Main-group metal based asymmetric catalysts and applications thereof

• US 6,521,561 B1
• Filed: 05/01/1998
• Issued: 02/18/2003
• Est. Priority Date: 05/01/1998
• Status: Expired due to Term

• Current Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Original Assignee: President and Fellows of Harvard College (Harvard Corporation)
• Inventors: Jacobsen, Eric N., Sigman, Matthew S.
• Primary Examiner(s): Wood, Elizabeth D.
• Application Number:
  US09/071,842
• Time in Patent Office: 1,754 Days
• Field of Search: 502/163, 502/167, 502/171, 502/168, 502/162
• US Class Current: 502/162
• CPC Class Codes: B01J 2231/341 1,2-additions, e.g. aldol or Knoevenagel condensations
• CPC Class Codes: B01J 2231/348 1,4-additions, e.g. conjugate additions
• CPC Class Codes: B01J 2531/0244 Pincer-type complexes, i.e. consisting of a tridentate skeleton bound to a metal, e.g. by one to three metal-carbon sigma-bonds
• CPC Class Codes: B01J 2531/025 Ligands with a porphyrin ring system or analogues thereof, e.g. phthalocyanines, corroles
• CPC Class Codes: B01J 2531/0252 Salen ligands or analogues, e.g. derived from ethylenediamine and salicylaldehyde
• CPC Class Codes: B01J 2531/31 Aluminium
• CPC Class Codes: B01J 2531/46 Titanium
• CPC Class Codes: B01J 2531/62 Chromium
• CPC Class Codes: B01J 2531/72 Manganese
• CPC Class Codes: B01J 2531/821 Ruthenium
• CPC Class Codes: B01J 2531/845 Cobalt
• CPC Class Codes: B01J 31/183 with more than one complexing nitrogen atom, e.g. phenanthroline
• CPC Class Codes: B01J 31/2243 At least one oxygen and one nitrogen atom present as complexing atoms in an at least bidentate or bridging ligand
• CPC Class Codes: C07B 2200/07 Optical isomers
• CPC Class Codes: C07B 53/00 Asymmetric syntheses
• CPC Class Codes: C07C 227/32 by stereospecific synthesis
• CPC Class Codes: C07C 229/36 with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
• CPC Class Codes: C07C 253/10 to compounds containing carbon-to-carbon double bonds
• CPC Class Codes: C07C 255/29 containing cyano groups and acylated amino groups bound to the carbon skeleton
• CPC Class Codes: C07C 255/31 having cyano groups bound to acyclic carbon atoms of a carbon skeleton containing rings other than six-membered aromatic rings
• CPC Class Codes: C07C 255/44 : at least one of the singly-bound nitrogen atoms being acylated
• CPC Class Codes: C07C 2601/14 : The ring being saturated

Abstract

The present invention relates to a method and catalysts for the stereoselective addition of a nucleophile to a reactive π-bond of a substrate. The chiral, non-racemic catalysts of the present invention constitute the first examples of catalysts for nucleophilic additions that comprise a main-group metal and a tri- or tetra-dentate ligand.

Claims

1. A chiral catalyst represented by the following formula:

the substituents R₁, R₂, Y₁, Y₂, X₁, X₂, X₃ and X₄ each, independently, represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —

(CH₂)_m—

R₇,

or any two or more of the substituents taken together form a carbocyle or heterocycle ring having from 4 to 8 atoms in the ring structure,

with the proviso that at least one of R₁, Y₁, X₁ and X₂ is covalently bonded to at least one of R₂, Y₂, X₃ and X₄ to provide the β

-iminocarbonyls to which they are attached as a tetradentate ligand, and at least one of Y₁ and Y₂ is a hydrogen;

R₇ represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle, or a polycycle;

m is zero or an integer in the range of 1 to 8;

M represents a main-group metal selected from Group 1, 2, 13 or 14 of the periodic table; and

A represents a counterion or a nucleophile,

wherein each of the substituents R₁, R₂, Y₁, Y₂, X₁, X₂, X₃ and X₄, are selected such that the catalyst is asymmetric.

2. The catalyst of claim 1, wherein the main-group metal is selected from Groups 13, or 14.

3. The catalyst of claim 1, wherein M is selected from the group consisting of Li, Na, K, Rb, Cs, Be, Mg,Ca, Sr, Ba, B, Al, Ga, In, Si, Ge, and Sn.

