Search

JP-7855723-B2 - Hydrogenation method of unsaturated esters

JP7855723B2JP 7855723 B2JP7855723 B2JP 7855723B2JP-7855723-B2

Inventors

  • グレインジャー，ダミアン
  • バジャリア，クリシャ

Assignees

  • ジョンソン、マッセイ、パブリック、リミテッド、カンパニー

Dates

Publication Date
20260508
Application Date
20230503
Priority Date
20220503

Claims (17)

  1. A method for producing an alcohol of formula (II) by hydrogenating an ester-containing substrate of formula (I), The method comprises treating an ester-containing substrate of formula (I) with a base and a transition metal catalyst in the presence of molecular hydrogen, wherein the transition metal in the transition metal catalyst is Ru. The ester-containing substrate of formula (I) includes α,β-γ,δ unsaturated esters or β,γ unsaturated esters; Ru is an organic group having 3 to 70 carbon atoms, provided that Ru is bonded to the carbonyl carbon ( * ) of an ester to form an α,β-γ,δ unsaturated ester or β,γ unsaturated ester of formula (I); A method wherein R v is an organic group having 1 to 70 carbon atoms, and the conjugate acid of the base has a pKa of 4 to 15.
  2. R u is given by equation (XII): (In the formula, the dashed lines indicate the bond of the ester portion of the ester-containing substrate in formula (I) to the carbonyl carbon ( * ); The method according to claim 1, wherein R5 to R8 are each independently an organic group having a hydrogen atom or 1 to 70 carbon atoms, and R9 is an organic group having H or 1 to 70 carbon atoms.
  3. R u is given by equation (XIII): (In the formula, the dashed lines indicate the bond of the ester portion of the ester-containing substrate in formula (I) to the carbonyl carbon ( * ); The method according to claim 1, wherein R10 to R12 are each independently an organic group having a hydrogen atom or 1 to 70 carbon atoms, and R13 is an organic group having H or 1 to 70 carbon atoms.
  4. The method according to claim 1, wherein Ru is an organic group having formula (XII) or formula (XIII) as defined in claim 2 or claim 3.
  5. The method according to claim 1, wherein the ester-containing substrate of formula (I) is an alkyl sorbate or an alkyl trans-3-hexanoate.
  6. The method according to any one of claims 1 to 3, 5, wherein the alcohol of formula (II) is trans,trans-hexa-2,4-dien-1-ol or trans-hexa-3-en-1-ol.
  7. The method according to any one of claims 1 to 3, 5, wherein the conjugate acid of the base has a pKa of 5 to 14 .
  8. The method according to any one of claims 1 to 3, or 5, wherein the base is a metal phosphate or a metal carbonate.
  9. The method according to any one of claims 1 to 3, 5, wherein the base is an alkali metal phosphate, an alkaline earth metal phosphate, an alkali metal carbonate, or an alkaline earth metal carbonate.
  10. The method according to any one of claims 1 to 3, 5, wherein the base is lithium phosphate (Li 3 PO 4 ), sodium phosphate (Na 3 PO 4 ), potassium phosphate (K 3 PO 4 ), or cesium phosphate (Cs 3 PO 4 ).
  11. The method according to any one of claims 1 to 3, or 5, wherein the base exists in a solid form.
  12. The method according to any one of claims 1 to 3, or 5, wherein the base is present in an amount of 30 to 70 mol% of the total amount of the ester-containing substrate, 30 to 60 mol% of the total amount of the ester-containing substrate, or 30 to 50 mol% of the total amount of the ester-containing substrate.
  13. The method according to claim 1, wherein the transition metal catalyst comprises a tridentate ligand.
  14. The transition metal catalyst is a tridentate ligand having formula (III). (In the formula, X is selected from -SR a , -OR a , -CR a , -NR a R b , -PR a R b , -P(=O)R a R b , -OPR a R b , and -NHPR a R b ; R1 and Rx are each independently selected from hydrogen, substituted or unsubstituted C1-20 -alkyl, substituted or unsubstituted C2-20-alkenyl, substituted or unsubstituted C2-20 -alkynyl, substituted or unsubstituted C1-20 -heteroalkyl, substituted or unsubstituted C1-20 -alkoxy, substituted or unsubstituted C3-20 -cycloalkyl, substituted or unsubstituted C3-20 -cycloalkenyl, substituted or unsubstituted C2-20 -heterocycloalkyl, substituted