Asymmetric electrophilic fluorination using an anionic chiral phase-transfer catalyst

Patent metadata

Field	Value
Publication number	US-9981977-B2
Application number	US-201214368105-A
Country	US
Kind code	B2
Filing date	Dec 26, 2012
Priority date	Dec 22, 2011
Publication date	May 29, 2018
Grant date	May 29, 2018

Abstract

The discovery of distinct modes of asymmetric catalysis has the potential to rapidly advance chemists' ability to build enantioenriched molecules. As an example, the use of chiral cation salts as phase-transfer catalysts for anionic reagents has enabled a vast set of enantioselective transformations. A largely overlooked analogous mechanism wherein a chiral anionic catalyst brings a cationic species into solution is itself a powerful method. The concept is broadly applicable to a number of different reaction pathways, including to the enantioselective fluorocyclization of olefins, and dearomatization of aromatic systems with a cationic electrophile-transferring (e.g., fluorinating) agent and a chiral phosphate catalyst. The reactions proceed in high yield and stereoselectivity. The compounds and methods of the invention are of particular value, especially considering the scarcity of alternative approaches.

First claim

What is claimed is:

1. A method of cyclizing an alkene, said method comprising:
contacting an alkene having the formula:

wherein
b is selected from 1 and 2;
R 1 , R 2 and R 3 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroraryl, and
a member selected from R 1 and R 2 , R 2 and R 3 , and R 1 , R 2 and R 3 , together with the atoms to which they are attached are optionally joined to fowl a ring system; and
R 4 is a member selected from substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl,

with an ion pair having the formula:
[A] n+ [B] n− ,

wherein n is 1
and A is

B is a chiral anion having the formula:

wherein
R 10 , R 10a , R 11 , R 11a , R 12 , R 12a , R 13 , R 13a are independently members selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, halogen, CN, CF 3 , acyl, —SO 2 NR 8 R 9 , —NR 8 R 9 , —OR 8 , —S(O) 2 R 8 , —C(O)R 9 , —COOR 8 , —CONR 8 R 9 , —S(O) 2 OR 8 , —OC(O)R 8 , —C(O)NR 8 R 9 , —NR 8 C(O)R 9 , —NR 8 SO 2 R 9 and —NO 2 , wherein two or more of R 10 , R 10a , R 11 , R 11a , R 12 , R 12a , R 13 , R 13a , together with the atoms to which they are bonded, are optionally joined to form a ring system which is a member selected from substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl

wherein
R 8 and R 9 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocycloalkyl, and R 8 and R 9 , together with the atoms to which they are bonded, are optionally joined to form a 5- to 7-membered ring under conditions appropriate to cyclize said alkene.

2. The method according to claim 1 , wherein said cyclization of said alkene yields a product having the formula:

wherein
R 5 and R 6 , together with the atoms to which they are attached, are joined to form a ring system which is a member selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted cycloalkyl, and substituted or unsubstituted heterocycloalkyl, wherein said ring system is substituted with at least one member selected from halogen and substituted or unsubstituted aryl; and
R 7 and R 8 are members independently selected from H, substituted or unsubstituted alkyl and substituted or unsubstituted heteroalkyl.

3. The method according to claim 2 , wherein R 5 and R 6 are joined to form a ring system having the formula:

wherein
J is a member selected from halogen and substituted or unsubstituted aryl;
G is a member selected from O and S; and
each R 9 is a member independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl and substituted or unsubstituted heteroaryl, and two or more R 9 moieties, together with the atoms to which they are attached, are optionally joined to form a ring system.

4. The method according to claim 3 , wherein R 5 and R 6 are joined to form a ring system having the formula:

wherein
each R 20 is a member independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, halogen, CN, CF 3 , acyl, —SO 2 NR 18 R 19 , —NR 18 R 19 , —OR 18 , —S(O) 2 R 18 , —C(O)R 18 , —COOR 18 , —CONR 18 R 19 , —S(O) 2 OR 18 , —OC(O)R 18 , —C(O)NR 18 R 19 , —NR 18 C(O)R 19 , —NR 18 SO 2 R 19 and —NO 2 ,
wherein
R 18 and R 19 are members independently selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl and substituted or unsubstituted heterocycloalkyl, and R 18 and R 19 , together with the atoms to which they are bonded, are optionally joined to form a 5- to 7-membered ring.

5. The method according to claim 3 , wherein G is O.

6. The method according to claim 3 , wherein J is F.

7. The method according to claim 3 , wherein each R 9 is H.

8. The method according to claim 1 , wherein said product is produced with an ee of at least about 80% enantiomeric excess.

Assignees

• Univ California

Inventors

• Rauniyar Vivek
• Lackner Aaron D
• Hamilton Gregory L
• Toste F Dean
• Phipps Robert J
• Shunatona Hunter
• Frueh Natalja
• Wang Yiming
• Wu Jeffrey
• Patel Jigar
• Honjo Takashi

Classifications

• C07C2601/04

  with a four-membered ring · CPC title

• C07C2602/10

  the other ring being six-membered, e.g. tetraline · CPC title

• C07C2602/24

  the ring system containing nine carbon atoms, e.g. perhydroindane · CPC title

• C07C2602/28

  Hydrogenated naphthalenes · CPC title

• C07C2603/72

  Ethanonaphthalenes; Hydrogenated ethanonaphthalenes · CPC title