Synthesis of fluoro hemiacetals via transition metal-catalyzed fluoro ester and carboxamide hydrogenation

1. A process for producing a fluorinated hemiacetal, said process comprising:

reacting a fluorinated precursor with hydrogen gas in the presence of a transition metal-ligand complex and a base,

wherein said fluorinated precursor is of the general formula (I):

wherein R 1 is an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an arylalkyl group, an alkoxy group, or an aryloxy group;

wherein R 2 is O—R 6 or —N—(R 6 ) 2 ;

wherein at least one of R 1 and R 2 is fluorinated or perfluorinated;

wherein said transition metal-ligand complex is of general formula (II), general formula (III), general formula (IV), or general formula (V):

wherein R 3 is C 1-6 alkyl, C 3-6 cycloalkyl, aryl, heteroaryl, or arylalkyl;

wherein R 4 is H, C 1-6 alkyl, C 3-6 cycloalkyl, aryl, heteroaryl, or arylalkyl;

wherein each R 5 , independently, is an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, an arylalkyl group, an alkoxy group, or an aryloxy group;

wherein Y is —P or —P═O;

wherein M is a transition metal;

wherein m is 1, 2, 3, 4, or 5;

wherein n is 1, 2, 3, 4, or 5;

wherein q is 0, 1, or 2;

wherein each of X 1 and X 2 , independently, is a ligand with a formal charge of −1 or 0;

wherein X 3 is absent or is a ligand with a formal charge of −1 or 0;

wherein each alkyl, cycloalkyl, aryl, heteroaryl, arylalkyl, alkoxy, aryloxy, or aromatic group may be substituted or unsubstituted; and

wherein said fluorinated hemiacetal is of the general formula:

wherein each R 6 , independently, is H, F, an alkyl group, a cycloalkyl group, an aryl group, a heteroaryl group, or an arylalkyl group; and

wherein if the transition metal-ligand complex is of general formula (II), m is 1, n is 1, q is 0, R 3 is methyl, R 4 is H, each R 5 is phenyl, and M is Ru, then Y is P.

2. The process of claim 1 , wherein said transition metal-ligand complex is of general formula (IIa), general formula (IIIa), general formula (IVa), general formula (Va), general formula (IIb), general formula (IIIb), general formula (IVb), or general formula (Vb):

3. The process of claim 1 , wherein R 1 is C 1-6 fluoroalkyl, C 3-6 fluorocycloalkyl, fluoroaryl, fluoroheteroaryl, fluoroarylalkyl, fluoroalkoxy, or fluoroaryloxy.

4. The process of claim 1 , wherein R 6 is C 1-6 fluoroalkyl, C 3-6 fluorocycloalkyl, fluoroaryl, fluoroheteroaryl, or fluoroarylalkyl.

5. The process of claim 1 , wherein each R 6 is, independently, selected from the group consisting of H, F, CF 3 , CHF 2 , CH 2 F, CH 2 CF 3 , CH 2 CHF 2 , CH 2 CH 2 F, CF 2 CH 3 , CF(CH 3 ) 2 , CF 2 CH(OH)C 2 H 5 , CHFCH 2 C(═CH 2 )CH 3 , CF 2 CH═CHCH 3 , CF 2 CH 2 CH═CHCH 3 , CH 2 (CH 2 ) 2 CH═CHCH 3 , CF 2 C 6 H 5 ,

and

6. The process of claim 1 , wherein each of X 1 , X 2 , and X 3 is independently alkyl, aryl, alkoxy, aryloxy, carboxylate, halo, hydrido, hydrogen, hydroxyl, NO, OTf (triflate), OTs (tosylate), phosphate, BH 4 , a nitrile, an amine, carbonyl, an ether, a phosphine, a phosphine oxide, a phosphite, or a sulfoxide.

7. The process of claim 1 , wherein each R 5 , independently, is an aryl group or an arylalkyl group.

8. The process of claim 1 , wherein M is Ru or Ir.

9. The process of claim 8 , wherein the transition metal-ligand complex comprises one of the following structures:

10. The process of claim 1 , wherein the fluorinated precursor is a fluorinated ester.