Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
  • C07C49/657—Unsaturated compounds containing a keto groups being part of a ring containing six-membered aromatic rings
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
  • C07C45/51—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition
  • C07C45/516—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by pyrolysis, rearrangement or decomposition involving transformation of nitrogen-containing compounds to >C = O groups
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C45/00—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds
  • C07C45/61—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups
  • C07C45/65—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups
  • C07C45/66—Preparation of compounds having >C = O groups bound only to carbon or hydrogen atoms; Preparation of chelates of such compounds by reactions not involving the formation of >C = O groups by splitting-off hydrogen atoms or functional groups; by hydrogenolysis of functional groups by dehydration
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/385—Saturated compounds containing a keto group being part of a ring
  • C07C49/403—Saturated compounds containing a keto group being part of a ring of a six-membered ring
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
  • C07C49/593—Unsaturated compounds containing a keto groups being part of a ring of a three- or four-membered ring
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
  • C07C49/597—Unsaturated compounds containing a keto groups being part of a ring of a five-membered ring
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
  • C07C49/613—Unsaturated compounds containing a keto groups being part of a ring polycyclic
  • C07C49/617—Unsaturated compounds containing a keto groups being part of a ring polycyclic a keto group being part of a condensed ring system
  • C07C49/623—Unsaturated compounds containing a keto groups being part of a ring polycyclic a keto group being part of a condensed ring system having two rings
  • C07C49/633—Unsaturated compounds containing a keto groups being part of a ring polycyclic a keto group being part of a condensed ring system having two rings the condensed ring system containing eight or nine carbon atoms
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
  • C07C49/00—Ketones; Ketenes; Dimeric ketenes; Ketonic chelates
  • C07C49/587—Unsaturated compounds containing a keto groups being part of a ring
  • C07C49/613—Unsaturated compounds containing a keto groups being part of a ring polycyclic
  • C07C49/617—Unsaturated compounds containing a keto groups being part of a ring polycyclic a keto group being part of a condensed ring system
  • C07C49/623—Unsaturated compounds containing a keto groups being part of a ring polycyclic a keto group being part of a condensed ring system having two rings
  • C07C49/637—Unsaturated compounds containing a keto groups being part of a ring polycyclic a keto group being part of a condensed ring system having two rings the condensed ring system containing ten carbon atoms

