Environmentally-friendly hydroazidation of olefins

1. A process for preparing an organic azide of Formula III comprising mixing an olefin of Formula I, a silylazide of Formula II, a hydrogen bond donor, and an organic promoter:

wherein:

R 1 and R 2 are independently selected from hydrogen, alkyl, cycloalkyl, heteroalkyl, and heterocycloalkyl, wherein each of R 1 and R 2 that is not hydrogen is optionally substituted with one or more substituents selected from oxo, halo, cyano, azido, nitro, R 7 , —OR 7 , —N(R 7 )(R 7 ), —(C═O)R 7 , —(C═O)OR 7 , —(C═O)N(R 7 )(R 7 ), —O(C═O)R 7 , —N(R 7 )(C═O)R 7 , —O(C═O)N(R 7 )(R 7 ), and —N(R 7 )(C═O)OR 7 ;

wherein at least one of R 1 and R 2 is not hydrogen;

R 3 is selected from hydrogen, alkyl, cycloalkyl, heteroalkyl, and heterocycloalkyl, wherein R 3 other than hydrogen is optionally substituted with one or more substituents selected from oxo, halo, cyano, azido, nitro, R 7 , —OR 7 , —N(R 7 )(R 7 ), —(C═O)R 7 , —(C═O)OR 7 , —(C═O)N(R 7 )(R 7 ), —O(C═O)R 7 , —N(R 7 )(C═O)R 7 , —O(C═O)N(R 7 )(R 7 ), and —N(R 7 )(C═O)OR 7 ; or

R 1 and R 2 or R 2 and R 3 are taken together with the carbons to which they are attached to form a cycloalkyl ring or an heterocycloalkyl ring, wherein each cycloalkyl or heterocycloalkyl ring is optionally substituted with one or more substituents selected from oxo, halo, cyano, azido, nitro, R 7 , —OR 7 , —N(R 7 )(R 7 ), —(C═O)R 7 , —(C═O)OR 7 , —(C═O)N(R 7 )(R 7 ), —O(C═O)R 7 , —N(R 7 )(C═O)R 7 , —O(C═O)N(R 7 )(R 7 ), and —N(R 7 )(C═O)OR 7 ;

R 4 is independently selected at each occurrence from alkyl and cycloalkyl;

the organic promoter is selected from:

R 5 is independently selected from hydrogen, halo, cyano, azido, nitro, R 7 , —OR', —N(R 7 )(R 7 ), —(C═O)R 7 , —(C═O)OR 7 , —(C═O)N(R 7 )(R 7 ), —O(C═O)R 7 , —N(R 7 )(C═O)R 7 , —O(C═O)N(R 7 )(R 7 ), and —N(R 7 )(C═O)OR 7 ;

m is 1, 2, 3, or 4;

Z is I;

R 6 and R 6′ are independently selected from —O(C═O)R 7 , —O(SO 2 )(R 7 ), hydroxyl, and azido;

R 7 is independently selected at each occurrence from hydrogen, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, and trialkylsilyl, each of which R 7 other than hydrogen is optionally substituted with one or more substituents selected from alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, and haloalkoxy; or

two R 7 groups may be brought together with the atoms to which they are attached to form a cycloalkyl, heterocycloalkyl, aryl, or heteroaryl ring, each of which ring is optionally substituted with one or more substituents selected from alkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, alkoxy, aryloxy, amino, alkylamino, dialkylamino, hydroxyl, halo, acylamino, aminoacyl, cyano, nitro, azido, acyl, acyloxy, carboxyl, carboxyl ester, alkanoyl, carboxamide, haloalkyl, and haloalkoxy;

R 8 and R 8′ are independently selected from hydrogen, halo, cyano, azido, nitro, R 7 , —OR 7 , —N(R 7 )(R 7 ), —(C═O)R 7 , —(C═O)OR 7 , —(C═O)N(R 7 )(R 7 ), —O(C═O)R 7 , —N(R 7 )(C═O)R 7 , —O(C═O)N(R 7 )(R 7 ), and —N(R 7 )(C═O)OR 7 ; or

R 8 and R 8′ may be brought together with the carbon to which they are attached to form a cycloalkyl or heterocycloalkyl ring, each of which ring is optionally substituted with one or more substituents selected from oxo, halo, cyano, azido, nitro, R 7 , —OR', —N(R 7 )(R 7 ), —(C═O)R 7 , —(C═O)OR 7 , —(C═O)N(R 7 )(R 7 ), —O(C═O)R 7 , —N(R 7 )(C═O)R 7 , —O(C═O)N(R 7 )(R 7 ), and —N(R 7 )(C═O)OR 7 ; or

R 8 and R 8′ are brought together to form an oxo or imino group;

R 9 is aryl or heteroaryl, wherein R 9 is optionally substituted with one or more substituents selected from oxo, halo, cyano, azido, nitro, R 7 , —OR', —N(R 7 )(R 7 ), —(C═O)R 7 , —(C═O)OR 7 , —(C═O)N(R 7 )(R 7 ), —O(C═O)R 7 , —N(R 7 )(C═O)R 7 , —O(C═O)N(R 7 )(R 7 ), and —N(R 7 )(C═O)OR 7 ; and

the hydrogen bond donor is water and optionally a second hydrogen bond donor.

2. The process of claim 1 , wherein the olefin of Formula I is selected from

3. The process of claim 1 , wherein the olefin of Formula I is selected from

4. The process of claim 1 , wherein the hydrogen bond donor is water.

5. The process of claim 1 , wherein the hydrogen bond donor is water and a second hydrogen bond donor selected from formic acid, an alkylcarboxylic acid, a (cycloalkyl)carboxylic acid, a (heteroalkyl)carboxylic acid, a (heterocycloalkyl)carboxylic acid, an arylcarboxylic acid, an (heteroaryl)carboxylic acid, sulfuric acid, an alkylsulfonic acid, a (cycloalkyl)sulfonic acid, a (heteroalkyl)sulfonic acid, a (heterocycloalkyl)sulfonic acid, a arylsulfonic acid, and a (heteroaryl)sulfonic acid.

6. The process of claim 5 , wherein the hydrogen bond donor is water and trifluoroacetic acid.

7. The process of claim 1 , wherein the organic promoter is

8. The process of claim 7 , wherein the organic promoter is selected from

9. The process of claim 1 , wherein the organic promoter is

10. The process of claim 9 , wherein the organic promoter is selected from

wherein o is 1, 2, 3, 4, or 5.

11. The process of claim 8 , wherein R 7 is trifluoromethyl or trichloromethyl.

12. The process of claim 1 , wherein R 4 is alkyl.

13. The process of claim 1 , wherein the silylazide of Formula II is trimethylsilylazide or triethylsilylazide.