Search

US-12617763-B2 - Hydroboration-oxidation process

US12617763B2US 12617763 B2US12617763 B2US 12617763B2US-12617763-B2

Abstract

The present invention relates to the field of organic synthesis and, more specifically, it concerns a process for preparing compound of formula (I) by a hydroboration-oxidation reaction of compound of formula (II).

Inventors

  • Francesco Santoro

Assignees

  • FIRMENICH SA

Dates

Publication Date
20260505
Application Date
20210302
Priority Date
20200305

Claims (19)

  1. 1 . A process for the preparation of a compound of formula (I) in the form of any one of its stereoisomers or a mixture thereof, said process comprising the hydroboration—oxidation of a compound of formula (II) in the form of any one of its stereoisomers or a mixture thereof, wherein the hydroboration is carried out in the presence of MBH 4 and a carboxylic acid wherein M represents an alkaline metal.
  2. 2 . The process according to claim 1 , wherein MBH 4 is selected from the group consisting of NaBH 4 , LiBH 4 and KBH 4 .
  3. 3 . The process according to claim 1 , wherein the carboxylic acid is of formula R(COOH) n wherein n is 1 or 2, R is a hydrogen atom or a C 1-10 hydrocarbon optionally substituted by one to five C 1-3 alkoxy groups, hydroxy groups or halogen atoms.
  4. 4 . The process according to claim 1 , wherein R is a C 1-5 alkyl group or a phenyl group and n is 1.
  5. 5 . The process according to claim 1 , wherein the carboxylic acid is acetic acid, propionic acid, butyric acid, valeric acid, isovaleric acid, benzoic acid, trifluoroacetic acid, malonic acid, tartaric acid, lactic acid or a mixture thereof.
  6. 6 . The process according to claim 1 , wherein the ratio between MBH 4 and the carboxylic acid is 1:1 to 1:2.
  7. 7 . The process according to claim 1 , wherein the oxidation is carried out in the presence of hydrogen peroxide, sodium perborate, potassium perborate, sodium percarbonate, potassium percarbonate, peracetic acid, sodium peroxomonosulfate, sodium peroxodisulfate, potassium peroxomonosulfate, potassium peroxodisulfate, sodium hypochlorite or dioxygen.
  8. 8 . The process according to claim 1 , wherein compound of formula (I) is (1R,2S,5R)-2-(1-hydroxypropan-2-yl)-5-methylcyclohexan-1-ol.
  9. 9 . The process according to claim 1 , wherein compound of formula (II) is (1R,2S,5R)-5-methyl-2-(prop-1-en-2-yl)cyclohexan-1-ol.
  10. 10 . The process according to claim 1 , wherein the oxidation is performed in a presence of base.
  11. 11 . A process for preparing a compound of formula (III) in the form of any one of its stereoisomers or a mixture thereof, said process comprising i) a hydroboration—oxidation of a compound of formulae (II) into a compound of formula (I) as defined in claim 1 ; and ii) a dehydrogenation/cyclisation of the compound of formula (I) into compound of formula (III).
  12. 12 . The process according to claim 2 , wherein the carboxylic acid is acetic acid, propionic acid, butyric acid, valeric acid, isovaleric acid, benzoic acid, trifluoroacetic acid, malonic acid, tartaric acid, lactic acid or a mixture thereof.
  13. 13 . The process according to claim 12 , wherein the ratio between MBH 4 and the carboxylic acid is 1:1 to 1:2.
  14. 14 . The process according to claim 12 , wherein the carboxylic acid is of formula R(COOH) n wherein n is 1 or 2, R is a hydrogen atom or a C 1-10 hydrocarbon optionally substituted by one to five C 1-3 alkoxy groups, hydroxy groups or halogen atoms.
  15. 15 . The process according to claim 14 , wherein R is a C 1-5 alkyl group or a phenyl group and n is 1.
  16. 16 . The process according to claim 12 , wherein the oxidation is performed in a presence of base.
  17. 17 . The process according to claim 12 , wherein the oxidation is carried out in the presence of hydrogen peroxide, sodium perborate, potassium perborate, sodium percarbonate, potassium percarbonate, peracetic acid, sodium peroxomonosulfate, sodium peroxodisulfate, potassium peroxomonosulfate, potassium peroxodisulfate, sodium hypochlorite or dioxygen.
  18. 18 . The process according to claim 15 , wherein the oxidation is performed in a presence of base.
  19. 19 . The process according to claim 15 , wherein the oxidation is carried out in the presence of hydrogen peroxide, sodium perborate, potassium perborate, sodium percarbonate, potassium percarbonate, peracetic acid, sodium peroxomonosulfate, sodium peroxodisulfate, potassium peroxomonosulfate, potassium peroxodisulfate, sodium hypochlorite or dioxygen.

