An 1,2-Elimination Approach to the Enantioselective Synthesis of 1,3-Disubstituted Linear Allenes

Abstract

The construction of 1,3-disubstituted allene skeleton, which is present in many natural allenes, via an i-PrMgBr-mediated elimination of optically active 3-acetoxy-2-iodo-prop-1-ene derviatives is exemplified through the enantioselective total synthesis of two bioactive natural allenes.

alkynes - carbanions - elimination - halides - natural products

References and Notes

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Representative Procedures
Conversion of 6a into 7
A solution of 6a (150 mg, 0.30 mmol) in dry THF (2 mL) was added dropwise via a syringe to a solution of i-PrMgBr (2 M, in Et₂O, 0.9 mL, 1.8 mmol) in dry THF (5 mL) stirred at -78 ˚C under argon. After completion of the addition, the stirring was continued at -60 ˚C for 2.5 h. Aqueous sat. NH₄Cl was added. The mixture was extracted with Et₂O (50 mL), washed with H₂O and brine before being dried over anhyd Na₂SO₄. Removal of the solvent by rotary evaporation and column chromatography (PE-EtOAc, 100:1) on silica gel gave allene 7 as a colorless oil (84 mg, 0.28 mmol, 93%) along with recovered 6a (6 mg, 0.012 mmol, 4%).
Data for 7
[α]_D ^²7 -33.7 (c 0.9, CHCl₃). ^¹H NMR (300 MHz, CDCl₃):
δ = 5.28-5.20 (m, 2 H), 4.54 (dd, J = 5.8, 2.8 Hz, 2 H), 3.62 (t, J = 6.4 Hz, 2 H), 2.07 (s, 3 H), 2.10-2.02 (m, 2 H), 1.54 (quint, J = 7.3 Hz, 2 H), 1.48 (quint, J = 7.1 Hz, 2 H), 0.90 (s, 9 H), 0.05 (s, 6 H). ^¹³C NMR (75 MHz, CDCl₃): δ = 205.4, 170.8, 92.8, 86.9, 62.90, 62.87, 32.1, 28.1, 25.9, 25.3, 21.0, 18.3, -5.3. FT-IR (film): 2955, 2930, 2858, 1963, 1744, 1227, 1103 cm^-¹. ESI-MS: m/z = 321.1 [M + Na]⁺. HRMS (MALDI): m/z calcd for C₁₆H₃₀SiO₃Na [M + Na]⁺: 321.1856; found: 321.1863.