Methods of hydromethylation of alkenes and ketones

Patent metadata

Field	Value
Publication number	US-12049449-B2
Application number	US-202117385528-A
Country	US
Kind code	B2
Filing date	Jul 26, 2021
Priority date	Jul 26, 2021
Publication date	Jul 30, 2024
Grant date	Jul 30, 2024

Abstract

Methods of hydromethylation of alkenes and ketones, including methods that use Tebbe's reagent. The methods may include contacting Cp2Ti(μ-Cl)(μ-CH2)AlMe2 and an alkene or a ketone to produce an intermediate product that may include a titanacyclobutane. The intermediate product may be contacted with an acid to produce a methylated product.

First claim

The invention claimed is:

1. A method of hydromethylation, the method comprising:
contacting (i) an alkene, and (ii) Cp 2 Ti(μ-Cl)(μ-CH 2 )AlMe 2 to produce an intermediate product in a reaction mixture; and
contacting the intermediate product with an acid to produce a methylated product, wherein the intermediate product is not isolated from the reaction mixture prior to the contacting of the intermediate product with the acid;
wherein the alkene has a structure according to formula (I)—

wherein R 1 is a C 1 -C 20 hydrocarbyl, and R 2 and R 3 are hydrogen,
wherein the methylated product includes (i) a first product in which the carbon atom bonded to R 1 and R 2 is methylated, and (ii) a second product in which the carbon atom bonded to R 3 is methylated, and
wherein a mole ratio of the first product to the second product is about 3:1 to about 30:1.

2. The method of claim 1 , wherein the contacting of (i) the alkene and (ii) Cp 2 Ti(μ-Cl)(μ-CH 2 )AlMe 2 occurs in the presence of a Lewis base.

3. The method of claim 2 , wherein the Lewis base is selected from the group consisting of 4-dimethylaminopyridine and tetahydrofuran.

4. The method of claim 2 , wherein, relative to the alkene, the Lewis base is present at an amount equal to about 0.8 equivalents to about 1.2 equivalents.

5. The method of claim 1 , wherein the alkene is contacted with about 1 equivalent to about 1.5 equivalents of the Cp 2 Ti(μ-Cl)(μ-CH 2 )AlMe 2 .

6. The method of claim 1 , wherein the alkene is an exocyclic alkene or an endocyclic alkene.

7. The method of claim 6 , wherein the exocyclic alkene or the endocyclic alkene is tri-substituted.

8. The method of claim 1 , wherein the acid is selected from the group consisting of a hydrogen halide and a trihaloacetic acid.

9. The method of claim 1 , wherein the contacting of (i) the alkene and (ii) Cp 2 Ti(μ-Cl)(μ-CH 2 )AlMe 2 occurs at a temperature less than 30° C.

10. The method of claim 1 , wherein the contacting of (i) the alkene and (ii) Cp 2 Ti(μ-Cl)(μ-CH 2 )AlMe 2 occurs at a temperature of about −10° C. to about 10° C.

11. The method of claim 1 , wherein the contacting of (i) the alkene and (ii) Cp 2 Ti(μ-Cl)(μ-CH 2 )AlMe 2 occurs under an inert gas.

12. A method of hydromethylation, the method comprising:
contacting (i) an alkene, and (ii) Cp 2 Ti(μ-Cl)(μ-CH 2 )AlMe 2 at a temperature less than 30° C. in the presence of a Lewis base to produce an intermediate product in a reaction mixture, the intermediate product comprising a titanacyclobutane moiety; and
contacting the intermediate product with an acid to produce a methylated product, wherein the intermediate product is not isolated from the reaction mixture prior to the contacting of the intermediate product with the acid;
wherein the alkene has a structure according to formula (I)—

wherein R 1 is a C 1 -C 20 hydrocarbyl, and R 2 and R 3 are hydrogen,
wherein the methylated product includes (i) a first product in which the carbon atom bonded to R 1 and R 2 is methylated, and (ii) a second product in which the carbon atom bonded to R 3 is methylated, and
wherein a mole ratio of the first product to the second product is about 3:1 to about 30:1.

13. The method of claim 12 , wherein the Lewis base is selected from the group consisting of 4-dimethylaminopyridine and tetahydrofuran.

14. The method of claim 12 , wherein the mole ratio of the first product to the second product is about 6:1 to about 25:1.

15. The method of claim 1 , wherein the mole ratio of the first product to the second product is about 6:1 to about 25:1.

16. The method of claim 1 , wherein R 1 is selected from the group consisting of—

17. The method of claim 12 , wherein R 1 is selected from the group consisting of—

Assignees

• Univ Florida State Res Found Inc

Inventors

• Frederich James H
• Law James A

Classifications

• C07C239/10

  having nitrogen atoms of hydroxylamino groups further bound to carbon atoms of unsubstituted hydrocarbon radicals or of hydrocarbon radicals substituted by halogen atoms or by nitro or nitroso groups · CPC title

• C07C41/30

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

• C07C17/272

  by addition reactions · CPC title

• C07C2531/14

  of aluminium or boron · CPC title

• C07C1/327

  the hetero-atom being an aluminium atom (C07C2/88 takes precedence) · CPC title