Catalyst-free and redox-neutral innate trifluoromethylation and alkylation of (hetero)aromatics enabled by light

Patent metadata

Field	Value
Publication number	US-11098036-B2
Application number	US-201816649269-A
Country	US
Kind code	B2
Filing date	Sep 28, 2018
Priority date	Sep 29, 2017
Publication date	Aug 24, 2021
Grant date	Aug 24, 2021

Abstract

The present disclosure relates to reagents and method for performing trifluoromethylation, difluoromethylation or alkylation of aromatic or heteroaromatic rings in a redox-neutral manner without any catalyst which are enabled by light. In addition, there are methods for synthesizing the starting reagents used in the trifluoromethylation, difluoromethylation or alkylation reactions.

First claim

The invention claimed is:

1. A method for forming a compound of formula:

wherein

defines a mono or polycyclic aryl ring or a mono or polycyclic heteroaryl ring;
each Ra is independently selected from H or an optional substituent;
R 2 is CF 3 , CF 2 H, a linear alkyl of 2 or more carbon atoms, a branched alkyl of 3 or more carbon atoms or a cycloalkyl of 3 or more carbon atoms; and
m is an integer of 1 to 5;
comprising:
i) mixing together a compound of formula:

wherein R 1 is H, or an optional substituent;
R 2 is as defined above;
R 3 is H, or a C1-C6 linear alkyl, C3-C6 branched alkyl or C3-C6 cycloalkyl;
or R 1 and R 3 , together with the atoms to which they are attached, form a 5-6 membered ring;
each R is independently selected from H or an optional substituent;
n is an integer of 1 to 4;
with compound of formula:

wherein

is as defined above, and Ra and m are as defined above;
ii) photo irradiating the mixture of step i) to provide said compound of formula (II).

2. The method of claim 1 wherein said aryl ring is a 6 membered monocyclic or 9-10 membered bicyclic benzenoid-type ring.

3. The method of claim 1 wherein said heteroaryl is monocyclic 5-6 membered or a 9-10 membered fused-bicyclic or 12-14 membered fused tricyclic ring.

4. The method of claim 1 , wherein R 1 and R 3 , together with the atoms to which they are attached, form a 5 membered ring or wherein R 1 is H and R3 is H, or a C1-C6 linear or C3-C6 branched alkyl.

5. The method of claim 1 , wherein R 2 is CF 2 H.

6. The method of claim 1 , wherein the linear alkyl of group R 2 is an alkyl of 2 to 10 carbon atoms, wherein the branched alkyl of group R 2 is a branched alkyl of 3 to 8 carbon atoms and wherein the cycloalkyl of group R 2 is a cycloalkyl of 3 to 8 carbon atoms.

7. The method of claim 1 , wherein R or Ra is each independently and each time selected from halogen, C1-6alkyl, C2-6alkenyl, C1-6 alkoxy, substituted C1-6 alkoxy, aryl, oxo (C═O), cyano (CN), —NR40R41, —C(O)NR40R41, —NR40COR41, carboxy, hydroxyl, nitro, —SR40, —S(O) 0-2 R40, —C(O)R40, —C(O)OR40 or —SO 2 NR40R41; wherein R40 and R41 are each independently H, or C1-6alkyl.

8. The method of claim 1 , wherein R is H or C1-6alkyl.

9. The method of claim 1 , wherein Ra is H, C1-6alkyl, C1-6 alkoxy, aryl, hydroxyl, or —C(O)OR40 wherein R40 and R41 are each independently H, or C1-6alkyl.

10. A method for forming a compound of formula:

comprising:
1) reacting a compound of formula

with a compound of formula
R 2 —S − X+  (V)

wherein R 1 ; R 3 ; R, and n are as defined in claim 1 ; and R 2 is a linear alkyl of 2 or more carbon atoms, a branched alkyl of 3 or more carbon atoms or a cycloalkyl of 3 or more carbon atoms;
L is a leaving group
X + is a counterion;
to provide a compound of formula

wherein R 1 ; R 2 ; R 3 ; R, and n are as defined above; and
2) reacting said compound of formula (VI) with an oxidant to provide said compound of formula (I).

11. A compound of formula:

wherein
R 2 is CF 3 , and
R 1 and R 3 , together with the atoms to which they are attached, form a 5-6 membered ring.

12. The compound of claim 11 , which is

Assignees

• The Royal Institution For The Advancement Of Learning/Mcgill Univ

Inventors

• Li Chao-Jun
• Liu Wenbo
• Liu Peng

Classifications

• C07D311/30

  not hydrogenated in the hetero ring, e.g. flavones · CPC title

• C07D207/33

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

• C07C17/32

  by introduction of halogenated alkyl groups into ring compounds · CPC title

• C07D215/48

  Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen · CPC title

• C07C67/343

  by increase in the number of carbon atoms · CPC title