Diiodomethane → HCID 118353312, compound

Participants

Reaction Conditions

Reaction Steps

Following a published procedure for asymmetric allylic cyclopropanation: To dimethoxyethane (DME) (1.39 g, 1.60 mL, 15.4 mmol, 1.90 equiv) in CH2Cl2 (50 mL) in a flame-dried round-bottom flask under a N2 atmosphere cooled in an ethyleneglycol/CO2 bath at −15 ° C. was added diethylzinc (2.01 g, 1.67 mL, 16.3 mmol, 2.00 equiv), while maintaining the bath temperature between −15 and −10 ° C. CH2I2 (8.70 g, 2.62 mL, 32.5 mmol, 4.00 equiv) was added dropwise over 20 minutes at −15 ° C. The reaction mixture was stirred at −15 ° C. for 10 minutes. A solution of (4R,5R)-2-butyl-N,N,N′,N′-tetramethyl-1,3,2-dioxaborolane-4,5-dicarboxamide (2.63 g, 2.46 mL, 9.75 mmol, 1.20 equiv) in CH2Cl2 (10 mL) from a separate flame-dried round-bottom flask under a N2 atmosphere was added over 5 minutes via syringe. A solution of (E)-3-(5-bromo-2-(cyclopropylmethoxy)phenyl)prop-2-en-1-ol (S7) (2.30 g, 8.12 mmol, 1.00 equiv) in CH2Cl2 (10 mL) from a separate flame-dried round-bottom flask under a N2 atmosphere was added over 5 minutes via syringe. The reaction mixture was allowed to warm to 23 ° C. and stirred for 20 hours. Saturated aqueous NH4Cl solution (10 mL) and 1M HC1 (50 mL) were added to the reaction mixture. The reaction mixture was transferred to a separatory funnel. Diethyl ether (200 mL) was added and the separatory funnel was shaken and the organic phase was separated. The aqueous phase was extracted from with diethyl ether (200 mL) and then again with diethyl ether (100 mL). The combined organic phases were transferred to an Erlenmeyer flask. 2 M NaOH solution (60 mL) and 30% H2O2 solution (15 mL) were added. The reaction mixture was stirred vigorously for 5 minutes. The reaction mixture was transferred into a separatory funnel and partitioned. The organic phase was washed with 1.0 M aqueous HC1 (75 mL), saturated aqueous Na2CO3 solution (75 mL), saturated aqueous NaHCO3 solution (75 mL) and brine (75 mL). The organic phase was dried with MgSO4, and concentrated in vacuo. The residue was purified by chromatography on silica gel, eluting with a gradient of 10-30% EtOAc in hexanes (v/v) to afford 2.21 g of the title compound as a colorless oil (92% yield and 96% ee as determined on a Chiracel ODH column with 5% isopropanol/hexanes eluent (see FIG. 2A). Racemic S8 was synthesized using the above procedures omitting the addition of (4R,5R)-2-butyl-N,N,N′,N′-tetramethyl-1,3,2-dioxaborolane-4,5-dicarboxamide. Absolute stereochemistry was assigned by analogy.

Provenance & Evidence