitted on top with a reflux condenser and a nitrogen inlet adaptor was charged with (S)-(-)-α,α-diphenyl-2-pyrrolidinemethanol (2.59 g, 10.25 mmol, from Aldrich or Lancaster), tri-otolylboroxine 2 (1.21 g, 3.42 mmol) and 40 mL of toluene. The resulting solution was heated to reflux (bath temperature ~ 145 °C). After 3 h, the reaction mixture was cooled to ca. 60 °C and the addition funnel and condenser were quickly replaced with a short-path distillation head. The mixture was concentrated by distillation (air-cooling) to a volume of ca. 15 mL. This distillation protocol was repeated three times by re-charging with 3 x 35 mL of toluene. The solution was then allowed to cool to room temperature and the distillation head was quickly replaced with a vacuum adaptor. Concentration in vacuo (ca. 0.1 mmHg, 1 h) afforded the corresponding oxazaborolidine as clear oil. A stock solution (0.25 M) of this catalyst precursor was prepared in either toluene or dichloromethane and stored at -20 °C. A stock solution of (R)-(-)-o-Tolyloxazaborolidine (0.25 M) was prepared from (R)-(+)α,α-diphenyl-2-pyrrolidinemethanol in a similar manner. Oxazaborolidine-Aluminum Bromide Complex (S)-1.To an aliquot of the above oxazaborolidine (0.0625 mmol) in dichloromethane (0.25 mL) at -40 °C was added dropwise a solution of aluminum bromide (0.05 mmol, 0.050 mL of a 1.0 M solution in dibromomethane). A transient strong orange color developed which immediately faded to light yellow. The1 Molecular sieves (pellets) were dried in vacuo at ca....

The simple and efficient syntheses of B-allyl-10-(phenyl)-9-borabicyclo[3.3.2]decane (1) in both enantiomeric forms are reported. The remarkable enantioselectivity (81-99% ee) of these reagents in the allylboration process at -78 degrees C is only modestly diminished when the process is conducted at 0 degrees C, a phenomenon attributable to its rigid bicyclic structure. In addition to providing the homoallylic alcohols 6 efficiently (70-92%), the procedure also permits the efficient recovery of the chiral boron moiety (67-82%) as an air-stable crystalline N-methylpseudoephedrine complex 4 for the direct regeneration of 1 with allylmagnesium bromide in ether (98%). The reagent gives predictable stereochemistry, providing a strategically designed "chiral pocket" which is particularly receptive to leading methyl groups (e.g., methyl ethyl ketone, 87% ee).