Definitions

• the present invention relates to synthetic compounds having a chiral quaternary carbon atom, a general method of synthesis by asymmetric induction of these compounds as well as their application in obtaining organic products, in particular natural products.
• Another object of the present invention is therefore a general method of synthesis which makes it possible to avoid recourse to methods of resolution by resolution of the racemates and to directly obtain products of satisfactory optical purity.
• the present invention relates to the elective preparation of one or the other of the two enantiomers of a synthetic imine compound containing in particular a quaternary chiral carbon atom and a functionalized group located respectively in ⁇ and in ⁇ of the imine function, as well as a chiral carbon atom linked to the nitrogen of this imine function and having the formula
• R 1 represents one of the following functionalized groups: CN, NO 2 , COR 9 , COOR 10 , CONR 10 R 11 , SO 2 R 12 ;
• R 2 is H or has the same meaning as R 1 ;
• - R 3 is H, an alkyl containing from 1 to 3 carbon atoms, or the group OR 12 ; - R 4 and R 5 represent an alkyl containing from 1 to 10 carbon atoms, an aryl or one of the groups: COOR 12 , CH 2 COOR 12 , OR 12 , CH 2 OR 12 , (CH 2 ) 2 OR 10 , (CH 2 ) 3 OR 10 , COR 10 , C (R ' 3 ) 2 CHR' 1 R ' 2 ; R ' 1 , R' 2 and R ' 3 being chosen from the same substituents respectively as R 1 , R 2 and R 3 , but at least one being different from its counterpart, and R 4 and R 5 are different, and
• R 6 is H, aryl, COOR 12 , an saturated or unsaturated alkyl and containing from 1 to 8 carbon atoms or
• R 4 and R 6 form a ring comprising from 4 to 8 carbon atoms, which can include a carbonyl group located at ⁇ of the chiral carbon or which can be condensed to an aromatic ring at ⁇ , ⁇ of the imine group, and for the rings with 6, 7 or 8 carbon atoms, which may include a carbonyl group located at p of the chiral carbon or, which may be condensed to an aromatic ring at ⁇ , ⁇ of the chiral carbon;
• R 7 represents an aryl, a branched alkyl containing from 3 to 6 carbon atoms, a cycloalkyl containing 5 or 6 carbon atoms or the group COOR 12 ;
• R 8 represents a linear alkyl containing from 1 to 3 carbon atoms
• R 9 represents H, an alkyl containing from 1 to 7 carbon atoms, (CH 2 ) 3 COOR 10 , an aryl or a halogen;
• R 10 and R 11 represent H, an alkyl containing from 1 to 6 carbon atoms or an aryl, may be equal or different or be linked to form a heterocycle of 5 or 6 atoms;
• R 4 , R 5 , R 6 , R 7 and R 8 have the meanings indicated above.
• one of the two diasterequals / imine of possible reoisomers of formula (1) is predominantly obtained (> 95%) despite the fact that the imine of formula (3) is a mixture containing appreciable amounts its two chiral diastereoisomers.
• the compounds according to the present invention have a structure according to formula (1) in which:
• R 1 , R 2 , R 5 , R 7 , R 9 , R 10 , R 11 , R 12 , R ' 1 , R' 2 and R ' 3 have the meaning indicated above;
• R 3 is H or CH 3 ;
• R 4 and R 6 form a ring with 4, 5 or 6 carbon atoms of structure
• n and m are 0 or 1
• R 13 , R 14 and R 15 are H, an alkyl containing from 1 to 3 carbon atoms or OR 12 , the OR 12 groups possibly forming a ring of 5 to 7 atoms
• R 16 is H or has the same meaning as R 5 , and
• R 8 is CH 3 .
• R 1 , R 7 , R 16 and n have the meanings indicated above, and
• the first example concerns the chiral imine of formula
• A represents the group -O-CH 2 -CH 2 -O- or represents a doubly bound oxygen atom
• A represents the group -O-CH 2 -CH 2 -O- the product resulting from the selective hydrolysis of the imine function is cyclized between the carbon atom located at ⁇ of the ketone group of the side chain and the ketonic grouping of the cycle to give a key intermediate in the synthesis of interesting steroids.
• A represents an oxo group, the compound is cyclized directly, in an analogous manner.
• octahydroindolic alkaloids such as those of the families Amaryllis, Sceletium, Aspidosperma and Strychnos, some of which are anti-tumor.
• the enantioselective ⁇ -alkylation of the imines of formula (3) with the electrophilic olefins of formula (2) according to the present invention is carried out according to a general alkylation method already described for imines derived from non-chiral amines, for example: M. Pfau and C. Ribière, Chem. Comm., 66 (1970); Ibid. , Bull. Soc. Chim. Fr., 2584 (1971); Ibid., 776 (1976); B. de Jeso and J.-C. Pommier, Chem. Comm., 565 (1977); M. Pfau and J. Ughetto-Monfrin, Tetrahedron, 35, 1899 (1979); M. Pfau, J. Ughetto-Monfrin and D. Joulain, Bull. Soc. Chim. Fr. II, 627 (1979).
• the process for the preparation of the chiral imine compounds of the present invention is a new type of asymmetric induction by ⁇ alkylation of chiral copine imines with electrophilic olefins.
• At least one of the substituents in ⁇ of the imine function is functionalized, in particular by functions useful for subsequent synthesis steps: nitrile function, nitro, carbonyl, carboxylate, amide, sulfone, for example.
• the compounds of the present invention are thus very useful synthesis intermediates and make it possible to obtain natural synthetic compounds that the prior art did not make it possible to obtain.
• the compounds of formula (1) are obtained with an excellent chemical yield which is generally more than 80%.
• the optical purity of the compound obtained is very high. It generally reaches more than 90%.
• a product is obtained whose optical purity is 91 %.
• ketones obtained have a functionalized group chain (R 1 in formula (8)) located on the chiral carbon, making it possible, by various successive stages, to synthesize chiral compounds of great interest, such as octalones, ⁇ -spiranic compounds, etc. ., mentioned above.
• methyl-1 tetralone-2 is imitated by (-) - (S) -phenyl-1 ethylamine by the azeotropic method (benzene, 5 hours).
• the crude imine obtained is alkylated with methylvinylketone (THF, five days at room temperature), to give the addition imine of formula

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• Chemical & Material Sciences (AREA)
• Organic Chemistry (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
• Pyrane Compounds (AREA)
• Quinoline Compounds (AREA)
• Other In-Based Heterocyclic Compounds (AREA)

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• 1984
  • 1984-04-24 FR FR8406543A patent/FR2563216B1/fr not_active Expired
• 1985
  • 1985-04-23 WO PCT/FR1985/000092 patent/WO1985004873A1/fr not_active Application Discontinuation
  • 1985-04-23 EP EP19850902053 patent/EP0210171A1/de not_active Withdrawn
• 1986
  • 1986-09-24 JP JP61227071A patent/JPS6383055A/ja active Pending

Non-Patent Citations (1)

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