dimethyl (2S)-2-methylbutanedioate

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The reaction was carried out in an Argonaut Endeavor hydrogenation vessel. The glass liner was charged with dimethyl itaconate (316 mg, 2.0 mmol) and 3,4-bis[(S,S)-2,5-diphenyl-phospholan-1-yl]-furan-2,5-dione-(1,5-cyclooctadiene) rhodium(I) tetrafluoroborate (1.7 mg, 0.002 mmol, S/C 1000). The vessel was charged to 10 bar nitrogen and vented (×5). Degassed methanol (4 ml) was added. The vessel was charged to 10 bar nitrogen and vented (×2). Stirring was commenced at 1000 rpm and the contents were heated to 25° C. The vessel was charged to 10 bar hydrogen. Hydrogen uptake was complete after 16 h. The mixture was vented and evaporated to give (S)-2-methylsuccinic acid dimethyl ester, conversion 100%, ee 96.6% (Chiraldex GTA, 30 m×0.25 mm, injector/detector 180° C., helium 14 psi, 90° C. for 6 min then ramp at 1° C./min to 105° C., retention times S 10.11 minutes, R 10.48 minutes). In comparison, much lower enantioselectivity, of 60.2% ee, is reported by Holz, J. et al, ibid., for the same transformation, at S/C 100 in methanol, catalysed by the corresponding rhodium complex of Me-Malphos [i.e. the analogue of ligand (7) with Me groups at the 2- and 5-position of each phospholane ring]. Holz, J. et al also report that a change of solvent, to THF, increases the enantioselectivity to 86% ee but this still falls short of the 96.6% ee achieved in the current example at a higher S/C ratio. The vessel was charged to 10 bar nitrogen The vessel was charged to 10 bar nitrogen evaporated