or unsubstituted C6-20 -aryl, and substituted or unsubstituted C4-20 -heteroaryl; or R1 and one of R3a and R3b , or Rx and one of R3a and R3b , together with the atom to which they are bonded; Alternatively, X is a heteroatom, and if R x is not present, it combines with R 1 to form a heteroring that is optionally substituted; Y is selected from -SR a , -OR a , -CR a , -NR a R b , -PR a R b , -P(=O)R a R b , -OPR a R b , and -NHPR a R b ; R2 and Ry are each independently selected from hydrogen, substituted or unsubstituted C1-20 -alkyl, substituted or unsubstituted C2-20-alkenyl, substituted or unsubstituted C2-20 -alkynyl, substituted or unsubstituted C1-20 -heteroalkyl, substituted or unsubstituted C1-20 -alkoxy, substituted or unsubstituted C3-20 -cycloalkyl, substituted or unsubstituted C3-20 -cycloalkenyl, substituted or unsubstituted C2-20 -heterocycloalkyl, substituted or unsubstituted C6-20 -aryl, and substituted or unsubstituted C4-20 -heteroaryl, or R2 and one of R4a and R4b , or Ry and one of R4a and R4b , together with the atom to which they are bonded; Alternatively, Y is a heteroatom, and if R y is not present, it combines with R 2 to form a heteroring that is optionally substituted; R 3a , R 3b , R 4a , and R 4b are each independently selected from hydrogen, substituted or unsubstituted C1-20 -alkyl, substituted or unsubstituted C2-20-alkenyl, substituted or unsubstituted C2-20 -alkynyl, substituted or unsubstituted C1-20 -heteroalkyl, substituted or unsubstituted C1-20 -alkoxy, substituted or unsubstituted C3-20 -cycloalkyl, substituted or unsubstituted C3-20 -cycloalkenyl, substituted or unsubstituted C2-20 -heterocycloalkyl, substituted or unsubstituted C6-20 -aryl, and substituted or unsubstituted C4-20 -heteroaryl; or R 3a and one of R 4a and R 4b , or R 3b and R 4a and R One of 4b forms a heteroring with the atom to which they are bonded; R 5 is selected from hydrogen, substituted or unsubstituted C1-20 -alkyl, substituted or unsubstituted C2-20-alkenyl, substituted or unsubstituted C2-20 -alkynyl, substituted or unsubstituted C1-20 -heteroalkyl, substituted or unsubstituted C1-20 -alkoxy, substituted or unsubstituted C3-20 -cycloalkyl, substituted or unsubstituted C3-20 -cycloalkenyl, substituted or unsubstituted C2-20 -heterocycloalkyl, substituted or unsubstituted C6-20 -aryl, and substituted or unsubstituted C4-20 -heteroaryl ; Each m and n is independently 1 or 2; and R a and R b , if present, are independently selected from hydrogen, substituted or unsubstituted C1-20 -alkyl, substituted or unsubstituted C2-20-alkenyl, substituted or unsubstituted C2-20 -alkynyl, substituted or unsubstituted C1-20 -heteroalkyl, substituted or unsubstituted C1-20 -alkoxy, substituted or unsubstituted C3-20 -cycloalkyl, substituted or unsubstituted C3-20 -cycloalkenyl, substituted or unsubstituted C2-20 -heterocycloalkyl, substituted or unsubstituted C6-20 -aryl, and substituted or unsubstituted C4-20 -heteroaryl; or X and/or Y is -NR a R b , -PR a R b , -OPR a R b or -NHPR a R The method according to claim 13, wherein if b is present, R a and R b form a heteroring together with the heteroatom to which they are bonded.
  15. The transition metal catalyst is of formula (IV) or formula (V) [M(L 1 )(L 2 ) d ] (IV) [M(L 1 )(L 2 ) d ]W (V) (In the formula, M is a transition metal , and the transition metal in the transition metal catalyst is Ru ; L1 is a tridentate ligand as defined in claim 14; L2 is a ligand that may be the same or different; The method according to any one of claims 1 to 3, 5, wherein d is 1, 2, or 3; and W is a non-coordinating anion ligand .
  16. The method according to claim 15, wherein each L 2 is independently selected from -H, -CO, -CN, -P(R') 3 , -As(R') 3 , -CR', -OR', -O(C=O)R', -NR' 2 , halogens (e.g., -Cl, -Br, -I), and solvents, wherein each R' is independently selected from substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted alkoxy, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, and substituted or unsubstituted heteroaryl.
  17. The transition metal catalyst, The method according to any one of claims 1 to 3 or 5.