Description

This present application is a U.S. national phase entry under 35 U.S.C. § 371 of PCT Application No. PCT/EP2021/055205, filed Mar. 2, 2021, which claims priority to European Patent Application No. 20161240.5, filed Mar. 5, 2020. The entire contents of these applications are explicitly incorporated herein by this reference. TECHNICAL FIELD The present invention relates to the field of organic synthesis and, more specifically, it concerns a process for preparing compound of formula (I) by a hydroboration-oxidation reaction of compound of formula (II). BACKGROUND OF THE INVENTION 3,6-dimethylhexahydro-1-benzofuran-2(3H)-one is highly valuable perfumery ingredient also known as Koumalactone® or Natactone® (origin: Firmenich SA). Said compounds may be obtained through the hydroboration-oxidation of 5-methyl-2-(prop-1-en-2-yl)cyclohexan-1-ol followed by oxidation with KMnO4. Nevertheless, typical conditions used for the hydroboration such as NaBH4 and BF3-Et2O generate in the meantime diborane, a highly toxic and explosive compound. So, there is a need to develop a new approach toward 3,6-dimethylhexahydro-1-benzofuran-2(3H)-one using reagents which may be safer and more easily used at a larger scale while maintaining even increasing the general yield and avoiding the formation of side products. The present invention allows obtaining compound of formula (I) with high selectivity starting from compound of formula (II) under hydroboration-oxidation conditions wherein the hydroboration is performed in the presence of MBH4 and a carboxylic acid wherein M represents an alkaline metal. SUMMARY OF THE INVENTION The invention relates to the hydroboration-oxidation of compound of formula (II) without the formation of toxic and explosive borane allowing the preparation of compound of formula (I) in high yield and in a safer way. So, the first object of the present invention is process for the preparation of a compound of formula (I) in the form of any one of its stereoisomers or a mixture thereof; comprising the hydroboration—oxidation of compound of the formulae (II) in the form of any one of its stereoisomers or a mixture thereof; wherein the hydroboration is carried out in the presence of MBH4 and a carboxylic acid wherein M represents an alkaline metal. A second object of the present invention is a process for preparing a compound of formula (III) in the form of any one of its stereoisomers or a mixture thereof Comprising the Steps of i) a hydroboration—oxidation of compound of the formulae (II) into compound of formula (I) as defined in claims 1 to 10ii) a dehydrogenation/cyclisation of compound of formula (I) into compound of formula (III). DESCRIPTION OF THE INVENTION It has now been surprisingly found that the hydroboration of compound of formula (II) may be carried out with MBH4 and a carboxylic acid avoiding the formation of borane. Said conditions allow preparing compound of formula (I) by hydroboration-oxidation conditions while being safe and with a high selectivity toward the Anti-Markovnikov product. So, the first object of the invention is a process for the preparation of a compound of formula (I) in the form of any one of its stereoisomers or a mixture thereof; comprising the hydroboration—oxidation of compound of the formulae (II) in the form of any one of its stereoisomers or a mixture thereof; wherein the hydroboration is carried out in the presence of MBH4 and a carboxylic acid wherein M represents an alkaline metal. For the sake of clarity, by the expression “any one of its stereoisomers or a mixture thereof”, or the similar, it is meant the normal meaning understood by a person skilled in the art, i.e. that the compounds of formula (I) and (II) can be a pure enantiomer or diastereomer. In other words, the compounds of formula (I) and (II) possess several stereocenters and each of said stereocenter can have two different stereochemistries (e.g. R or S). The compounds of formula (I) and (II) may even be in the form of a pure enantiomer or in the form of a mixture of enantiomers or diastereoisomers. The compounds of formula (I) and (II) can be in a racemic form or scalemic form. Therefore, the compounds of formula (I) and (II) can be one stereoisomer or in the form of a composition of matter comprising, or consisting of, various stereoisomers. According to a particular embodiment, compound of formula (II) is in a racemic form providing a compound of formula (I) in a racemic form. For example, the compound of formula (II) may be (1RS,2SR,5RS)-5-methyl-2-(prop-1-en-2-yl)cyclohexan-1-ol providing compound of formula (I) being (1RS,2SR,5RS)-2-(1-hydroxypropan-2-yl)-5-methylcyclohexan-1-ol; i.e. compound of formula (I) is in the form of a composition of matter comprising, even consisting of, (1RS,2SR,5RS)-2-((S)-1-hydroxypropan-2-yl)-5-methylcyclohexan-1-ol and (1RS,2SR,5RS)-2-((R)-1-hydroxypropan-2-yl)-5-methylcyclohexan-1-ol. According to another particular embodiment, compound of formula (II) may be i