Preparation of cis-6,6-dimethyl-3-oxa-bicyclo(3.1.0)hexan-2-one

A process for preparing an enantiomerically enriched compound of formula (VI):

• 5
• wherein X and Y are independently halogen, C1-3 alkyl or C1-3 haloalkyl;
• comprising the steps of:
• a) forming an enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone;
• b) forming a sulphonic ester of the enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone;
• and
• c) forming an enantiomerically enriched 6,6-dimethyl-3-oxabicyclo(3.1.0)hexan-2-one by reacting the sulphonic ester of the enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone with a compound of formula M(C1-6 alkoxide)y in an ether or polar solvent;
• wherein M is an alkali metal and y is 1;
• M is a quaternary ammonium cation and y is 1;
• or M is an alkaline earth metal cation and y is 2;
• d) forming an enantiomerically enriched compound of formula (VII):
• 6
• by reducing the enantiomerically enriched 6,6-dimethyl-3oxabicyclo(3.1.0)hexan-2-one;
• and
• e) ring opening the enantiomerically enriched compound of formula (VII) to produce the enantiomerically enriched compound of formula (VI).

A process for producing an enantiomerically enriched compound of formula (V):

• 7
• wherein X and Y are each independently halogen, C1-3 alkyl or C1-3 haloalkyl;
• comprising the steps of:
• a) forming an enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone;
• b) forming a sulphonic ester of the enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone;
• c) forming an enantiomerically enriched 6,6-dimethyl-3-oxabicyclo(3.1.0)hexan-2-one by reacting the sulphonic ester of the enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone with a compound of formula M(C1-6 alkoxide)y in an ether or polar solvent;
• wherein M is an alkali metal and y is 1;
• M is a quaternary ammonium cation and y is 1;
• or M is an alkaline earth metal cation and y is 2;
• d) forming an enantiomerically enriched compound of formula (VII):
• 8
• by reducing the enantiomerically enriched 6,6-dimethyl-3oxabicyclo(3.1.0)hexan-2-one;
• e) ring opening the enantiomerically enriched compound of formula (VII) to produce an enantiomerically enriched compound of formula (VI):
• 9
• wherein X and Y are as defined herein;
• and
• f) oxidizing the enantiomerically enriched compound of formula (VI) to form the enantiomerically enriched compound of formula (V).

A process for preparing cis-6,6-dimethyl-3-oxa-bicyclo(3.1.0)hexan-2-one comprising:

• a) forming an enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone;
• b) forming a sulphonic ester of the enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone;
• and
• c) reacting the sulphonic ester of the enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone with a compound of formula M(C1-6 alkoxide)y in a suitable solvent, wherein M is a suitable cation and y fulfills valency requirements.

A process for preparing an enantiomerically enriched compound of formula (VI):

• 10
• wherein X and Y are independently halogen, C1-3 alkyl or C1-3 haloalkyl;
• comprising the steps of:
• a) forming an enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone;
• b) forming a sulphonic ester of the enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone;
• and
• c) forming an enantiomerically enriched 6,6-dimethyl-3-oxabicyclo(3.1.0)hexan-2-one by reacting the sulphonic ester of the enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone with a compound of formula M(C1-6 alkoxide)y in a suitable solvent, wherein M is a suitable cation and y fulfills valency requirements;
• d) forming an enantiomerically enriched compound of formula (VII):
• 11
• by reducing the enantiomerically enriched 6,6-dimethyl-3oxabicyclo(3.1.0)hexan-2-one;
• and
• e) ring opening the enantiomerically enriched compound of formula (VII) to produce the enantiomerically enriched compound of formula (VI).

A process for producing an enantiomerically enriched compound of formula (V):

• 12
• wherein X and Y are each independently halogen, C1-3 alkyl or C1-3 haloalkyl;
• comprising the steps of:
• a) forming an enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone;
• b) forming a sulphonic ester of the enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone;
• c) forming an enantiomerically enriched 6,6-dimethyl-3-oxabicyclo(3.1.0)hexan-2-one by reacting the sulphonic ester of the enantiomerically enriched β,β-dimethyl-γ-(hydroxymethyl)-γ-butyrolactone with a compound of formula M(C1-6 alkoxide)y in a suitable solvent;
• wherein M is suitable cation and y fulfills the valency requirements;
• d) forming an enantiomerically enriched compound of formula (VII):
• 13
• by reducing the enantiomerically enriched 6,6-dimethyl-3oxabicyclo(3.1.0)hexan- 2-one;
• e) ring opening the enantiomerically enriched compound of formula (VII) to produce an enantiomerically enriched compound of formula (VI):
• 14
• wherein X and Y are as defined herein;
• and
• f) oxidizing the enantiomerically enriched compound of formula (VI) to form the enantiomerically enriched compound of formula (V).