PCNHCP metal complexes and uses thereof

Patent metadata

Field	Value
Publication number	US-12441669-B2
Application number	US-202118042752-A
Country	US
Kind code	B2
Filing date	Aug 22, 2021
Priority date	Aug 24, 2020
Publication date	Oct 14, 2025
Grant date	Oct 14, 2025

Abstract

PCNHCP pincer metal complexes are useful as catalysts in various chemical reactions such as hydrogen isotope exchange (HIE) in C(sp3)-H and/or C(sp2)-H bond of an organic compound, e.g., a pharmaceutically active compound. The complexes are also useful in hydroboration of alkynes with excellent selectivity; and alkene isomerization with high stereo- and regioselectivity.

First claim

What is claimed is:

1. A metal complex of formula I:

wherein:
R 1 , R 2 , R 3 , and R 4 each independently is selected from the group consisting of (C 1 -C 18 )alkyl, (C 2 -C 18 )alkenyl, (C 3 -C 7 )cycloalkyl, —O—(C 1 -C 18 )alkyl, (C 3 -C 12 )heterocyclyl, a 6-14-membered aryl, and a 5-10-membered heteroaryl; or R 1 and R 2 , and/or R 3 and R 4 , together with the phosphorus atom to which they are attached form a heterocyclic ring optionally containing one or more heteroatoms selected from the group consisting of O, N, and S;
R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 each independently is selected from the group consisting of H, (C 1 -C 18 )alkyl, (C 2 -C 18 )alkenyl, (C 3 -C 7 )cycloalkyl, (C 3 -C 12 )heterocyclyl, a 6-14-membered aryl, a 5-10-membered heteroaryl, —CF 3 , —OR, —SR, and —NRR′, or any two of adjacent R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 together with the carbon atoms to which they are attached form a 5-14-membered ring optionally containing one or more heteroatoms selected from the group consisting of O, N, and S;
M is an earth-abundant metal having an oxidation state selected from the group consisting of −2, −1, 0, +1, +2, +3, +4, +5, and +6;
X, Y and Z each independently is selected from the group consisting of H, deuterium (D), tritium (T), N 2 , CO, NO, N 2 O, (C 1 -C 18 )alkyl, (C 2 -C 18 )alkenyl, (C 3 -C 7 )cycloalkyl, —O—(C 1 -C 18 )alkyl, (C 3 -C 12 )heterocyclyl, a 6-14-membered aryl, a 5-10-membered heteroaryl, halogen, azide (N 3 − ), cyanide (CN − ), cyanate (OCN − ), isocyanide (RNC), isocyanate (RNCO), thiocyanate (SCN − ), isothiocyanate (RNCS), sulfide (S 2− ), oxo (O 2− ), peroxo (R—O—O), hydroperoxo (H—O—O − ), superoxide (O 2 − ), —NRR′, —SR, and a coordinating solvent; or one of X, Y and Z is selected from the group consisting of H, D and T, and the other two of X, Y and Z form a bidentate ligand;
R and R′ each independently is selected from the group consisting of H, (C 1 -C 18 )alkyl, (C 2 -C 18 )alkenyl, (C 3 -C 7 )cycloalkyl, (C 3 -C 12 )heterocyclyl, a 6-14-membered aryl, a 5-10-membered heteroaryl, and a trialkylsilyl;
Q is an optional counter ion; and
the asterisk represents an optional net charge of said metal complex which depends on the oxidation state of said metal and the groups X, Y and Z,
provided that at least one of X, Y and Z each independently is selected from the group consisting of H, D, and T.

2. The metal complex of claim 1 , wherein:
(i) R 1 , R 2 , R 3 , and R 4 each independently is selected from the group consisting of (C 1 -C 8 )alkyl, (C 3 -C 6 )cycloalkyl, and a 6-10-membered aryl; or
(ii) R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 each independently is H or (C 1 -C 8 )alkyl, or any two of adjacent R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 together with the carbon atoms to which they are attached form a 5-10-membered ring optionally containing one or more heteroatoms selected from the group consisting of O, N and S; or
(iii) X, Y and Z each independently is selected from the group consisting of H, D, T, N 2 , and CO; or one of X, Y and Z is selected from the group consisting of H, D and T, and the other two of X, Y and Z form a bidentate ligand; or
(iv) M is selected from the group consisting of Fe, Mn, Ni, and Co, having an oxidation state selected from −2, −1, 0, +1, +2, and +3.

3. The metal complex of claim 2 , wherein:
(i) R 1 , R 2 , R 3 , and R 4 each independently is a branched (C 1 -C 6 )alkyl; or
(ii) R 5 , R 7 , R 8 , and R 10 each is H.

