Bicyclic methylene aziridines and reactions thereof

Patent metadata

Field	Value
Publication number	US-9783512-B2
Application number	US-201514940586-A
Country	US
Kind code	B2
Filing date	Nov 13, 2015
Priority date	Aug 29, 2011
Publication date	Oct 10, 2017
Grant date	Oct 10, 2017

Abstract

The oxidative functionalization of olefins is a common method for the formation of vicinal carbon-heteroatom bonds. However, oxidative methods to transform allenes into synthetic motifs containing three contiguous carbon-heteroatom bonds are much less developed. The use of bicyclic methylene aziridines (MAs), prepared via intramolecular allene aziridination, as scaffolds for functionalization of all three allene carbons, among other reactions, is described herein.

First claim

What is claimed is:

1. A method of forming a bicyclic methylene aziridine by an intramolecular allene aziridination reaction, the method comprising:
combining an allene, an effective rhodium catalyst, a solvent, and an oxidant, to provide a reaction mixture, thereby initiating an intramolecular allene aziridination reaction, to provide a bicyclic methylene aziridine having a structure as shown in Formula II:

wherein
R 1 and R 2 are each independently H, alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, (alkyl)cycloalkyl, (alkyl)aryl, (alkyl)heteroaryl, or (alkyl)heterocycle;
n is 0, 1, or 2;
Y is —C(═O)— or —S(═O) 2 —; and
each Z is independently —(CH 2 )—, —(CHR 1 ), or —(C(R 1 ) 2 )—; and

wherein the allene comprises an allene group tethered to an amino group (—NH 2 ), and the amino group is separated from the nearest carbon atom of the allene group by 3, 4, 5, or 6 atoms linearly.

2. The method of claim 1 , wherein the rhodium catalyst is Rh 2 (esp) 2 where esp is α,α,α′,α′-tetramethyl-1,3-benzenedipropionate, or Rh 2 (TPA) 4 where TPA is triphenylacetate.

3. The method of claim 2 , wherein the oxidant is a hypervalent iodide oxidant or a one-electron cerium or lead oxidant.

4. The method of claim 3 , wherein the oxidant is PhIO, PhI(OAc) 2 , PhI(OPiv) 2 , Ce 2 (SO 4 ) 3 , or Pb(OAc) 4 .

5. The method claim 4 , wherein the reaction mixture further comprises a drying agent, an acid neutralizing agent, or a combination thereof.

6. The method of claim 1 , wherein the aziridine nitrogen of the bicyclic methylene aziridine is substituted by an electron-withdrawing group.

7. The method of claim 1 , wherein the allene is mono-substituted, di-substituted, tri-substituted, or tetra-substituted.

8. The method of claim 1 , wherein the allene is a compound of Formula I:

wherein
R 1 , R 2 , and R 3 are each independently H, alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, (alkyl)cycloalkyl, (alkyl)aryl, (alkyl)heteroaryl, or (alkyl)heterocycle;
n is 1, 2, or 3;
Y is —C(═O)— or —S(═O) 2 —; and
each Z is independently —(CH 2 )—, —(CHR 1 ), or —(C(R 1 ) 2 )—.

9. The method of claim 8 , further comprising contacting the bicyclic methylene aziridine with a nucleophile to provide a nucleophile-addition product.

10. The method of claim 9 , wherein the nucleophile-addition product is an enecarbamate or an enesulphone.

11. The method of claim 9 , wherein the nucleophile comprises a carboxylic acid, a halide, an alcohol in the presence of an acid, a thiol in the presence of an acid, a cyanide, an azide, a malonate, or an alkyl magnesium nucleophile.

12. The method of claim 9 , wherein the nucleophile-addition product is a compound of Formula III:

wherein
R 1 and R 2 are each independently H, alkyl, cycloalkyl, aryl, heteroaryl, heterocycle, (alkyl)cycloalkyl, (alkyl)aryl, (alkyl)heteroaryl, (alkyl)heterocycle, or azide;
n is 0 or 1;
the dotted lines represent optional double bonds where only one of the double bonds is present;
Y is —C(═O)— or —S(═O) 2 —; and
R N is acetoxy, chloroacetoxy, halo, cyano, hydroxyl, alkoxy, thioalkyl, or thioaryl.

13. The method of claim 12 , further comprising reacting the nucleophile-addition product with an electrophile to provide an electrophile-addition product.

14. The method of claim 13 , further comprising reducing the electrophile-addition product to provide a synthetic motif containing three contiguous carbon-heteroatom bonds.

15. The method of claim 12 , further comprising contacting the nucleophile-addition product with a nitrene equivalent in the presence of an oxidant to provide an N,N-spiroaminal.

16. The method of claim 15 , wherein the N,N-spiroaminal has four contiguous carbon-heteroatom bonds in the form of a tricyclic 1,4-diazaspiro[2.2]pentane (DASP).

17. The method of claim 16 , further comprising contacting the DASP and a nucleophile to provide a bicyclic ring opened nucleophile-addition product.

Assignees

• Wisconsin Alumni Res Found
• Wisconsin Alumi Res Found

Inventors

• Schomaker Jennifer
• Boralsky Luke
• Hershberger John
• Rigoli Jared
• Adams Christopher S

Classifications

• C07D291/06

  Six-membered rings · CPC title

• C07D498/10

  Spiro-condensed systems · CPC title

• C07D267/06 Primary

  having the hetero atoms in positions 1 and 3 · CPC title

• C07D263/22

  with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, directly attached to other ring carbon atoms · CPC title

• C07D498/20

  Spiro-condensed systems · CPC title