Preparation of α-hydroxy ketones via carbene-catalyzed umpolung reaction of aldehydes

1. In a method for the preparation of α-hydroxy ketones by acyloin addition of aldehydes, the improvement comprising catalyzing said addition using a catalyst of formula II or III:

wherein:

R 1 and R 2 are the same or different and are each a C 6 -C 10 -aryl, heteroaryl, branched or unbranched, optionally mono- or poly-C 1 -C 4 -alkyl- or -heteroalkyl-substituted C 1 -C 10 -alkyl, C 3 -C 6 -cycloalkyl or mono- or poly-C 1 -C 4 -alkyl-substituted C 6 -C 10 -aryl, and

R 3 and R 4 are the same or different and are each hydrogen, branched or unbranched C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 6 -C 10 -aryl or heteroaryl.

2. A compound of formula IV:

wherein R5 and R6 are the same or different and are each a poly-C 1 -C 4 -alkyl-substituted C 6 -C 10 -aryl, or poly-C 1 -C 4 -alkyl-substituted C 1 -C 10 -alkyl, and

R7 and R8 are the same or different and are each a branched or unbranched C 1 -C 6 -alkyl.

3. The compound of claim 2 , wherein:

a) R5, R6 or both R5 and R6 are mesityl; and

b) R7, R8 or both R7 and R8 are methyl.

4. A process for preparing α-hydroxy ketones of formula I:

comprising reacting a carbonyl compound of the general formula RR′C═O with a carbonyl compound of the general formula HR″C═O, in the presence of a catalyst of formula II, III or IV:

wherein:

R 1 and R 2 are the same or different and are each a C 6 -C 10 -aryl, heteroaryl, branched or unbranched, optionally mono- or poly-C 1 -C 4 -alkyl- or -heteroalkyl-substituted C 1 -C 10 -alkyl, C 3 -C 6 -cycloalkyl or mono- or poly-C 1 -C 4 -alkyl-substituted C 6 -C 10 -aryl,

R 3 and R 4 are the same or different and are each a hydrogen, branched or unbranched C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 6 -C 10 -aryl or heteroaryl,

R5 and R6 are the same or different and are each a C 6 -C 10 -aryl, mono- or poly-C 1 -C 4 -alkyl-substituted C 6 -C 10 -aryl, optionally mono- or poly-C 1 -C 4 -alkyl-substituted C 1 -C 10 -alkyl or C 3 -C 6 -cycloalkyl,

R7 and R8 are the same or different and are each a hydrogen or branched or unbranched C 1 -C 6 -alkyl,

R and R′ are the same or different and are each H or a straight-chain or branched and optionally substituted C 1 -C 12 -alkyl radical; and

R″ is H 3 CSCH 2 CH 2 , t-butyl, n-butyl, sec-butyl, n-propyl, i-propyl, an optionally heteroatom-substituted C 6 -C 18 -aryl, heteroaryl, C 6 -C 18 -arylalkyl, or heteroalkyl.

5. The process of claim 4 , wherein R″ is phenylmethyl, and wherein said phenyl may be heteroatom-substituted.

6. The process of claim 4 , wherein said catalyst is a compound of formula IV, wherein:

R5 and R6 are the same or different and are each C 6 -C 10 -aryl, mono- or poly-C 1 -C 4 -alkyl-substituted C 6 -C 10 -aryl, optionally mono- or poly-C 1 -C 4 -alkyl-substituted C 1 -C 10 -alkyl or C 3 -C 6 -cycloalkyl,

R7 and R8 are the same or different and are each a branched or unbranched C 1 -C 6 -alkyl, and

with the proviso that, when R7 and R8 are each hydrogen, R5 and R6 are not both phenyl.

7. The process of claim 4 , wherein R and R′ are both H and R″ is CH 3 SCH 2 CH 2 .

8. The process of claim 4 , wherein:

R is H,

R′ a straight-chain or branched and optionally substituted CH 1 C 12 -alkyl radical and

R″ is CH 3 SCH 2 CH 2 .

9. The process of claim 4 , wherein:

R is H,

R′ is CH 3 and

R″ is CH 3 SCH 2 CH 2 .

10. The process of claim 4 , wherein:

R is H,

R′ is C 2 H 5 and

R″ is CH 3 SCH 2 CH 2 .

11. The process of claim 4 , wherein said catalyst is used at a concentration of 0.1-5 mol % based on the aldehyde.

12. The process of claim 11 , wherein said process is performed at a temperature of −20° C. to 100° C.

13. The process of claim 11 , wherein said process is performed at a temperature of 15° C. to 80° C.

14. The process of claim 13 , wherein said process is performed under a partial pressure of 0.1-20 bar of carbon dioxide.

15. A compound of formula VI, formula VII or formula VIII:

16. A process for preparing a catalyst of formula II, III or IV:

wherein:

R 1 and R 2 are the same or different and are each a C 6 -C 10 -aryl, heteroaryl, branched or unbranched, optionally mono- or poly-C 1 -C 4 -alkyl- or -heteroalkyl-substituted C 1 -C 10 -alkyl, C 3 -C 6 -cycloalkyl or mono- or poly-C 1 -C 4 -alkyl-substituted C 6 -C 10 -aryl,

R 3 and R 4 are the same or different and are each hydrogen, branched or unbranched C 1 -C 6 -alkyl, C 3 -C 6 -cycloalkyl, C 6 -C 10 -aryl or heteroaryl;

R5 and R6 are the same or different and are each a poly-C 1 -C 4 -alkyl-substituted C 6 -C 10 -aryl, or poly-C 1 -C 4 -alkyl-substituted C 1 -C 10 -alkyl; and

R7 and R8 are the same or different and are each a branched or unbranched C 1 -C 6 -alkyl;

said process comprising, reacting a compound of formula IX, X or XI:

with CO 2 in the presence of a base,

and wherein X is Cl, Br, I, pCH 3 C 6 H 4 SO 3 , BF 4 , PF 6 , or CH 3 SO 3 .

17. The process of claim 16 , wherein said base has a corresponding acid with a pKa greater than 8.

18. The process of claim 17 , wherein said base is an alkali metal or alkaline earth metal carboxylate, alkali metal or alkaline earth metal alkoxide, alkali metal or alkaline earth metal carbonate or a primary, secondary, or tertiary amine or bicyclic amine.

19. The process of claim 17 , wherein said base is sodium acetate, potassium tert-butoxide, or 1,8-diazabicyclo [5.4.0]undec-7-ene (DBU).

20. The process of claim 16 , wherein said process is performed at temperatures of 15 to 80° C.