4. The catalyst of claim 1, wherein M is Al(III).

5. The chiral catalyst represented by formula 104:

in which

the B₁ moiety represents a diimine bridging substituent represented by —

R₁₅—

R₁₆—

R₁₇—

, wherein R₁₅ and R₁₇ each independently are absent or represent an alkyl, an alkenyl, or an alkynyl, and R₁₆ is absent or represents an amine, an imine, an amide, a phosphoryl, a carbonyl, a silyl, an oxygen, a sulfur, a sufonyl, a selenium, a carbonyl, or an ester;

each of B₂ and B₃ independently represent rings selected from a group consisting of cycloalkyls, cycloakenyls, aryls, and heterocyclic rings, which rings comprising from 4 to 8 atoms in a ring structure;

Y₁ and Y₂ each independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —

(CH₂)_m—

R₇,

R₁₂, R₁₃, and R₁₄ each independently are absent, or represent one or more covalent substitutions of B₁, B₂ and B₃ with halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —

(CH₂)_m—

R₇, wherein R₁₂ can occur on one or more positions of —

R₁₅—

R₁₆—

R₁₇—

, or any two or more of the R₁₂, R₁₃, R₁₄, Y₁ and Y₂ taken together form a bridging substituent;

R₇ represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle , or a polycycle;

m is zero or an integer in the range of 1 to 8;

M represents a main-group metal selected from Group 1, 2, 13 or 14 of the periodic table; and

A represents a counterion or a nucleophile,

wherein R₁₂, R₁₃, R₁₄, Y₁ and Y₂ are selected such that the catalyst is asymmetric.

6. The catalyst of claim 5, wherein the main-group metal is selected from Groups 13, or 14.

7. The catalyst of claim 5, wherein M is selected from the group consisting of Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba, B, Al, Ga, In, Si, Ge, and Sn.

8. The catalyst of claim 5, wherein M is Al(III).

9. The chiral catalyst represented by formula 106:

in which

each of the substituents R₁, R₂, R₃, R₄, R₅, Y₁, Y₂, X₁, X₂, X₃, X₄, X₅, X₆, X₇, and X₈, independently, represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —

(CH₂)_m—

R₇;

or any two or more of the substituents taken together form a carbocycle or heterocycle having from 4 to 10 atoms in the ring structure;

R₇ represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle;

m is zero or an integer in the range of 1 to 8;

M represents a main-group metal selected from Group 1, 2, 13 or 14 of the periodic table; and

A represents a counterion or a nucleophile;

wherein

if R₅ is absent, at least one of R₁ and R₂ is taken together with at least one of R₃ and R₄ to form a bridging substituent, and each of of the substituents of 106 are selected such that the salenate is asymmetric.

10. The catalyst of claim 9, wherein the main-group metal is selected from Groups 13, or 14.

11. The catalyst of claim 9, wherein M is selected from the group consisting of Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba, B, Al, Ga, In, Si, Ge, and Sn.

12. The catalyst of claim 9, wherein M is Al(III).

13. The chiral catalyst represented by formula 100:

in which

Z₁, Z₂, Z₃ and Z₄ each represent a Lewis base;

the C₁ moiety, taken with Z₁, Z₃ and M, and the C₂ moiety, taken with Z₂, Z₄ and M, each, independently, form a heterocycle;

R₁, R₂, R′

₁ and R′

₂ each, independently, are absent or represent a covalent substitution with an organic or inorganic substituent permitted by valence requirements of the electron donor atom to which it is attached;

R₄₀ and R₄₁ each independently are absent, or represent one or more covalent substitutions of C₁ and C₂ with an organic or inorganic substituent permitted by valence requirements of the ring atom to which it is attached,

or any two or more of the R₁, R₂, R′

₁, R′

₂ R₄₀ and R₄₁ taken together form a bridging substituent;

with the proviso that C₁ is substituted at at least one site by R₁, R′

₁ or R₄₁, and C₂ is substituted at at least one site by R₂, R′

₂ or R₄₀, and

at least one of R₁, R′

₁ and R₄₁ is taken together with at least one of R₂, R′

₂ and R₄₀ to form a bridging substituent so as to provide Z₁, Z₂, Z₃ and Z₄ as a tetradentate ligand;

M represents a main-group metal selected from Group 1, 2, 13 or 14 of the periodic table; and

A represents a counterion or a nucleophile; and

R₁, R₂, R′

₁, R′

₂ R₄₀ and R₄₁ are selected to provide at least one stereogenic center in said tetradentate ligand.

14. The catalyst of claim 13, wherein

R₁, R₂, R′ ₁ and R′

₂, independently, represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —

(CH₂)_m—

R₇;

each R₄₀ and R_{4 1} occuring in 100 independently represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imnines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —

(CH₂)_m—

R₇;

R₇ represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle; and

m is zero or an integer in the range of 1 to 8.

15. The catalyst of claim 13 or 14, wherein each Z₁, Z₂, Z₃ and Z₄ are independently selected from the group comprising nitrogen, oxygen, phosphorus, arsenic, and sulfur.

16. The catalyst of claim 13, wherein the main-group metal is selected from Groups 13, or 14.

17. The catalyst of claim 16, wherein M is selected from the group consisting of Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba, B, Al, Ga, In, Si, Ge, and Sn.

