US2017283342A1PendingUtilityA1

Organic compounds

43
Assignee: GIVAUDAN SAPriority: Oct 25, 2013Filed: Jun 22, 2017Published: Oct 5, 2017
Est. expiryOct 25, 2033(~7.2 yrs left)· nominal 20-yr term from priority
Inventors:Fridtjof SchröderFabian Ruethi
C07B 37/08C07C 2602/50C07C 2531/22C07C 2/86C07C 45/69C07C 41/30C07C 2601/16B01J 2531/824B01J 31/2213C07C 2601/02C07C 67/347C07B 37/02B01J 2231/324C07C 49/553C07C 13/04C07C 43/21C07C 69/608
43
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Claims

Abstract

A process of converting a carbon-carbon multiple bond to a cyclopropane ring, comprising the addition of a N-alkyl-N-nitroso compound to a mixture of alkene precursor, aqueous base and Pd(II)-catalyst, with the N-alkyl-N-nitroso compound obtained directly from an alkyl amine derivative, NaNO 2 and an acid via phase separation of the N-alkyl-N-nitroso compound from the aqueous phase.

Claims

exact text as granted — not AI-modified
1 . A process of ring formation across a carbon-carbon multiple bond, the process comprising reacting a N-methyl-N-nitroso compound with a substrate bearing a carbon-carbon multiple bond, wherein the N-methyl-N-nitroso compound has been generated in-situ, and the generated N-methyl-N-nitroso compound is reacted with the substrate via in-situ-generated diazomethane, without being first isolated. 
     
     
         2 . The process according to  claim 1 , wherein the N-methyl-N-nitroso compound is an organic solution of N-methyl-N-nitroso urea, and wherein the N-methyl-N-nitroso urea is reacted with the substrate without being first isolated in solid form. 
     
     
         3 . The process according to  claim 1 , wherein the N-methyl-N-nitroso compound is selected from the group consisting of N-methyl-N-nitroso-urea (MNU), N-methyl-N-nitroso-p-toluenesulfonamide, N-nitroso-dimethylurethane, nitroso-EMU and N-nitroso-β-methylaminoisobutyl methyl ketone (NMK). 
     
     
         4 . The process according to  claim 1 , wherein the N-methyl-N-nitroso compound is generated in-situ from a mixture of a HNRR′ compound, water, NaNO 2  and an acid, before partitioning into an organic solvent to form an organic solution of N-methyl-N-nitroso compound. 
     
     
         5 . The process according to  claim 4  wherein the N-methyl-N-nitroso compound is formed in-situ from a N-methylamine. 
     
     
         6 . The process according to  claim 1 , wherein the N-methyl-N-nitroso compound is reacted with the substrate bearing a carbon-carbon multiple bond via the diazomethane in the presence of an aqueous base and a catalyst. 
     
     
         7 . The process according to  claim 6 , wherein the aqueous base is selected from the group consisting of alkali hydroxides. 
     
     
         8 . The process according to  claim 6 , wherein the catalyst is a transition metal catalyst, optionally a palladium catalyst, further optionally Pd(acac) 2 , Pd(OAc) 2  or PdCl 2  catalysts. 
     
     
         9 . The process according to  claim 1 , wherein a biphasic mixture is formed with the N-methyl-N-nitroso compound in an organic layer. 
     
     
         10 . The process according to  claim 1 , wherein the N-methyl-N-nitroso compound in liquid phase is separated from an aqueous phase in a phase separation step, before being reacted with the substrate bearing a carbon-carbon multiple bond. 
     
     
         11 . The process according to  claim 1 , wherein the N-methyl-N-nitroso compound has been generated in a liquid phase comprising an organic solvent for the N-methyl-N-nitroso compound that is selected from the group consisting of ethers and toluene. 
     
     
         12 . The process according to  claim 11  wherein the ether is selected from the group consisting of tetrahydrofurane, dimethoxyethane, dioxane and dimethylisosorbide. 
     
     
         13 . The process according to  claim 1 , which is conducted in flow mode. 
     
     
         14 . The process according to  claim 1 , wherein the substrate bearing a carbon-carbon multiple bond is a terminal (monosubstituted) alkene. 
     
     
         15 . The process according to  claim 14 , wherein the substrates are isoprenoids. 
     
     
         16 . The process according to  claim 1 , wherein the substrate bearing a carbon-carbon multiple bond is a compound of the formulae 
       
         
           
           
               
               
           
         
         wherein R 1  and R 2  may, independently of each other, be hydrogen, alkyl, alkylidene, or aryl, which may be branched or unbranched and substituted or unsubstituted; 
         and R 3  may be an alkyl, alkylidene, or aryl, which may be branched or unbranched and substituted or unsubstituted. 
       
     
     
         17 . The process according to  claim 1 , wherein the substrate is myrcene, ocimene, farnesene or a higher polyprenoid, wherein the substrate becomes a mono- or bis-cyclopropanated derivative at the terminal isoprene unit with >70% selectivity. 
     
     
         18 . The process according to  claim 17 , yielding a myrcene, ocimene, farnesene or higher polyprenoid derivative which is mono- or bis-cyclopropanated at the terminal isoprene unit with >80% selectivity. 
     
     
         19 . The process according to  claim 17 , yielding a myrcene, ocimene, farnesene or higher polyprenoid derivative which is mono- or bis-cyclopropanated at the terminal isoprene unit with >90% selectivity. 
     
     
         20 . A process of converting a carbon-carbon double bond to a cyclopropane ring comprising:
 I) synthesis of a N-methyl-N-nitroso compound in liquid phase,   II) separation of an organic N-methyl-N-nitroso compound-containing liquid phase from an aqueous phase, and   III) transferring the N-methyl-N-nitroso compound in the organic liquid phase into a mixture comprising an alkene substrate, thereby to cyclopropanate the alkene substrate.   
     
     
         21 . The process according to  claim 20 , wherein the mixture further comprises aqueous base and catalyst. 
     
     
         22 . The process according to  claim 20 , wherein the substrate is myrcene, ocimene, farnesene or a higher polyprenoid, yielding a mono- or bis-cyclopropanated derivative at the terminal isoprene unit with >70% selectivity. 
     
     
         23 . The process according to  claim 22 , yielding a myrcene, ocimene, farnesene or higher polyprenoid derivative which is mono- or bis-cyclopropanated at the terminal isoprene unit with >80% selectivity. 
     
     
         24 . The process according to  claim 22 , yielding a myrcene, ocimene, famesene or higher polyprenoid derivative which is mono- or bis-cyclopropanated at the terminal isoprene unit with >90% selectivity. 
     
     
         25 . The process according to  claim 20 , wherein the substrate is ethyl decenoate, yielding ethyl 8-cyclopropyloctanoate. 
     
     
         26 . The process according to  claim 20 , wherein the substrate is 1-spiro(4.5)-7-decen-7-yl)-4-penten-1-one and 1-spiro(4.5)-6-decen-7-yl)-4-penten-1-one, yielding 3-cyclopropyl-1-(spiro[4.5]dec-7-en-7-yl)propan-1-one and 3-cyclopropyl-1-(spiro[4.5]dec-6-en-7-yl) propan-1-one. 
     
     
         27 . The process according to  claim 20 , wherein the substrate is 1-methyl-3-vinylbenzene, yielding 1-cyclopropyl-3-methylbenzene. 
     
     
         28 . The process according to  claim 20 , wherein the substrate is estragol, yielding 1-cyclopropylmethyl-4-methoxybenzene.

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