Organic compounds

Patent metadata

Field	Value
Publication number	US-9718741-B2
Application number	US-201415031158-A
Country	US
Kind code	B2
Filing date	Oct 24, 2014
Priority date	Oct 25, 2013
Publication date	Aug 1, 2017
Grant date	Aug 1, 2017

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.

First claim

The invention claimed is:

1. A process of ring formation across a carbon-carbon multiple bond, the process comprising the steps of reacting a N-alkyl-N-nitroso compound with a substrate bearing a carbon-carbon multiple bond, wherein the N-alkyl-N-nitroso compound has been generated in-situ, and the generated N-alkyl-N-nitroso compound is reacted with the substrate without being first isolated.

2. The process according to claim 1 , wherein the N-alkyl-N-nitroso compound is an organic solution of N-alkyl-N-nitroso urea, and wherein the N-alkyl-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-alkyl-N-nitroso compound is a N-methyl-N-nitroso compound (MNC).

4. The process according to claim 1 , wherein the N-alkyl-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).

5. The process according to claim 1 , wherein the N-alkyl-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-alkyl-N-nitroso compound.

6. The process according to claim 5 wherein the N-alkyl-N-nitro compound is formed in-situ from a N-alkylamine.

7. The process according to claim 1 , wherein a biphasic mixture is formed with the N-alkylN-nitroso compound in an organic layer.

8. The process according to claim 1 , wherein the N-alkyl-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.

9. The process according to claim 1 , wherein the N-alkyl-N-nitroso compound is reacted with the substrate bearing a carbon-carbon multiple bond in the presence of an aqueous base and a catalyst.

10. The process of converting a carbon-carbon double bond to a cyclopropane ring according to claim 1 .

11. A process of converting a carbon-carbon double bond to a cyclopropane ring comprising the steps of:
I) synthesis of a N-alkyl-N-nitroso compound in liquid phase,
II) separation of an organic N-alkyl-N-nitroso compound-containing liquid phase from an aqueous phase, and
III) transferring the N-alkyl-N-nitroso compound in the organic liquid phase into a mixture comprising an alkene substrate, thereby to cyclopropanate the alkene substrate, wherein the alkene substrate is a terminal (monosubstituted) isoprenoid alkene.

12. The process according to claim 6 , wherein the N-alkylamine is methyl, ethyl, propyl or higher alkyl amine, which may be substituted or unsubstituted and linear or branched.

13. The process according to claim 3 , wherein a liquid phase comprises an organic solvent for the MNC that is selected from the group consisting of ethers and toluene.

14. The process according to claim 13 wherein the ether is selected from the group consisting of tetrahydrofurane, dimethoxyethane, dioxane and dimethylisosorbide.

15. The process according to claim 9 , wherein the aqueous base is selected from the group consisting of alkali hydroxides.

16. The process according to claim 9 , wherein the catalyst is a transition metal catalyst, optionally a palladium catalyst, further optionally Pd(acac) 2 , Pd(OAc) 2 or PdCl 2 catalysts.

17. The process according to claim 1 , which is conducted in flow mode.

18. The process according to claim 1 , wherein the substrate bearing a carbon-carbon multiple bond is a terminal (monosubstituted) alkene.

19. 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.

20. The process according to claim 18 , wherein the substrates are isoprenoids.

21. A compound according to the formula

in which n=1 or 3.

22. A compound according to claim 21 comprising

Assignees

• Givaudan Sa
• Amyris Inc
• Amyris Inc

Inventors

• Schroeder Fridtjof
• Ruethi Fabian

Classifications

• C07C45/69

  by addition to carbon-to-carbon double or triple bonds · CPC title

• C07C67/347 Primary

  by addition to unsaturated carbon-to-carbon bonds · CPC title

• C07B37/08

  Isomerisation · CPC title

• C07C41/30

  by increasing the number of carbon atoms, e.g. by oligomerisation · CPC title

• B01J2231/324

  Cyclisations via conversion of C-C multiple to single or less multiple bonds, e.g. cycloadditions · CPC title