EP-4735616-A2 - PROCESS FOR PREPARING GAMMA,DELTA-UNSATURATED ALDEHYDES DERIVATIVES

Abstract

The present invention relates to the field of organic synthesis and more specifically it concerns a process for preparing compound of formula (II) starting from compound of formula (I) and a process for preparing compound of formula (I) via valuable new chemical intermediates such as compound of formula (IV) and the compound of formula (V). The compound (IV) and the compound of formula (V) are also part of the invention.

Inventors

• STEINER, KERSTIN
• MOSIMANN, Hervé

Assignees

• Firmenich SA

Dates

Publication Date

20260506

Application Date

20240621

Claims (1)

1. Firmenich SA 120 Claims 1. A process for the reduction by hydrogenation of conjugated dienal of formula in the form of any and wherein each R 1 , 2 3 R and R , a atom, a C1-3 alkoxy group, a C 1-6 alkyl group or a C 2-6 alkenyl group, each optionally substituted by a hydroxy or C1-3 alkoxy group; or R 1 and R 2 , are taken together and form a C3-8 cycloalkyl or C 5-8 cycloalkenyl group; R 4 , R 5 and R 6 , independently from each other, are a hydrogen atom, a methyl or an ethyl group; into a deconjugated enal of formula in the form of any and wherein R 1 to R 6 have the same meaning as defined in formula (I); said process being carried out in the presence of an oxidoreductase. 2. The process according to claim 1, wherein the oxidoreductase enzyme is an ene reductase. 3. The process according to claim 2, wherein the ene reductase enzyme has at least 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 96%, 97%, 98% or 99% sequence identity of any of SEQ ID NOs: 1 to 44. Firmenich SA 121 4. The process according to any the previous claims, wherein the reduction is performed in the presence of a cofactor; preferably the cofactor is selected from the group of NADPH, NADP + , NADH and NAD + . 5. The process according to any one of the previous claims, wherein the reduction is performed in the presence of a cofactor regeneration system. 6. The process according to any one of the previous claims, wherein the process is an in vivo or in vitro process. 7. The process according to any one of the previous claims, wherein R 5 is a methyl group; R 4 and R 6 are hydrogen atoms and R 1 , R 2 and R 3 , independently from each other, represent a hydrogen atom or a C 1-3 alkyl group. 8. The process according to any one of the previous claims, wherein the compound of formula (I) is of formula in the form of any and wherein each R 1 and R 2 have the same as or claim 7; and said compound of formula (II) is of formula in the form of and wherein each R 1 and R 2 have the same as or claim 7. 9. A process for the preparation of a compound of formula Firmenich SA 122 in the form of any one of its or a mixture thereof, and wherein each R 1 , R 2 and R 3 , independently from each other, represent a hydrogen atom, a C 1-3 alkoxy group, a C1-6 alkyl group or a C2-6 alkenyl group, each optionally substituted by a hydroxy or C 1-3 alkoxy group; or R 1 and R 2 , are taken together and form a C 3-8 cycloalkyl or C5-8 cycloalkenyl group; R 4 , R 5 and R 6 , independently from each other, are a hydrogen atom, a methyl or an ethyl group; comprising the steps of a) converting a compound of formula in the form of thereof, and wherein R 1 , R 2 , R 3 , R 4 and R 5 have the same meaning as defined in formula (I); into an acetal of formula in the thereof, and wherein R 1 , R 2 , R 3 , R 4 and R 5 have the same meaning as defined in formula (I); R a and R b , independently from each other, represent a C1-4 alkyl group or R a and R b , when taken together, represent a C 2-5 alkanediyl group; b) treating the acetal obtained in step a) with an acid and a compound of formula R 6 -CH=CH-OR c ; wherein R 6 has the same meaning as defined in formula (I) and R c represents a C 1-4 alkyl group; to obtain a compound of formula Firmenich SA 123 in the form thereof, and wherein R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R a , R b and R c have the same meaning as defined above; and c) treating the compound of formula (V) with an acid to obtain a compound of formula (I). 10. The process according to claim 9, wherein R a and R b , independently from each other, represent a C 1-3 alkyl group and R c is a methyl or ethyl group; preferably R a and R b , independently from each other, represent a methyl group. 11. The process according to any one of claims 9 to 10, wherein step a) is carried out in the presence of an acid and a reagent selected from the group consisting of C 1-4 trialkyl orthoformate, C1-4 alcohol and C2-5 diol. 12. The process according to any one of claims 9 to 11, wherein the acid used in step b) is selected from the group consisting of boron trifluoride complexes, anhydrous zinc chloride, and para toluene sulfonic acid. 13. The process according to any one of claims 9 to 12, wherein the acid used in step c) is selected from the group consisting of formic acid, acetic acid, aqueous acetic acid, propionic acid, aqueous sulfuric acid, sulfuric acid and aqueous hydrochloric acid. 14. A compound of formula Firmenich SA 124 in the form of the 1 2 reof, and wherein R , R and R 3 , independently from each other, represent a hydrogen atom, a C 1-3 alkoxy group, a C1-6 alkyl group or a C2-6 alkenyl group, each optionally substituted by a hydroxy or C 1-3 alkoxy group; or R 1 and R 2 , are taken together and form a C 3-8 cycloalkyl or C5-8 cycloalkenyl group; R 4 and R 5 , independently from each other, are a hydrogen atom, a methyl or an ethyl group; R a and R b , independently from each other, represent a C1-4 alkyl group or R a and R b , when taken together, represent a C2- 5 alkanediyl group. 15. A compound of formula in the form of and wherein R 1 2 , R and R 3 , independently from each other, represent a hydrogen atom, a C1-3 alkoxy group, a C 1-6 alkyl group or a C 2-6 alkenyl group, each optionally substituted by a hydroxy or C1-3 alkoxy group; or R 1 and R 2 , are taken together and form a C3-8 cycloalkyl or C 5-8 cycloalkenyl group; R 4 , R 5 and R 6 , independently from each other, are a hydrogen atom, a methyl or an ethyl group; R a and R b , independently from each other, represent a C 1-4 alkyl group or R a and R b , when taken together, represent a C2-5 alkanediyl group; R c represents a C1-4 alkyl group.