Description

Technical field to which the invention pertains: The present invention relates to a method for hydrogenating ester-containing substrates. More specifically, the present invention relates to a method for reducing α,β-γ,δ unsaturated esters and β,γ unsaturated esters. Background of the Invention Ester reduction is an essential conversion in the chemical industry as a pathway to primary alcohols. Conventionally, ester reduction has been carried out using reagents such as sodium metal in ethanol (in stoichiometric or excess amounts) (Bouveault-Blanc reduction), or more recently, using metal hydride reagents such as LiAlH₄ and NaBH₄ . However, these reduction reactions are difficult to carry out on a large scale and effectively, particularly due to safety concerns associated with the extremely exothermic quenching process. Thus, research on ester reduction has more recently focused on catalytic reduction using hydrogen gas. For example, Cu or Zn-based heterogeneous catalysts are used very extensively for ester reduction, mainly in the natural detergent alcohol (NDA) market. However, these methods require very high pressure and/or temperature in addition to large-scale dedicated manufacturing facilities. Furthermore, the chemoselectivity of ester reduction compared to other highly sensitive functional groups can be a problem when using these methods. The reduction of unsaturated esters, such as α,β-γ,δ unsaturated esters and β,γ unsaturated esters, can be particularly problematic. Finding conditions for chemoselective reduction of the ester group while maintaining the regiochemistry of the alkenyl functional group is especially difficult. For ease of understanding, α, β, γ, and δ, when used in the context of unsaturated esters, refer to carbon atoms in the ester-containing substrate. α, β, γ, and δ are used to indicate carbon atoms in which alkene (C=C) or alkyne (C≡C) bonds exist. Scheme 1 below shows the positions of α, β, γ, and δ carbons in a typical ester-containing substrate, and this notation rule will be used herein and throughout. Therefore, for example, a β,γ-unsaturated ester contains an alkene bond between the β carbon and the γ carbon, while an α,β-γ,δ unsaturated ester contains two alkene bonds (i.e., an alkene bond between the α carbon and the β carbon, and an alkene bond between the γ carbon and the δ carbon). Many methods for esterification hydrogenation using transition metal catalysts have been developed, but these methods often result in reduction of the alkenyl functional group or a regiochemical change of the alkenyl functional group. Therefore, there is still a need for a method that can selectively reduce unsaturated esters, particularly α,β-γ,δ unsaturated esters and β,γ unsaturated esters, while maintaining the regiochemistry of alkenyl functional groups. Therefore, the present invention provides a method for hydrogenating α,β-γ,δ unsaturated esters or β,γ unsaturated esters. This method exhibits high chemoselectivity for hydrogenating the ester groups of α,β-γ,δ unsaturated esters and β,γ unsaturated esters to the corresponding alcohols while maintaining the regiochemistry and/or stereochemistry of the alkenyl and/or alkynyl functional groups. In a first aspect of the present invention, a method is provided for producing an alcohol of formula (II) by hydrogenating an ester-containing substrate of formula (I), The above method includes treating an ester-containing substrate of formula (I) with a base and a transition metal catalyst in the presence of molecular hydrogen. The ester-containing substrate of formula (I) includes α,β-γ,δ unsaturated esters or β,γ unsaturated esters; Ru is an organic group having 3 to 70 carbon atoms, provided that Ru is bonded to the carbonyl carbon ( * ) of the ester moiety to form an α,β-γ,δ unsaturated ester or β,γ unsaturated ester of formula (I); R v is an organic group having 1 to 70 carbon atoms; The conjugate acid of a base has a pKa of 4 to 15. A remarkable advantage of the present invention is that the hydrogenation of α,β-γ,δ unsaturated esters or β,γ unsaturated esters proceeds without reduction of the alkenyl functional group of the Ru group, and the regiochemistry and/or stereochemistry of the Ru group is maintained between the ester-containing substrate of formula (I) and the alcohol of formula (II). In other words, the Ru group is the same in the ester-containing substrate of formula (I) and the alcohol of formula (II). The conjugate acid of the base of the present invention has a pKa of 4 to 15 and can be considered a weak base. While we do not wish to be bound by any theory, it is thought that in the hydrogenation method of the present invention, by using a base with a conjugate acid pKa of 4 to 15, conjugation between the carbonyl group and the alkenyl functional group is prevented, and the formation of an enolate intermediate is minimized or prevented. It is presumed that the formation of such an enolate intermediate may be the cause of re