18. The catalyst of claim 17, wherein M is Al(III).

19. A composition comprising an metallosalenate catalyst, which catalyst is represented by the formula:

in which

each of the substituents R₁, R₂, R₃, R₄, R₅, Y₁, Y₂, X₁, X₂, X₃, X₄, X₅, X₆, X₇, and X₈, independently, represent hydrogen, halogens, alkyls, alkenyls, alkynyls, hydroxyl, amino, nitro, thiol, amines, imines, amides, phosphoryls, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, or —

(CH₂)_m—

R₇;

or any two or more of the substituents taken together form a carbocycle or heterocycle having from 4 to 10 atoms in the ring structure;

R₇ represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle;

m is zero or an integer in the range of 1 to 8;

M represents a main-group metal selected from Group 1, 2, 13 or 14 of the periodic table; and

A represents a counterion or nucleophile;

wherein

if R₅ is absent, at least one of R₁ and R₂ is taken together with at least one of R₃ and R₄ to form a bridging substituent, and each of of the substituents of 106 are selected such that the salenate is asymmetric.

20. The catalyst of claim 19, wherein the main-group metal is selected from Groups 13, or 14.

21. The catalyst of claim 19, wherein M is selected from the group consisting of Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba, B, Al, Ga, In, Si, Ge, and Sn.

22. The catalyst of claim 19, wherein M is Al(III).

23. The chiral catalyst represented by formula 150:

wherein

R₁₀₆ represents a hydrogen, halogen, alkyl, alkenyl, alkynyl, hydroxyl, amino, nitro, thiol, amine, imine, amide, phosphonate, phosphine, carbonyl, carboxyl, silyl, ether, thioether, sulfonyl, selenoether, ketone, aldehyde, ester, or —

(CH₂)_m—

R₇;

each of R₁₁₂ and R′

₁₁₂ is absent or represent one or more covalent substitutions of the heterocycle to which it is attached;

R₇ represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle;

the catalyst is asymmetric;

m is zero or an integer in the range of 1 to 8;

M represents a main-group metal selected from Group 1, 2, 13 or 14 of the periodic table; and

A represents a counter ion or nucleophile.

24. The catalyst of claim 23, wherein the main-group metal is selected from Groups 13, or 14.

25. The catalyst of claim 23, wherein M is selected from the group consisting of Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba, B, Al, Ga, In, Si, Ge, and Sn.

26. The catalyst of claim 23, wherein M is Al(III).

27. A chiral catalyst represented by structure 108:

wherein

D₁, D₂, D₃ and D₄ each independently represent a heterocycle selected from the set comprising pyrrole, pyrrolidine, pyridine, piperidine, imidazole, and pyrazine;

R₁₈ represents, independently for each occurrence, a bridging substituent which links adjacent heterocycles;

R₁₉, independently for each occurrence;

is absent or represents one or more substituents of the heterocycle to which it is attached;

said substituents are independently selected from the group comprising halogens, alkyls, alkenyls, alkynyls, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol amines, imines, amides, phosphonates, phosphines, carbonyls, carboxyls, silyls, ethers, thioethers, sulfonyls, selenoethers, ketones, aldehydes, esters, and —

(CH₂)_m—

R₇, or any two or more of the R₁₈ and R₁₉ substituents are covalently linked to form a bridging substitution;

R₇ represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle;

m is zero or an integer in the range of 1 to 8; and

M represents a main-group metal selected from Group 1, 2, 13 or 14 of the periodic table, and

the catalyst is asymmetric.

28. The catalyst of claim 27, wherein the main-group metal is selected from Groups 13, or 14.

29. The catalyst of claim 27, wherein M is selected from the group consisting of Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba, B, Al, Ga, In, Si, Ge, and Sn.

30. The catalyst of claim 27, wherein M is Al(III).

31. The chiral catalyst represented by formula 110:

wherein

R₁₉, R′

₁₉, and R₂₀ represent, independently for each occurrence, hydrogen, halogen, alkyl, alkenyl, alkynyls, hydroxyl, alkoxyl, silyloxy, amino, nitro, thiol amines, imine, amide, phosphonate, phosphine, carbonyl, carboxyl, silyl, ether, thioether, sulfonyl, selenoether, ketone, aldehyde, ester, or —

(CH₂)_m—

R₇;

any two R₁₉ and R′

₁₉ substituents on the same pyrrole taken together can form a fused carbocycle or fused heterocycle having from 4 to 7 atoms in the ring structure;

any two or more of the R₁₉, R′

₁₉ and R₂₀ substituents may be covalently cross-linked to form a bridging substituent;

R₇ represents an aryl, a cycloalkyl, a cycloalkenyl, a heterocycle or a polycycle;

m is zero or an integer in the range of 1 to 8; and

M represents a main-group metal selected from Group 1, 2, 13 or 14 of the periodic table; and

the catalyst is asymmetric.

32. The catalyst of claim 31, wherein the main-group metal is selected from Groups 13, or 14.

33. The catalyst of claim 31, wherein M is selected from the group consisting of Li, Na, K, Rb, Cs, Be, Mg, Ca, Sr, Ba, B, Al, Ga, In, Si, Ge, and Sn.

34. The catalyst of claim 31, wherein M is Al(III).

35. The chiral catalyst comprising:

(a) a main-group metal atom or ion selected from Group 1, 2, 13 or 14 of the periodic table; and

(b) an asymmetric tetradentate ligand;

wherein said catalyst catalyzes at least one asymmetric reaction.