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The reaction was carried out in an Argonaut Endeavor hydrogenation vessel. The glass liner was charged with dimethyl itaconate (316 mg, 2.0 mmol) and 3,4-bis[(S,S)-2,5-diphenyl-phospholan-1-yl]-furan-2,5-dione-(1,5-cyclooctadiene) rhodium(I) tetrafluoroborate (1.7 mg, 0.002 mmol, S/C 1000). The vessel was charged to 10 bar nitrogen and vented (×5). Degassed methanol (4 ml) was added. The vessel was charged to 10 bar nitrogen and vented (×2). Stirring was commenced at 1000 rpm and the contents were heated to 25° C. The vessel was charged to 10 bar hydrogen. Hydrogen uptake was complete after 16 h. The mixture was vented and evaporated to give (S)-2-methylsuccinic acid dimethyl ester, conversion 100%, ee 96.6% (Chiraldex GTA, 30 m×0.25 mm, injector/detector 180° C., helium 14 psi, 90° C. for 6 min then ramp at 1° C./min to 105° C., retention times S 10.11 minutes, R 10.48 minutes). In comparison, much lower enantioselectivity, of 60.2% ee, is reported by Holz, J. et al, ibid., for the same transformation, at S/C 100 in methanol, catalysed by the corresponding rhodium complex of Me-Malphos [i.e. the analogue of ligand (7) with Me groups at the 2- and 5-position of each phospholane ring]. Holz, J. et al also report that a change of solvent, to THF, increases the enantioselectivity to 86% ee but this still falls short of the 96.6% ee achieved in the current example at a higher S/C ratio. The vessel was charged to 10 bar nitrogen The vessel was charged to 10 bar nitrogen evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was synthesized as described in Intermediate 11 using (S)-dimethyl 2-methylsuccinate and (S)-2-aminopropan-1-ol as starting materials. 1H NMR (CDCl3): δ 3.57 (dd, 1H), 3.32 (dd, 1H), 3.02 (br s, 1H), 2.81 (dd, 1H), 2.69 (m, 2H), 2.60 (m, 1H), 2.21 (m, 1H), 2.12 (dd, 1H), 1.98 (m, 1H), 1.32 (m, 1H), 1.04 (m, 6H); MS: 144.3 (M+H)+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was synthesized as described in Intermediate 11 using (S)-dimethyl 2-methylsuccinate and (R)-2-aminopropan-1-ol as starting materials. 1H NMR (CDCl3): δ 3.60 (dd, 1H), 3.58 (br s, 1H), 3.40 (dd, 1H), 2.89 (dd, 1H), 2.72 (m, 2H), 2.63 (m, 1H), 2.24 (m, 1H), 2.17 (dd, 1H), 2.00 (m, 1H), 1.35 (m, 1H), 1.04 (m, 6H); MS: 144.3 (M+H)+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was synthesized as described in Intermediate 11 using (S)-dimethyl 2-methylsuccinate and 2-aminoethanol as starting materials. 1H NMR (CDCl3): δ 3.66 (t, 1H), 2.93 (dd, 1H), 2.81 (m, 1H), 2.73 (m, 1H), 2.66 (m, 1H), 2.63 (m, 1H), 2.29 (m, 1H), 2.18 (dd, 2H), 2.05 (m, 1H), 1.40 (m, 1H), 1.04 (d, 3H); MS: 130.2 (M+H)+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was synthesized as described in Intermediate 11 using (S)-dimethyl 2-methylsuccinate and (S)-2-aminopropan-1-ol as starting materials. 1H NMR (CDCl3): δ 3.57 (dd, 1H), 3.32 (dd, 1H), 3.02 (br s, 1H), 2.81 (dd, 1H), 2.69 (m, 2H), 2.60 (m, 1H), 2.21 (m, 1H), 2.12 (dd, 1H), 1.98 (m, 1H), 1.32 (m, 1H), 1.04 (m, 6H); MS: 144.3 (M+H)+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was synthesized as described in Intermediate 11 using (S)-dimethyl 2-methylsuccinate and (R)-2-aminopropan-1-ol as starting materials. 1H NMR (CDCl3): δ 3.60 (dd, 1H), 3.58 (br s, 1H), 3.40 (dd, 1H), 2.89 (dd, 1H), 2.72 (m, 2H), 2.63 (m, 1H), 2.24 (m, 1H), 2.17 (dd, 1H), 2.00 (m, 1H), 1.35 (m, 1H), 1.04 (m, 6H); MS: 144.3 (M+H)+.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The title compound was synthesized as described in Intermediate 11 using (S)-dimethyl 2-methylsuccinate and 2-aminoethanol as starting materials. 1H NMR (CDCl3): δ 3.66 (t, 1H), 2.93 (dd, 1H), 2.81 (m, 1H), 2.73 (m, 1H), 2.66 (m, 1H), 2.63 (m, 1H), 2.29 (m, 1H), 2.18 (dd, 2H), 2.05 (m, 1H), 1.40 (m, 1H), 1.04 (d, 3H); MS: 130.2 (M+H)+.

Conditions: temp:25.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The reaction was carried out in an Argonaut Endeavor hydrogenation vessel. The glass liner was charged with dimethyl itaconate (316 mg, 2.0 mmol) and 3,4-bis[(S,S)-2,5-diphenyl-phospholan-1-yl]-furan-2,5-dione-(1,5-cyclooctadiene) rhodium(I) tetrafluoroborate (1.7 mg, 0.002 mmol, S/C 1000). The vessel was charged to 10 bar nitrogen and vented (×5). Degassed methanol (4 ml) was added. The vessel was charged to 10 bar nitrogen and vented (×2). Stirring was commenced at 1000 rpm and the contents were heated to 25° C. The vessel was charged to 10 bar hydrogen. Hydrogen uptake was complete after 16 h. The mixture was vented and evaporated to give (S)-2-methylsuccinic acid dimethyl ester, conversion 100%, ee 96.6% (Chiraldex GTA, 30 m×0.25 mm, injector/detector 180° C., helium 14 psi, 90° C. for 6 min then ramp at 1° C./min to 105° C., retention times S 10.11 minutes, R 10.48 minutes). In comparison, much lower enantioselectivity, of 60.2% ee, is reported by Holz, J. et al, ibid., for the same transformation, at S/C 100 in methanol, catalysed by the corresponding rhodium complex of Me-Malphos [i.e. the analogue of ligand (7) with Me groups at the 2- and 5-position of each phospholane ring]. Holz, J. et al also report that a change of solvent, to THF, increases the enantioselectivity to 86% ee but this still falls short of the 96.6% ee achieved in the current example at a higher S/C ratio. The vessel was charged to 10 bar nitrogen The vessel was charged to 10 bar nitrogen evaporated