Spiroketal-based C2-symmetric scaffold for asymmetric catalysis

Patent metadata

Field	Value
Publication number	US-10565015-B2
Application number	US-201816134568-A
Country	US
Kind code	B2
Filing date	Sep 18, 2018
Priority date	Sep 18, 2017
Publication date	Feb 18, 2020
Grant date	Feb 18, 2020

Abstract

Provided herein is a compound of formula (I):

wherein each R is independently selected from the group consisting of C 1-8 alkyl, C 1-8 heteroalkyl having 1-4 heteroatoms independently selected from N, O, and S, C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl having 1-4 heteroatoms independently selected from N, O, and S, C 6-10 aryl, and 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from N, O, and S; each X is independently selected from OH, PAr 2 , P(O)Ar 2 , OPAr 2 , C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl having 1-4 heteroatoms independently selected from N, O, and S or each X together form O 2 PNR′ 2 ; Ar is C 6-10 aryl; and each R′ is independently selected from hydrogen and C 1-8 alkyl. Also provided are methods of making and using the compound of formula (I).

First claim

What is claimed:

1. A compound of formula (I):

wherein each R is independently selected from the group consisting of C 1-8 alkyl, C 1-8 heteroalkyl having 1-4 heteroatoms independently selected from N, O, and S, C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl having 1-4 heteroatoms independently selected from N, O, and S, C 6-10 aryl, and 5-10 membered heteroaryl having 1-4 heteroatoms independently selected from N, O, and S;
each X is independently selected from OH, PAr 2 , P(O)Ar 2 , OPAr 2 , C 3-6 cycloalkyl, 3-10 membered heterocycloalkyl having 1-4 heteroatoms independently selected from N, O, and S, C 6-10 aryl, and 5-10 membered heteroaryl having 1-4 heteroatoms selected from N, O, and S, or each X together form O 2 PNR′ 2 ;
Ar is C 6-10 aryl; and
each R′ is independently selected from hydrogen and C 1-8 alkyl.

2. The compound of claim 1 , wherein the compound of formula (I) is formula (IA):

3. The compound of claim 1 , wherein the compound of formula (I) has a formula (IB):

4. The compound of claim 1 , wherein at least one X is OH.

5. The compound of claim 1 , wherein at least one X is PAr 2 .

6. The compound of claim 1 , wherein at least one X is OPAr 2 .

7. The compound of claim 1 , wherein at least one X is P(O)Ar 2 .

8. The compound of claim 5 , wherein Ar comprises phenyl.

9. The compound of claim 1 , wherein both X together form O 2 PNR′ 2 .

10. The compound of claim 9 , wherein R′ is methyl.

11. The compound of claim 1 , wherein R is ethyl.

12. The compound of claim 1 , wherein at least one R is 3-10 membered heterocycloalkyl having 1-4 heteroatoms independently selected from N, O, and S.

13. The compound of claim 1 having a structure selected from the group consisting of:

14. A catalyst comprising the compound of formula (I) according to claim 1 and a transition metal.

15. The catalyst of claim 14 , wherein the transition metal comprises iridium, palladium, rhodium, platinum, copper, nickel, cobalt, or gold.

16. A method of preparing the catalyst of claim 14 comprising admixing the compound of formula (I) and the transition metal to form the catalyst.

17. The method of claim 16 , wherein the transition metal comprises [Ir(COD)Cl] 2 , [Pd(allyl)Cl] 2 , or Pd(dba) 2 .

18. The method of claim 16 , wherein the compound of formula (I) and the transition metal are provided in a molar ratio of about 6:1 to 1:1.

19. A method comprising:
admixing a first reactant, a second reactant, and the catalyst of claim 14 under conditions sufficient to allow reaction of the first reactant and the second reactant to form a reaction product, wherein the reaction product comprises a chiral center and the reaction produces an enantiomeric excess (ee) of the reaction product.

20. The method of claim 19 , wherein the reaction comprises a hydroarylation of an asymmetric alkene, an asymmetric Heck reaction, an asymmetric hydrogenation, or an allylic alcohol substitution.

21. A method of preparing compound (S,S,S)-4

comprising
(a) cooling a solution of compound (S)-2 to 0° C.;

wherein PG is a hydroxy protecting group;
(b) adding an organolithium reagent to the cooled solution of step (a) to form a mixture;
(c) warming the mixture of step (b) to room temperature and keeping at room temperature to dissolve suspended material and form a solution;
(d) cooling the solution of step (c) to 0° C.;
(e) admixing the solution of step (d) and diethyl carbonate at 0° C.;
(f) warming the reaction mixture of step (e) to room temperature; and
(g) admixing the reaction mixture of step (f) with acetic acid.

22. A method of preparing compound (S,S,S)-8:

comprising:
admixing diphenylphosphine oxide with compound (S,S,S)-7 and, optionally, in the presence of compound (S,R,S)-7, in the presence of a catalyst to form compound (S,S,S)-8

wherein the temperature of the admixing is 70° C. to 90° C.

23. A method of preparing compound (R,S,S)-8:

comprising:
admixing diphenylphosphine oxide with compound (R,S,S)-7 in the presence of a catalyst to form compound (R,S,S)-8:

wherein the temperature of the admixing is 90° C. to 110° C.

24. The compound of claim 1 , wherein at least one X comprises 4-phenyl-4,5-dihydrooxazole.

Assignees

• Univ Michigan Regents

Inventors

• Nagorny Pavel
• Sun Siyuan
• Arguelles Alonso

Classifications

• G06F9/485

  Task life-cycle, e.g. stopping, restarting, resuming execution (G06F9/4881 takes precedence) · CPC title

• B01J2531/0241

  Rigid ligands, e.g. extended sp2-carbon frameworks or geminal di- or trisubstitution · CPC title

• C07C2603/86

  containing four rings · CPC title

• B01J31/2452

  with more than one complexing phosphine-P atom · CPC title

• B01J2531/824

  Palladium · CPC title