4. The metal complex of claim 3 , wherein R 1 , R 2 , R 3 , R 4 R 6 , and R 9 each is isopropyl or tert-butyl.

5. The metal complex of claim 1 , wherein:
R 1 , R 2 , R 3 , and R 4 each independently is selected from the group consisting of (C 1 -C 8 )alkyl, (C 3 -C 6 )cycloalkyl, and a 6-10-membered aryl;
R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 each independently is H or (C 1 -C 5 )alkyl, or any two of adjacent R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 together with the carbon atoms to which they are attached form a 5-10-membered ring optionally containing one or more heteroatoms selected from the group consisting of O, N, and S;
X, Y and Z each independently is selected from the group consisting of H, D, T, N 2 , and CO, or one of X, Y and Z is selected from the group consisting of H, D and T, and the other two of X, Y and Z form a bidentate ligand; and
M is selected from the group consisting of Fe, Mn, Ni, and Co, having an oxidation state selected from −2, −1, 0, +1, +2, and +3.

6. The metal complex of claim 5 , wherein R 1 , R 2 , R 3 , and R 4 each independently is a branched (C 1 -C 6 )alkyl; and R 5 , R 7 , R 8 , and R 10 each is H.

7. The metal complex of claim 6 , wherein R 1 , R 2 , R 3 , R 4 , R 6 , and R 9 each is isopropyl or tert-butyl.

8. The metal complex of claim 7 , wherein;
(i) R 1 , R 2 , R 3 , and R 4 each is isopropyl; and R 6 and R 9 each is tert-butyl; and/or
(ii) M is selected from the group consisting of Fe, Co, and Mn.

9. The metal complex of claim 8 , wherein R 1 , R 2 , R 3 , and R 4 each is isopropyl; R 5 , R 7 , R 8 , and R 10 each is H; R 6 and R 9 each is tert-butyl; and:
(i) X and Y each is H or D; Z is N 2 ; and M is Fe having an oxidation state of +2 (herein identified complex I 1 or I 2 , respectively);
(ii) X and Z each is CO; Y is H or D; and M is Mn having an oxidation state of +1 (herein identified complex I 3 or I 4 , respectively);
(iii) X, Y and Z each is H or D; and M is Fe having an oxidation state of +2 (herein identified complex I 5 or I 6 , respectively);
(i) one of X, Y and Z is H or D; the other two of X, Y and Z form the bidentate ligand η 2 -H 2 Bpin; and M is Fe having an oxidation state of +2 (herein identified complex I 7 or I 8 , respectively); or
(ii) one of X, Y and Z is H or D; the other two of X, Y and Z form the bidentate ligand η 2 -H 2 BH 2 ; and M is Fe having an oxidation state of +2 (herein identified complex I 9 or I 10 , respectively).

10. A metal complex of formula II:

wherein:
R 1 , R 2 , R 3 , and R 4 each independently is selected from the group consisting of (C 1 -C 18 )alkyl, (C 2 -C 18 )alkenyl, (C 3 -C 7 )cycloalkyl, —O—(C 1 -C 18 )alkyl, (C 3 -C 12 )heterocyclyl, a 6-14-membered aryl, and a 5-10 membered heteroaryl; or R 1 and R 2 , and/or R 3 and R 4 , together with the phosphorus atom to which they are attached form a heterocyclic ring optionally containing one or more heteroatoms selected from the group consisting of O, N, or and S;
R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 each independently is selected from the group consisting of H, (C 1 -C 18 )alkyl, (C 2 -C 18 )alkenyl, (C 3 -C 7 )cycloalkyl, (C 3 -C 12 )heterocyclyl, a 6-14-membered aryl, a 5-10-membered heteroaryl, —CF 3 , —OR, —SR, and —NRR′, or any two of adjacent R 5 , R 6 , R 7 , R 8 , R 9 , and R 10 together with the carbon atoms to which they are attached form a 5-14-membered ring optionally containing one or more heteroatoms each independently selected from the group consisting of O, N or and S;
M is an earth-abundant metal having an oxidation state selected from the group consisting of −2, −1, 0, +1, +2, +3, +4, +5, and +6;
X and Y each independently is selected from the group consisting of H, deuterium (D), tritium (T), N 2 , CO, NO, N 2 O, (C 1 -C 18 )alkyl, (C 2 -C 18 )alkenyl, (C 3 -C 7 )cycloalkyl, —O—(C 1 -C 18 )alkyl, (C 3 -C 12 )heterocyclyl, a 6-14-membered aryl, a 5-10-membered heteroaryl, h

Assignees

• Technion Res & Dev Foundation

Inventors

• De Ruiter Graham
• Garhwal Subhash

Classifications

• C07F15/02

  Iron compounds · CPC title

• C07C2523/745

  Iron · CPC title

• C07B2200/05

  Isotopically modified compounds, e.g. labelled · CPC title

• C07B59/00

  Introduction of isotopes of elements into organic compounds {; Labelled organic compounds per se} · CPC title

• B01J2531/842

  Iron · CPC title