(6R,10R)-6,10,14-trimetylpentadecan-2-one prepared from 6,10-dimetylundec-5-en-2-one or 6,10-dimetylundeca-5,9-dien-2-one
AssigneeDsm IP Assets B.V.
InventorsWerner Bonrath, Thomas Netscher, Jonathan Alan Medlock, René Tobias Stemmler, Johannes Tschumi, Gerardus Karel Maria Verzijl, Andreas Hendrikus Maria De Vries
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Abstract
The present invention relates to a process of manufacturing (6R,10R)-6,10,14-trimetylpentadecan-2-one in a multistep synthesis from 6,10-dimetylundec-5-en-2-one or 6,10-dimetylundeca-5,9-dien-2-one. The process is very advantageous in that it forms in an efficient way the desired chiral product from a mixture of stereoisomers of the starting product.
Claims17
A process of manufacturing (6R,10R)-6,10,14-trimethylpentadecan-2-one in a multistep synthesis from 6,10-dimethylundec-5-en-2-one or 6,10-dimethylundeca-5,9-dien-2-one comprising the sequential steps of:
- a) providing a mixture of (E)-6,10-dimethylundec-5-en-2-one and (Z)-6,10-dimethylundec-5-en-2-one or a mixture of (E)-6,10-dimethylundeca-5,9-dien-2-one and (Z)-6,10-dimethylundeca-5,9-dien-2-one;
- b) separating one isomer of 6,10-dimethylundec-5-en-2-one or of 6,10-dimethylundeca-5,9-dien-2-one from the mixture of step a);
- c) conducting asymmetric hydrogenation using molecular hydrogen in the presence of a chiral iridium complex and yielding (R)-6,10-dimethylundecan-2-one;
- d) chemically transforming (R)-6,10-dimethylundecan-2-one to a mixture of (R,E)-6,10,14-trimethylpentadec-5-en-2-one and (R,Z)-6,10,14-trimethylpentadec-5-en-2-one;
- e) separating one isomer of (R)-6,10,14-trimethylpentadec-5-en-2-one from the mixture obtained in step d);
- and
- f) conducting asymmetric hydrogenation using molecular hydrogen in the presence of a chiral iridium complex and yielding (6R,10R)-6,10,14-trimethylpentadecan-2-one, wherein
- step d) is practiced by:
- d1) ethynylation of (R)-6,10-dimethylundecan-2-one using ethyne in the presence of a basic substance to yield (7R)-3,7,11-trimethyldodec-1-yn-3-ol;
- and
- d2) hydrogenation of (7R)-3,7,11-trimethyldodec-1-yn-3-ol with molecular hydrogen in the presence of a Lindlar catalyst to yield (7R)-3,7,11-trimethyldodec-1-en-3-ol;
- or step d) is practiced by:
- d1′) vinylation of (R)-6,10-dimethylundecan-2-one by addition of a vinyl Grignard reagent to yield (7R)-3,7,11-trimethyldodec-1-en-3-ol;
- followed by either
- d3) reacting (7R)-3,7,11-trimethyldodec-1-en-3-ol with 2-methoxyprop-1-ene to yield a mixture of (R,E)-6,10,14-trimethylpentadec-5-en-2-one and (R,Z)-6,10,14-trimethylpentadec-5-en-2-one;
- or
- d3′) reacting (7R)-3,7,11-trimethyldodec-1-en-3-ol with an alkyl acetoacetate or diketene in the presence of a base and/or an acid to yield a mixture of (R,E)-6,10,14-trimethylpentadec-5-en-2-one and (R,Z)-6,10,14-trimethylpentadec-5-en-2-one.
A process of manufacturing compound of formula (V) comprising manufacturing (6R,10R)-6,10,14-trimethylpentadecan-2-one according to 1, followed by the steps of:
- g) ethynylation of (6R,10R)-6,10,14-trimethylpentadecan-2-one using ethyne in the presence of a basic substance to yield (7R,11R)-3,7,11,15-tetramethylhexadec-1-yn-3-ol;
- and either
- h) hydrogenation of (7R,11R)-3,7,11,15-tetramethylhexadec-1-yn-3-ol with molecular hydrogen in the presence of a Lindlar catalyst to yield (R,R)-isophytol;
- or
- h′) vinylation of (6R,10R)-6,10,14-trimethylpentadecan-2-one by addition of a vinyl Grignard reagent to yield (R,R)-isophytol;
- and then subsequently followed by the step of:
- m) condensing (R,R)-isophytol with a compound of formula (VI) to yield the compound of formula (V) being an isomeric mixture in view of the chirality at the centre indicated by the symbol #;
- and wherein the symbol # represents a stereogenic centre.
A composition comprising:
- at least one ketal of formula (XI) or (XII);
- and
- at least one chiral iridium complex,
- wherein a wavy line represents a carbon-carbon bond which is linked to the adjacent carbon-carbon double bond so as to have the carbon-carbon double bond either in the Z or in the E-configuration;
- and wherein
- the double bond having dotted lines in formula (XI) represent either a single carbon-carbon bond or a double carbon-carbon bond;
- and wherein
- the symbol represents a stereogenic centre;
- and wherein
- Q1 and Q2 stand either individually or both for a C1-C10 alkyl group or a halogenated C1-C10 alkyl group;
- or Q1 and Q2 form together a C2-C6 alkylene group or a C6-C8 cycloalkylene group.
A ketal of formula (XX-A), (XX-B), (XX-C) or (XX-D):
- wherein the double bond having dotted lines () in the above formulae represents either a single carbon-carbon bond or a double carbon-carbon bond;
- and wherein
- a wavy line represents a carbon-carbon bond which is linked to an adjacent single carbon bond ( representing—) or to an adjacent carbon-carbon double bond ( representing═) so as to have the carbon-carbon double bond either in the Z or in the E-configuration.
Dependencies are inferred from the claim text.