[3+2] annulation to produce 5-membered heterocyclic compounds

Patent metadata

Field	Value
Publication number	US-10358438-B2
Application number	US-201515329615-A
Country	US
Kind code	B2
Filing date	Jul 20, 2015
Priority date	Jul 21, 2014
Publication date	Jul 23, 2019
Grant date	Jul 23, 2019

Abstract

The present invention relates to various organic reactions including a method for producing heterocyclic compounds using a [3+2] annulation; a method for producing fluorinated heteroaromatic compounds; and a method for alkylating a meta-position of a phenolic compound.

First claim

What is claimed is:

1. A method for producing a diastereomerically enriched 3-pyrroline compound of the formula:

said method comprising:
deprotonating an α,β-unsaturated compound of the formula:

with a base under condition sufficient to produce a deprotonated intermediate; and
reacting said deprotonated intermediate with an enantiomerically enriched imine compound of the formula:

under conditions sufficient to produce said diastereomerically enriched 3-pyrroline compound of Formula I,

wherein
R is hydrogen, alkyl, haloalkyl, aryl, aralkyl, alkenyl, aralkenyl, cycloalkyl, heteroalkyl, heteroaryl or ester functional group;
X is a leaving group;
Y is a chiral auxiliary group of the formula —S*(═O)R a , wherein * denotes a chiral center and R a is alkyl, cycloalkyl, aralkyl, alkenyl, aralkenyl, heteroalkyl, or heteroaryl; and
Z is an electron withdrawing conjugated group.

2. The method of claim 1 , wherein said imine compound of Formula III has enantiomeric excess (e.e.) of at least 90% e.e.

3. The method of claim 2 , wherein the diastereomeric excess (d.e.) of said 3-pyrroline compound is at least 90% d.e.

4. The method of claim 3 , wherein the diastereomeric excess (d.e.) of said 3-pyrroline compound is at least 95% d.e.

5. The method of claim 1 , wherein R a is alkyl.

6. The method of claim 5 , wherein R a is tert-butyl.

7. The method of claim 1 , wherein * is an (S)-isomer.

8. The method of claim 1 , wherein * is an (R)-isomer.

9. The method of claim 2 , wherein said imine compound of Formula III has enantiomeric excess of at least 95% e.e.

10. The method of claim 2 , wherein said imine compound of Formula III has enantiomeric excess of at least 99% e.e.

11. The method of claim 3 , wherein the diastereomeric excess of said 3-pyrroline compound is at least 99% d.e.

12. The method of claim 1 further comprising the steps of removing the chiral auxiliary group from said 3-pyrroline compound of Formula I to produce a free 3-pyrroline compound of Formula IA:

wherein
R and Z are those defined in claim 1 .

Assignees

• Univ Arizona

Inventors

• Njardarson Jon T
• Chogii Isaac
• Smith David Townsend
• Vitaku Edon

Classifications

• C07D207/277

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals · CPC title

• C07D405/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title

• C07D207/48

  Sulfur atoms · CPC title

• C07D209/12

  Radicals substituted by oxygen atoms · CPC title

• C07D207/18

  having one double bond between ring members or between a ring member and a non-ring member · CPC title