Novel annulation catalysts via direct c-h bond amination

Patent metadata

Field	Value
Publication number	US-2022016613-A1
Application number	US-201917276855-A
Country	US
Kind code	A1
Filing date	Sep 19, 2019
Priority date	Sep 19, 2018
Publication date	Jan 20, 2022
Grant date	—

Abstract

Disclosed are compounds, methods, reagents, systems, and kits for the preparation and utilization of monomeric or polymeric metal-based compounds. These metal-based compounds are organometallic catalysts composed of substituted dipyrrin ligands bound to transition metals. C—H bond functionalization catalysis can be performed with the disclosed organometallic catalysts to yield C—N bonds to generate substituted bicyclic, spiro, and fused nitrogen-containing heterocycles, all common motifs in various pharmaceutical and bioactive molecules.

First claim

What is claimed is:

1 . A compound of Formula (I):

or a salt thereof,
wherein:
each R 1 independently is branched or unbranched, substituted or unsubstituted, cyclic or acyclic aliphatic; branched or unbranched, substituted or unsubstituted, cyclic or acyclic heteroaliphatic; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl;
A is substituted or unsubstituted arylene; or substituted or unsubstituted heteroarylene;
L is branched or unbranched, substituted or unsubstituted, cyclic or acyclic aliphatic; or branched or unbranched, substituted or unsubstituted, cyclic or acyclic heteroaliphatic;
X is S, O, or NR X , wherein R X is hydrogen; nitrogen protecting group; branched or unbranched, substituted or unsubstituted, cyclic or acyclic aliphatic; branched or unbranched, substituted or unsubstituted, cyclic or acyclic heteroaliphatic; substituted or unsubstituted arylene; or substituted or unsubstituted heteroarylene;
M is a transition metal; and
n is an integer between 2 and 10, inclusive;

wherein the atom X labeled “*” of one monomer is bonded to the transition metal M labeled “**” of another monomer.

2 . The compound of claim 1 , wherein each R 1 independently is a substituted or unsubstituted aryl.

3 . The compound of any one of claims 1 - 2 , wherein each R 1 is the same.

4 . The compound of claim 1 , wherein each R 1 is phenyl.

5 . The compound of any one of claims 1 - 4 , wherein A is unsubstituted arylene.

6 . The compound of any one of claims 1 - 4 , wherein A is phenylene.

7 . The compound of any one of claims 1 - 6 , wherein L is unbranched, unsubstituted, acyclic aliphatic.

8 . The compound of any one of claims 1 - 6 , wherein L is —CH 2 —.

9 . The compound of any one of claims 1 - 8 , wherein X is O.

10 . The compound of any one of claims 1 - 9 , wherein M is a transition metal selected from the group consisting of iron, cobalt, and nickel.

11 . The compound of any one of claims 1 - 9 , wherein M is iron.

12 . The compound of any one of claims 1 - 11 , wherein n is an integer between 4 and 8, inclusive.

13 . The compound of any one of claims 1 to 12 , wherein the compound is of formula:

wherein:
each R 1 independently is branched or unbranched, substituted or unsubstituted, cyclic or acyclic aliphatic; branched or unbranched, substituted or unsubstituted, cyclic or acyclic heteroaliphatic; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl; M is a transition metal selected from the group consisting of iron, cobalt, and nickel; and
n is an integer between 2 and 10, inclusive;

wherein the oxygen atom labeled “*” of one monomer is attached to the transition metal M labeled “**” of another monomer.

14 . The compound of any one of claims 1 to 13 , wherein the compound is of formula:

wherein:
each R 1 independently is substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl;
M is a transition metal selected from the group consisting of iron, cobalt, and nickel; and
n is an integer between 2 and 10, inclusive;

wherein the oxygen atom labeled “*” of one monomer is attached to the transition metal M labeled “**” of another monomer.

15 . The compound of any one of claims 1 to 14 , wherein the compound is of formula:

wherein:
each R 1 independently is substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl;
M is a transition metal selected from the group consisting of iron, cobalt, and nickel; and
n is 6;

wherein the oxygen atom labeled “*” of one monomer is attached to the transition metal M labeled “**” of another monomer.

16 . The compound of any one of claims 1 to 15 , wherein the compound is of formula:

and
each R 2 is of the formula

17 . The compound of any one of claims 1 to 15 , wherein the compound is of formula:

and
each R 2 is of the formula

18 . The compound of any one of claims 1 to 15 , wherein the compound is of formula:

and
each R 2 is of the formula

19 . A compound of Formula (I-a):

or a salt thereof,
wherein:
each R 1 independently is branched or unbranched, substituted or unsubstituted, cyclic or acyclic aliphatic; branched or unbranched, substituted or unsubstituted, cyclic or acyclic heteroaliphatic; substituted or unsubstituted aryl; or substituted or unsubstituted heteroaryl;
A is substituted or unsubstituted arylene; or substituted or unsubstituted heteroarylene;
L is branched or unbranched, substituted or unsubstituted, cyclic or acyclic aliphatic; or branched or unbranched, substituted or unsubstituted, cyclic or acyclic heteroaliphatic; and
X is S, O, or NR X , wherein R X is hydrogen; nitrogen protecting group; branched or unbranched, substituted or unsubstituted, cyclic or acyclic aliphatic; branched or unbranched, substituted or unsubstituted, cyclic or acyclic heteroaliphatic; substituted or unsubstituted arylene; or substituted or unsubstituted heteroarylene.

20 . The compound of claim 19 , wherein each R 1 independently is a substituted or unsubstituted aryl.

21 . The compound of any one of claims 19 - 20 , wherein each R 1 is the same.

22 . The compound of claim 19 , wherein each R 1 is phenyl.

23 . The compound of any one of claims 19 - 22 , wherein ring A is unsubstituted arylene.

24 . The compound of any one of claims 19 - 22 , wherein ring A is phenylene.

25 . The compound of any one of claims 19 - 24 , wherein L is unbranched, unsubstituted, acyclic aliphatic.

26 . The compound of any one of claims 19 - 24 , wherein L is —CH 2 —.

27 . The compound of any one of claims 19 - 26 , wherein X is O.

28 . The compound of claim 19 , wherein the compound is of the formula:

29 . A compound of Formula (II):

or a salt thereof,
wherein:
each R 3 independently is hydrogen; branched or unbranched, substituted or unsubstituted, cyclic or a

Assignees

• Harvard College

Inventors

• Betley Theodore Alexander
• Mikhailine Alexandre
• Kleinlein Claudia
• Dong Yuyang
• Baek Yunjung

Classifications

• C07D211/70

  with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to ring carbon atoms · CPC title

• C07D207/08

  with hydrocarbon radicals, substituted by hetero atoms, attached to ring carbon atoms · CPC title

• B01J2531/845

  Cobalt · CPC title

• C07F15/06

  Cobalt compounds · CPC title

• C07D209/44

  Iso-indoles; Hydrogenated iso-indoles · CPC title