Highly Z-selective olefin metathesis

1. A method comprising:

providing a catalyst having the structure:

wherein M is Mo or W;

R 1 is aryl, heteroaryl, alkyl, heteroalkyl, optionally substituted;

R 2 and R 3 can be the same or different and are hydrogen, alkyl, alkenyl, heteroalkyl, heteroalkenyl, aryl, or heteroaryl, optionally substituted; and

R 4 and R 5 can be the same or different and are alkyl, heteroalkyl, aryl, heteroaryl, silylalkyl, or silyloxy, optionally substituted, wherein at least one of R 4 or R 5 is a ligand containing oxygen bound to M; and

reacting a first molecule comprising a terminal double bond with a second molecule that comprises a terminal double bond in the presence of the catalyst to produce a product comprising an internal double bond, and

wherein the internal double bond of the product comprises one carbon atom from the terminal bond of the first molecule and one carbon atom from the terminal double bond of the second molecule.

2. The method of claim 1 , wherein the first molecule and the second molecule are identical.

3. The method of claim 1 , wherein at least about 30% of the internal double bond of the product is formed as the Z-isomer.

4. The method of claim 1 , wherein the reaction proceeds with a conversion of at least about 30%.

5. The method of claim 1 , wherein at least one of the first and second molecules has the formula:

wherein R a is H, alkyl, alkenyl, heteroalkyl, heteroalkenyl, aryl, heteroaryl, or acyl, optionally substituted.

6. The method of claim 1 , wherein one of R 4 and R 5 is a ligand containing oxygen bound to M, optionally substituted, and the other is a ligand containing nitrogen bound to M, optionally substituted.

7. The method of claim 6 , wherein the at least one ligand containing oxygen bound to M lacks a plane of symmetry.

8. The method of claim 6 , wherein the ligand containing nitrogen bound to M is selected from the group consisting of pyrrolyl, pyrazolyl, pyridinyl, pyrazinyl, pyrimidinyl, imidazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, thiazolyl, isothiazolyl, indolyl, indazolyl, carbazolyl, morpholinyl, piperidinyl, and oxazinyl, all optionally substituted.

9. The method of claim 6 , wherein the ligand containing oxygen bound to M comprises a group having the formula —OSi(R 22 ) 3 , wherein each R 22 can be the same or different and is aryl or alkyl, optionally substituted.

10. The method of claim 6 , wherein the ligand containing nitrogen bound to M has the structure:

wherein each R 6 can be the same or different and is hydrogen, alkyl, heteroalkyl, aryl, or heteroaryl, optionally substituted; and

X may be present or absent and is any non-interfering group.

11. The method of claim 6 , wherein the ligand containing oxygen bound to M has the following structure:

wherein R 7 is aryl, heteroaryl, alkyl, or heteroalkyl, optionally substituted;

R 8 is

hydrogen, —OH, halogen, alkyl, heteroalkyl, aryl, heteroaryl, acyl, acyloxy, or —OP, optionally substituted; or,

together R 7 and R 8 are joined to form a ring, optionally substituted;

R 9 is

when R 8 is not

or —OH, —OP, or amino, optionally substituted;

R 10 is hydrogen, halogen, alkyl, heteroalkyl, aryl, heteroaryl, or acyl, optionally substituted;

each R 11 , R 12 , R 13 , and R 14 can be the same or different and is aryl, heteroaryl, alkyl, heteroalkyl, or acyl, optionally substituted; or,

together R 11 and R 12 are joined to form a ring, optionally substituted; or

together R 13 and R 14 are joined to form a ring, optionally substituted; and

P is a protecting group.

12. The method of claim 6 , wherein R 4 is a derivative of the following structure:

wherein P is a silyl protecting group.

13. The method of claim 1 , wherein R 1 is:

wherein each R 17 can be the same or different and is hydrogen, halogen, alkyl, heteroalkyl, aryl, acyl, or —OP, optionally substituted; and

P is a protecting group.

14. The method of claim 1 , wherein R 1 is:

wherein each R 17 can be the same or different and is hydrogen, halogen, alkyl, heteroalkyl, aryl, acyl, or —OP, optionally substituted; and

P is a protecting group.

15. The method of claim 1 , wherein R 1 is

wherein each R 17 can be the same or different and is hydrogen, halogen, alkyl, heteroalkyl, aryl, acyl, or —OP, optionally substituted;

R 2 is CMe 2 Ph or CMe 3 ;

R 3 is H; and

R 4 is an enantiomer of the following structure,

wherein each R 7 and R 10 is the same or different and is halogen, methyl, t-butyl, CF 3 , or aryl, optionally substituted; and

P is a protecting group.

16. The method of claim 15 , wherein R 5 has the following structure:

wherein each R 6 can be the same or different and is hydrogen, alkyl, heteroalkyl, aryl, heteroaryl, optionally substituted; and

X may be present or absent and is any non-interfering group.

17. The method of claim 6 , wherein the ligand containing oxygen or nitrogen bound to M has the following structure:

wherein each R 7 and R 8 can be the same or different and is hydrogen, halogen, alkyl, alkoxy, aryl, acyl, or a protecting group, optionally substituted;

R 10 is hydrogen, halogen, alkyl, heteroalkyl, aryl, heteroaryl, or acyl, optionally substituted;

each R 11 , R 12 , R 13 , and R 14 can be the same or different and is aryl, heteroaryl, alkyl, heteroalkyl, or acyl, optionally substituted; or,

together R 11 and R 12 are joined to form a ring, optionally substituted; or,

together R 13 and R 14 are joined to form a ring, optionally substituted;

R 15 is alkyl, aryl, or a protection group, optionally substituted;

R 16 is hydrogen or an amine protecting group;

X can be any non-interfering group;

each Z can be the same or different and is (CH 2 ) m , N, O, optionally substituted;

n is 0-5; and

m is 1-4.

