Phosphinite Thioglycosides Derived from Natural d-Sugars as Useful P/S Ligands for the Synthesis of Both Enantiomers in Palladium-Catalyzed Asymmetric Substitution

Abstract

Phosphinite thioglycosides I for which a modular ­synthetic approach is reported, were found highly efficient catalyst precursors for palladium(0)-catalyzed asymmetric substitution. Both enantiomers of the allylated products have been obtained with high ee (up to 96%) using natural sugars as catalyst precursors.

P/S ligands - carbohydrates - both enantiomers - allylic substitution

References

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6

This work has been presented in part in the ISOCS-XXI, Madrid, Spain, 4-9 July 2004.

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13

Compound 12: ¹H NMR (500 MHz, CDCl₃): δ = 7.60-7.50 (m, 4 H), 7.38 -7.31 (m, 6 H), 7.21 (d, 2 H, J = 7.9 Hz), 7.02 (d, 2 H, J = 8.0 Hz), 4.58 (d, 1 H, J = 10.0 Hz), 4.35 (dd, 1 H, J = 4.5, 11.7 Hz), 4.29 (dd, 1 H, J = 7.7, 11.7 Hz), 4.23 (t, 1 H, J = 5.9 Hz), 4.13 (d, 1 H, J = 5.5 Hz), 4.02-3.93 (m, 2 H), 2.30 (s, 3 H), 1.43 (s, 3 H), 1.29 (s, 3 H), 1.19 (s, 9 H) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 178.3, 137.7, 132.4, 131.1 (d, J _PC = 11.8 Hz), 130.7 (d, J _PC = 11.8 Hz), 129.3 (d, J _PC = 26.0 Hz), 128.1 (d, J _PC = 6.8 Hz), 110.5, 88.4 (d, J _PC = 4.1 Hz), 80.4 (d, J _PC = 28.4 Hz), 79.1, 74.0, 73.7, 63.7, 38.7, 27.8, 27.1, 26.4, 21.2 ppm. ³¹P NMR (121.4 MHz, CDCl₃): δ = 119.5 ppm.
Compound 13: ¹H NMR (500 MHz, CDCl₃): δ = 7.58-7.49 (m, 4 H), 7.36-7.32 (m, 6 H), 7.23 (d, 2 H, J = 7.9 Hz), 7.03 (d, 2 H, J = 7.9 Hz), 4.56 (d, 1 H, J = 9.4 Hz), 4.33 (d, 2 H, J = 6.1 Hz), 4.23 (t, 1 H, J = 5.9 Hz), 4.13 (dd, 1 H, J = 5.5, 1.5 Hz), 4.03-3.91 (m, 2 H), 2.31 (s, 3 H), 2.07 (s, 3 H), 1.41 (s, 3 H), 1.28 (s, 3 H) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 170.8, 142.6 (d, J _PC = 18.5 Hz), 141.9 (d, J _PC = 15.4 Hz), 137.7, 132.6, 130.9 (d, J _PC = 21.8 Hz), 130.8 (d, J _PC = 21.8 Hz), 130.2, 129.3 (d, J _PC = 30.2 Hz), 128.1 (d, J _PC = 6.9 Hz), 110.6, 87.9 (d, J _PC = 4.2 Hz), 80.0 (d, J _PC = 18.4 Hz), 79.1, 73.9, 73.6, 63.8, 27.7, 26.4, 21.1, 20.8 ppm. ³¹P NMR (121.4 MHz, CDCl₃): δ = 119.4 ppm.
