ChemChat

Experimental

The following is the protocol for the synthesis of Compound 49:

A solution of fresh-prepared TFDO (1.1 eq) is added into a solution of compound 48 (7.2 mg, 0.023 mmol), which has already been dissolved in CH2Cl2 at -78 0C. The reaction mixture is then warmed up to 0 o C and stirred for 5 mins. The liquid mixture is then concentrated by vacuum filtration and the remaining residue is purified by flash chromatography to afford a separable 1:1 diastereomeric epoxides 49 and 50 (3.45 mg each, 90% yield).

Here is the reaction scheme for the synthesis of compound 49 from compound 48

The following are some cool figures about the apparatus needed for the experiment.

TFDO, also known as trifluoromethyl dioxirane, is the spotlight of this reaction. (See its even colorcoded here xD)

TFDO is an oxidizing reagent typically used to insert an oxygen atom to an unactivated C-H bond. Oxidation usually happens at the tertiary C-H bond to afford a regioselective and stereoselective oxygenated product. However, it has been found that stereoselectivity can be rendered when distant substituents on the molecule induces electron-withdrawing effect on the reactive C-H site.

A vacuum filtration, rather than a gravity filtration, is typically performed to isolate a solid (i.e. a recrystallized compound). A typical vacuum filtration apparatus is made of a filter/suction flask equipped with Buchner funnel on a rubber adapter. The side arm of the flask is hooked to a vacuum source as shown in the figure below.

Zubrick, J. The organic chem lab survival manual; John Wiley: New York, 2001.

Before running a column chromatography, TLC is usually your best friend to determine the appropriate eluent system for the column. The ideal eluent system should develop Rf value around 0.3. You can assemble the column by placing glass wool or cotton at the bottom, followed by roughly 1 cm thick layer of sand, adsorbent (silica gel), analyte, and another layer of sand. Note: Silica gel should be prepared as a slurry mixture before loading on the column because it can liberate heat when it sucks up the solvent. The slurry can be made by dissolving silica gel (25g per 1g of mixture) in the eluent solvent in a separate beaker.

Note:To develop a compacted silica layer, do not flush the solvent through the silica layer with gas.

Never leave the silica gel dry until the entire procedure is complete.