Compound 2k

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Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.

Prepared according to general procedure 2 outlined for compound 2a from methyl 2,2-di(but-3-en-1-yl)-6-methyl-3-oxohept-5-enoate 1k (37.3 mg, 0.134 mmol). 1,4-Cyclohexadiene (152 µL, 1.61 mmol) was added prior to substrate addition. After a reaction time of 26 h at −50 °C, the crude product was purified by column chromatography (hexane/EtOAc 98:2 to 96:4 to elute the product, then 80:20 to elute ligand 3f) to afford 2k as a colorless oil (27.4 mg, 73%, dr: 92:8, er: 98:2). A small amount of product was purified again by column chromatography (hexane/EtOAc 98:2 to 96:4) to afford the pure major diastereomer for analysis.

Major diastereomer (1 S ,3a R ,5 S ,6a R): ¹H NMR (400 MHz, CDCl₃) δ 5.78 (ddt, 1 H, J = 17.1, 10.3, 6.4 Hz, CH=CH₂), 5.00 (d, 1 H, J = 17.1 Hz, CH=CH_{c i s}H_trans), 4.93 (d, 1 H, J = 10.3 Hz, CH=CH_cisH_{t r a n s}), 4.03 (d, 1 H, J = 2.0 Hz, OH), 3.72 (s, 3 H, CO₂CH₃), 2.35–2.23 (m, 3 H, iPrCHCH₂CH + iPrCHCH_aH_bCH + CH₂CH_aH_bCH=CH₂), 2.05–1.78 (m, 6 H, CH_aH_bCCO₂CH₃ + CH₂CH_aH_bCH=CH₂ + iPrCH + CH_aH_bCH₂CCO₂CH₃ + CH_aH_bCH₂CH=CH₂ + CH_aH_bCOH), 1.73–1.63 (m, 2 H, CH_aH_bCH₂CH=CH₂ + CH_aH_bCCO₂CH₃), 1.36 (dqq, 1 H, J = 8.1, 6.6, 6.6 Hz, (CH₃)₂CH), 1.20 (td, 1 H, J = 12.2, 2.3 Hz, CH_aH_bCOH), 1.16–1.08 (m, 1 H, CH_aH_bCH₂CCO₂CH₃), 0.92 (d, 3 H, J = 6.6 Hz, (CH₃)_a(CH₃)_bCH), 0.90 (d, 3 H, J = 6.6 Hz, (CH₃)_a(CH₃)_bCH), 0.84–0.76 (m, 1 H, iPrCHCH_aH_bCH); ¹³C NMR (100 MHz, CDCl₃) δ 178.2 (CO₂CH₃), 138.6 (CH=CH₂), 114.4 (CH=CH₂), 93.1 (COH), 58.1 (CCO₂CH₃), 51.9 (CO₂CH₃), 50.9 (CHCOH), 46.9 (iPrCH), 41.6 (CH₂COH), 40.3 (iPrCHCH₂CH), 35.0 (CH₂CH₂CCO₂CH₃), 33.6 ((CH₃)_a(CH₃)_bCH), 33.2 (CH₂CH₂CH=CH₂), 30.0 (CH₂CH₂CH=CH₂), 29.8 (CH₂CH₂CCO₂CH₃), 21.9 ((CH₃)_a(CH₃)_bCH), 21.5 ((CH₃)_a(CH₃)_bCH); IR v_max (neat/cm^-1): 506, 2950, 2870, 1706, 1640, 1457, 1433, 1383, 1365, 1276, 1244, 1203, 1152, 1035, 991, 909, 859, 816, 774, 739, 635; HRMS (APCI) calcd for C₁₇H₂₉O₃, [M+H]⁺: 281.2111, found 281.2104. [α]²²_D = +50.1 (c = 0.26, CH₂Cl₂).

Minor diastereomer (1 S ,3a R ,5 R ,6a R), diagnostic visible signals only: ¹H NMR (400 MHz, CDCl₃) δ 3.87 (s, 1 H, OH), 3.69 (s, 3 H, CO₂CH₃); ¹³C NMR (100 MHz, CDCl₃) δ 177.9 (CO₂CH₃), 138.5 (CH=CH₂), 114.5 (CH=CH₂), 93.0 (COH), 52.0 (CO₂CH₃), 41.3 (CH₂COH), 40.4 (iPrCHCH₂CH).

Enantiomeric purity of the product (major diastereomer) was determined by GC analysis (ChiraSil^® DEX CB 25m x 0.25mm column, isothermal at 100 °C (480 min)/100 °C to 160 °C (0.5 °C/min), flow rate = 1.0 mL/min, retention time: 522.8 min (major), 545.5 min (minor); er: 98:2.