An efficient stereoselective synthesis of a racemic CD-intermediate of vitamin D

A highly efficient four-step approach to the racemic CD-intermediate 8 from the racemic hydrindenone 10 has been developed. In the key step, the hydrindenone 10 is converted stereoselectively into the (±)-bromohydrindenone 17. Oxygen transposition from C-9 to C-8 is effected by means of conversion of 17 to the epoxide 20 and regioselective reductive ring opening of 20 with DIBALH. The resulting (±)-hydrindanol 8 was converted by the Horner-Wittig reaction with α-methacrolein into the diene 24, hydrogenation of which provided the racemic hydrindanol 25. This is a direct precursor of racemic Grundmann's ketone 9 and bears the alkyl side chain and the correct relative configuration at C13, C14, C17, and C20 of Vitamin D

Investigations into the reaction of the lithium enolate of cyclohexanone and phenyl vinyl sulfoxide: A simple synthesis of a bicyclo[4.2.0]octan-1-ol

The enolate generated from cyclohexanone and LDA at -78° C in THF reacts with (±)-phenyl vinyl sulfoxide to give the novel sulfinylbicyclo[4.2.0]octanols 1-3 and monoalkylated sulfoxide 4. The effects of changes in temperature, concentration, and reaction time were studied. By accurate control of temperature, concentration, and reaction time the ratio of bicyclooctanols 1-3 to monoalkylated sulfoxide 4 obtained was 95 : 5. The bicyclooctanols 1-3 were characterised as the sulfones 5 and 6. The relative stereochemistries of the bicyclooctanols 1-3 were established by X-ray structural determination

Probing the formation of Bicyclo[4.2.0]octan-1-ols

Reaction of lithium enolates of simple ketones with (±)-phenyl vinyl sulfoxide has potential for the convergent construction of complex fused ring systems containing a bicyclo[n.2.0]alkan-1-ol. The formation of sulfinylbicyclo[4.2.0]octan-1-ols 1−3 from the lithium enolate of cyclohexanone with (±)-phenyl vinyl sulfoxide or (R)-(+)-p-tolyl vinyl sulfoxide 18 was used to probe the mode of this novel cyclization reaction. Using phenyl vinyl sulfoxide, variations in the reaction lighting and solvent were investigated, in conjunction with radical trapping (TEMPO) and isotope labeling (deuterium) experiments. Cyclization to form sulfinylbicyclooctanols 1−3 is likely to proceed via an intermediate that ring closes to the bicycloalkanol anion 11 and was presently favored by the use of solvents such as THF or DME

Some stability and stereochemical considerations of simple Bicyclo[4.2.0]octanols

Bicyclooctanols 3 and 4 were formed with control of the stereochemistry at C8 by using an aluminium enolate of cyclohexanone in 1,2-dimethoxyethane. Bicyclooctanols 1 and 3 were stable towards aqueous hydrochloric acid for short times (< 3.5 h), and ring open to a diastereomeric mix of monoalkylated 5 under protic or aprotic conditions in the presence of base (NaOH or lithium diisopropylamide). The rate of ring opening appears to be dependent on reaction temperature. Bicyclooctanols 1, 3, and 4 displayed remarkable stability when heated at reflux in benzene, whereas use of ethanol prompted stereoselective ring opening of 1 and 3 to give individual diastereomers of monoalkylated 5 and ring opening of 4 to give a 50 : 50 mix of diastereomers of 5. This unexpected result was attributed to the stereochemistry of the bicyclooctanol and placement of hydrogen-bonding sites