18. The method of claim 1 , wherein the catalyst has a structure selected from the group consisting of M(NAr)(Pyr)(CHR 2 )(OHIPT), M(NAr)(Pyr)(C 3 H 6 )(OHIPT), M(NAr)(CHCMe 2 Ph)(Pyr)(BiphenTMS), M(NAr)(CHCMe 2 Ph)(Me 2 Pyr)(Br 2 Bitet), M(NAr)(CHCMe 2 Ph)(Me 2 Pyr)(MesBitet), W(NAr)(CHCMe 2 Ph)(Me 2 Pyr)(OPhPh 4 ), M(NAr)(CHCMe 2 Ph)(Pyr)((Trip) 2 BitetTMS), M(NAr Cl )(CHCMe 3 )(Pyr)(BiphenTMS), M(NAr Cl )(CHCMe 3 )(Me 2 Pyr)(OSi(TMS) 3 ), M(NAr Cl )(CHCMe 3 )(Me 2 Pyr)(OPhPh 4 ), M(NAr Cl )(CHCMe 3 )(Me 2 Pyr)(HIPTO), M(NAr Cl )(CHCMe 3 )(Me 2 Pyr)(HIPTO), M(NAr Cl )(CHCMe 3 )(Me 2 Pyr)(Br 2 Bitet), M(NAr Cl )(CHCMe 3 )(Me 2 Pyr)(MesBitet), M(NAr Cl )(CHCMe 3 )(Pyr)(Mes 2 Bitet), M(NAd)(Me 2 Pyr)(CHR 2 )(Br 2 Bitet), M(NAr′)(Pyr)(CHR 2 )(Mes 2 BitetOMe), M(NAd)(CHCMe 2 Ph)(Me 2 Pyr)(OSi(TMS) 3 ), M(NAd)(CHCMe 2 Ph))(Me 2 Pyr)(HIPTO), M(NAd)(CHCMe 2 Ph)(Me 2 Pyr)(MesBitet), M(NAr)(Pyr)(CHR 2 )(OHIPT), M(NAr′)(CHCMe 2 Ph)(Me 2 Pyr)(OSi(TMS) 3 ), M(NAr′)(CHCMe 2 Ph)(Me 2 Pyr)(OPhPh 4 ), M(NAr)(CHCMe 2 Ph)(Me 2 Pyr)(HIPTO), M(NAr′)(CHCMe 2 Ph)(Me 2 Pyr)(Br 2 Bitet), M(NAr′)(CHCMe 2 Ph)(Pyr)(MesBitet), M(NAr′)(CHCMe 2 Ph)(Me 2 Pyr)(MesBitet), M(NAr′)(CHCMe 2 Ph)(Pyr)(Mes 2 BitetOMe), or M(NAr′)(CHCMe 2 Ph)(Pyr)(Mes 2 Bitet), wherein M is Mo or W, Ar is 2,6-diisopropylphenyl, Ar Cl is 2,6-dichlorophenyl, Ar′ is 2,6-dimethyphenyl, Ad is 1-admantyl, Mes is mesityl, Me 2 Pyr is 2,5-dimethylpyrrolide, Pyr is pyrrolide, TBS is dimethyl-t-butylsilyl, Ts is tosyl, OTf is triflate, Trip is 2,4,6-triisopropylphenyl, HIPTO is hexaisopropylterphenolate, OSi(TMS) 3 is 1,1,1,3,3,3-hexamethyl-2-(trimethylsilyl)trisilan-2-olate, Biphen is 3,3′-di-tert-butyl-5,5′,6,6′-tetramethylbiphenyl-2,2′-diol, BiphenTMS is 3,3′-di-tert-butyl-5,5′,6,6′-tetramethyl-2′-(trimethylsilyloxy)biphenyl-2-olate, Bitet is 5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2,2′-diol, Trip 2 Bitet is 3,3′-bis(2,4,6-triisopropylphenyl)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2,2′-diol, Trip 2 BitetTMS is 3,3′-bis(2,4,6-triisopropylphenyl)-2′-(trimethylsilyloxy)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2-olate, Br 2 Bitet is 3,3′-dibromo-2′-(tert-butyldimethylsilyloxy)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2-olate, MesBitet is 2′-(tert-butyldimethylsilyloxy)-3-mesityl-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2-olate, Mes 2 Bitet is 3,3′-dimesityl-2′-(tert-butyldimethylsilyloxy)-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2-olate, and Mes 2 BitetOMe is 3,3′-dimesityl-2′-methoxy-5,5′,6,6′,7,7′,8,8′-octahydro-1,1′-binaphthyl-2-olate.

19. A method comprising:

providing a catalyst having the structure:

wherein M is Mo or W;

R 1 is aryl, heteroaryl, alkyl, heteroalkyl, optionally substituted;

R 2 and R 3 can be the same or different and are hydrogen, alkyl, alkenyl, heteroalkyl, heteroalkenyl, aryl, or heteroaryl, optionally substituted; and

R 4 and R 5 can be the same or different and are alkyl, heteroalkyl, aryl, heteroaryl, silylalkyl, or silyloxy, optionally substituted, wherein one of R 4 and R 5 is a ligand containing oxygen bound to M, optionally substituted, and the other is a ligand containing nitrogen bound to M, optionally substituted; and

reacting a first molecule comprising a terminal double bond with a second molecule that comprises a terminal double bond in the presence of the catalyst to produce a product comprising an internal double bond, and

wherein the internal double bond of the product comprises one carbon atom from the terminal bond of the first molecule and one carbon atom from the terminal double bond of the second molecule.

20. The method of claim 19 , wherein at least about 30% of the internal double bond of the product is formed as the Z-isomer.