Description

Firmenich SA 1 PROCESS FOR PREPARING GAMMA,DELTA-UNSATURATED ALDEHYDES DERIVATIVES Technical field The present invention relates to the field of organic synthesis and more specifically it concerns a process for preparing compound of formula (II) starting from compound of formula (I) and a process for preparing compound of formula (I) starting from compound of formula (III) via valuable new chemical intermediates such as compound of formula (IV) and the compound of formula (V). The compound (IV) and the compound of formula (V) are also part of the invention. Background of the invention In the perfumery industry, there is a constant need to provide compounds imparting novel organoleptic notes. In particular, there is an interest towards ingredients imparting the lily of the valley odor or at least one of the key organoleptic facets of the lily of the valley odor. So, compounds imparting said note are particularly sought after to reconstitute the delicate floral odor of muguet which does not survive even the mildest of extraction methods to yield an essential oil. Towards this goal, compounds of formula (II) were previously reported in WO2010/052635 or in WO2015/000821. Said compounds have been prepared via a Johnson-Claisen rearrangement followed by reduction and oxidations requesting non catalytic and toxic reagents such as hydride or pyridinium chlorochromate or directly via a Claisen rearrangement. However, the rearrangement step provides the desired intermediate or product with moderate to low yield. Being products of industrial interest, there is always a need for new processes showing an improved yield and productivity. In the meantime, today there is a need to foster sustainable processes, for examples using enzymatic transformation. The present invention allows to solve the above problems by using an oxidoreductase in the process to prepare compound of formula (II). The process herein disclosed represents a novel route through novel intermediates, never disclosed before, while improving yield and environmental impact. To the best of our knowledge, the invention’s conditions and the compounds of formula (IV) and (V) which are an object of the present invention, have never been reported in the prior art. Firmenich SA 2 Summary of the Invention The invention relates to a novel process allowing the preparation of compound of formula (II) with a high yield and high selectivity starting from compound of formula (III) via compound of formula (IV), (V) and (I). The invention process represents a new efficient route toward compound of formula (II). So, the first object of the present invention is a process for the reduction by hydrogenation of conjugated dienal of formula in the form of any and wherein each R1, R2 3 and R , a atom, a C1-3 alkoxy group, a C1-6 alkyl group or a C2-6 alkenyl group, each optionally substituted by a hydroxy or C1-3 alkoxy group; or R1 and R2, are taken together and form a C3-8 cycloalkyl or C5-8 cycloalkenyl group; R4, R5 and R6, independently from each other, are a hydrogen atom, a methyl or an ethyl group; into a deconjugated enal of formula in the form of any one and wherein R1 to R6 have the same meaning as defined in formula (I); said process being carried out in the presence of an oxidoreductase. A second object of the present invention is a process for the preparation of a compound of formula Firmenich SA 3 in the form of any one of its or a mixture thereof, and wherein each R1, R2 and R3, independently from each other, represent a hydrogen atom, a C1-3 alkoxy group, a C1-6 alkyl group or a C2-6 alkenyl group, each optionally substituted by a hydroxy or C1-3 alkoxy group; or R1 and R2, are taken together and form a C3-8 cycloalkyl or C5-8 cycloalkenyl group; R4, R5 and R6, independently from each other, are a hydrogen atom, a methyl or an ethyl group; comprising the steps of a) converting a compound of formula in the form of thereof, and wherein R1, R2, R3, R4 and R5 have the same meaning as defined in formula (I); into an acetal of formula in the form of 1 thereof, and wherein R , R2, R3, R4 and R5 have the same meaning as defined in formula (I); Ra and Rb, independently from each other, represent a C1-4 alkyl group or Ra and Rb, when taken together, represent a C2-5 alkanediyl group; b) treating the acetal obtained in step a) with an acid and a compound of formula R6-CH=CH-ORc; wherein R6 has the same meaning as defined in formula (I) and Rc represents a C1-4 alkyl group; to obtain a compound of formula Firmenich SA 4 in the form of any one 1 2 3 and wherein R , R , R , R4, R5, R6, Ra, Rb and Rc have the same meaning as defined above; and c) treating the compound of formula (V) with an acid to obtain a compound of formula (I). A third object of the present invention is a compound of formula in the form of any one 1 2 and wherein R , R and R3, independently from each other, represent a hydrogen atom, a C1-3 alkoxy group, a C1-6 alkyl group or a C2