Compound 14: ¹H NMR (500 MHz, CDCl₃): δ = 7.57-7.50 (m, 4 H), 7.35-7.32 (m, 6 H), 5.56 (d, 1 H, J = 5.1 Hz), 4.70-4.67 (m, 1 H), 4.34-4.11 (m, 5 H), 2.02 (s, 3 H), 1.41 (s, 3 H), 1.30 (s, 12 H) ppm. ¹³C NMR (125 MHz, CDCl₃): δ = 170.7, 141.8 (d, J _PC = 19.4 Hz), 141.7 (d, J _PC = 16.0 Hz), 130.9 (d, J _PC = 21.8 Hz), 130.7 (d, J _PC = 21.7 Hz), 129.3 (d, J _PC = 2.7 Hz), 128.2 (d, J _PC = 7.0 Hz), 128.1 (d, J _PC = 7.0 Hz), 109.7, 81.3 (d, J _PC = 5.6 Hz), 77.8 (d, J _PC = 18.8 Hz), 75.6 (d, J _PC = 5.0 Hz), 73.8, 66.6, 63.5, 43.8, 31.3, 27.9, 26.3, 20.8 ppm. ³¹P NMR (121.4 MHz, CDCl₃): δ = 117.5 ppm.
Compound 15: ¹H NMR (500 MHz, CDCl₃): δ = 7.56-7.47 (m, 4 H), 7.34-7.29 (m, 6 H), 4.51 (d, 1 H, J = 9.5 Hz), 4.33-4.26 (m, 3 H), 4.15 (dd, 1 H, J = 1.8, 5.6 Hz), 3.96-3.88 (m, 2 H), 2.03 (s, 3 H), 1.42 (s, 3 H), 1.29 (s, 3 H), 1.22 (s, 9 H) ppm.¹³C NMR (125 MHz, CDCl₃): δ = 170.8, 142.9 (d, J _PC = 18.4 Hz), 142.1 (d, J _PC = 15.2 Hz), 131.3 (d, J _PC = 22.1 Hz), 130.5 (d, J _PC = 21.3 Hz), 129.0 (d, J _PC = 32.5 Hz), 128.0 (d, J _PC = 6.4 Hz), 127.9 (d, J _PC = 7.2 Hz), 110.5, 83.1 (d, J _PC = 3.3 Hz), 80.6 (d, J _PC = 18.7 Hz), 79.3 (d, J _PC = 2.7 Hz), 73.6 (2 C), 63.9, 44.1, 31.3, 27.7, 26.4, 20.8 ppm. ³¹P NMR (121.4 MHz, CDCl₃): δ = 119.8 ppm.
Compound 21: ¹H NMR (500 MHz, CDCl₃): δ = 7.54-7.46 (m, 4 H), 7.33-7.29 (m, 6 H), 4.76 (d, 1 H, J = 6.9 Hz), 4.28-4.26 (m, 1 H), 4.22 (t, 1 H, J = 5.7 Hz), 4.10-4.01 (m, 1 H), 3.70 (dd, 1 H, J = 4.4, 12.7 Hz), 1.47 (s, 3 H), 1.30 (s, 3 H), 1.19 (s, 9 H) ppm.¹³C NMR (125 MHz, CDCl₃): δ = 131.2 (d, J _PC = 22.1 Hz), 130.5 (d, J _PC = 21.4 Hz), 129.1 (d, J _PC = 31.7 Hz), 128.1 (d, J _PC = 5.9 Hz), 128.0 (d, J _PC = 6.7 Hz), 110.1, 84.5, 82.6 (d, J _PC = 4.2 Hz), 80.3 (d, J _PC = 19.2 Hz), 72.2, 63.2, 44.0, 31.3, 27.8, 26.3 ppm. ³¹P NMR (121.4 MHz, CDCl₃): δ = 118.6 ppm.

14

Typical Procedure.
To a solution of the ligand (4.3 mol%) in dry deoxygenated CH₂Cl₂ (0.5 mL), [PdCl(C₃H₅)]₂ (1.5 mol%) was added under argon. The reaction mixture was stirred for 1 h at r.t., then a catalytic amount of KOAc (0.5 mg) was added, followed by BSA (3 mol equiv) and a solution of 1,3-diphenyl-2-propenyl acetate (16, 1 mol equiv) in dry deoxygenated CH₂Cl₂ (0.7 mL). The temperature was then adjusted to the desired one (see Table [1] ) and dimethyl malonate (3 equiv) was added. Once the reaction finished as judged by TLC, the solvent was evaporated and the residue purified by column chromatography, affording the desired product 17 as a viscous oil, which solidify on standing. The ee was determined by chiral HPLC using a Chiralpack AD column (1 mL/min, i-PrOH-hexane, 5:95, 30 °C). Retention times: (R)-17: t _R = 14.2 min, (S)-17: t _R = 19.5 min.

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