LONG-RANGE GOAL: Selective amination of CH-bonds in Cu – [nitrene]

systems

R-H + PhI=NTs NTs + PhIR

H

SYSTEMS FOR DIRECT HYDROCARBON AMIDATION SYSTEMS FOR DIRECT HYDROCARBON AMIDATION

PhI=NTs / Mn porphyrinate PhI=NTs / Rh2(OAc)4 ButOOCONHTs / Cu(OTf)2 TsNCl(Na) / Cu(II)

Ru(salen)(PPh3)2

Ru(Tp)(PPh3)2Cl

[RuCl2(cod)]n

RuCl3·x H2O

Reaction condition: 1.1 equ of substrate, r.t.3 h2 mol % of catalyst

SUBSTRATE / AMIDATION SELECTIVITYSUBSTRATE / AMIDATION SELECTIVITY

IN SITU PREPARATION of PhI=NTs ?IN SITU PREPARATION of PhI=NTs ?

PhI(OAc)2 + H2NR PhI=NR + 2 AcOH

OTHER AMIDES H2NR AS A SOURCE OF NHR ?OTHER AMIDES H2NR AS A SOURCE OF NHR ?

H2NSO2Me PhI=NSO2Me ?

H2NCOPh PhI=NCOPh ?

X X

NHTs

PhI=NTs

krel

SOME MECHANISTIC ASPECTSSOME MECHANISTIC ASPECTS

SOME MECHANISTIC ASPECTSSOME MECHANISTIC ASPECTS

PhI=NTsNHTs

-d10

kH / kD = 6.5-6.1or

[Mn]=NTsRH [Mn] + R-NHTs-R

.R

.[Mn]-NHTs

SOME MECHANISTIC ASPECTSSOME MECHANISTIC ASPECTS

Mechanism, postulated for Mn-porphyrin systems:

[Ru(N‑N)2Cl2] + PhI=NTs [Ru(N‑N)2(NTs)Cl]+

ES-MS, m/z = 756

PhI=NTs

> 95%

NTs

H

PhI=NTs

> 65%

N

Ts

H

PhI=NTs

> 40%

N

Ts

H

N

N

BrBr

Br

BH

3

TpBr3

JACS Communications2003, 125, 12078-12079

Cyclohexane and Benzene Amination by Catalytic Nitrene Insertion into C-H Bonds with the Copper-Homoscorpionate Catalyst

TpBr3Cu(NCMe) M. Mar Diaz-Requejo, Tomas R. Belderrain, M. Carmen Nicasio, Swiatoslaw Trofimenko,

Pedro J. Perez

R2

R1

R2

R1

R2

R1N H T s N T s

1-3 h+ +

up to 35%

N-arylamidescat. syst.

up to 45%

R1=Me, R2=H; R1=H, R2=H, 4-Me, 3,5-Me2

R2

R1

R2

R1

R2

R1N H T s N T s

1-3 h+ +

up to 35%

N-arylamidescat. syst.

up to 45%

R1=Me, R2=H; R1=H, R2=H, 4-Me, 3,5-Me2

NHTs

12 h+ +

18% 16% 2%

cat. syst.

NHTs

SIMPLE Cu CATALYSTS FOR CH AMINATIONSIMPLE Cu CATALYSTS FOR CH AMINATION

CuN

Cl

ClN

OUR FINDINGS: 1) Alkane amination AND dehydrogenation/aziridination:

2) Alkylarene amination AND amine dehydrogenation:

3) Simple CuII complexes are efficient catalysts of these reactions:

Activity of catalysts increases in the presence of NaBArF4

CuN

N

ClCl

Cl

Cu

Cl

N

N CuN

N

Cl

Cl

Cu NN

Cl

Cl

CuN

N

Cl

Cl

CuN

N

Cl

ClR

(py)2CuCl2[(dpm)CuCl 2]2 (Me-dpm)CuCl 2

[(dipy)CuCl2]n

2.29 Å

2.67 Å

2.26 Å

2.31 Å

2.26 Å

2.31 Å

2.22 Å

2.24 Å

EXAMPLE OF OLEFIN AZIRIDINATIONEXAMPLE OF OLEFIN AZIRIDINATION

Table 1. Results of olefin aziridination with 1 equivalent of PhINTs in the presence of 5 mol % of (L’)CuCl2 and no or 2

equivalents of NaBArF4 in CHCl3 at 296 K

Entry Substrate Yield of aziridine, % on olefin (time, min)

dpm dpp Cl-dpm Me-dpm (py)2 dipy

2 equivalents of NaBArF4 per (L’)CuCl2

1 cis-Cyclooctene 66 (1) 82 (1) 83 (1) 67 (5) 83 (1) 73 (10)

2 Styrene 95 (1) 95 (1) 98 (1) 93 (2) 97 (10) a 98 (5)

3 Tetramethylethylene 76 (5) 81 (5) 91 (2) 75 (1) 94 (2) 50 (5)

4 tert-Butylethylene 49 (10) 60 (3) 63 (5) 31 (40) 55 (3)

5 Methyl acrylate 35 (30) 45 (30) 45 (20) 38 (25) 44 (5)

No NaBArF4

6 Styrene 97 (20) 81 (5) 65 (20) 92 (5)

7 Tetramethylethylene 51 (30) 67 (2) 55 (30) 89 (2)

8 cis-Cyclooctene 50 (15) 57 (1) 36 (60) 71 (2)

9 tert-Butylethylene 21 (30) 19 (15) 31 (15) a 1 mol % of catalyst

PhINTs

PhIL Cu2+

a

[LCuIII(NTs)]2+

b

c

[LCuIII(NHTs)]2+

(singlet)

[LCuII(NHTs)]2+

(triplet)

[LCuIINH2Ts]2+

TsHN

+

A+1

+1

PLAUSIBLE MECHANISM OF CH AMINATIONPLAUSIBLE MECHANISM OF CH AMINATION

Facts in support of the scheme above: Addition of PhINTs to CuII complex causes its color change from blue to yellow (CuIII?). The yellow color is gone when PhINTs reacted completely. Additional hypotheses: 1) Dinuclear Cu complexes are responsible for alkane and amine dehydrogenation2) Efficiency of Cu catalyst is a function of the ability of L to withstand oxidative degradation 3) Part of PhINTs forms less active nitrene “dimers” TsN=NTs

QUESTIONS / PLANS FOR FUTUREQUESTIONS / PLANS FOR FUTURE

• Are the reaction products, N-tosylamides / aziridines, - good or “bad” ligands for CuII –based catalysis of nitrene transfer?

• What is the catalyst resting state?

• If they are poor ligands, how to modify pyridine ligands to achieve a better performance to cost ratio?

• Is it possible to detect spectroscopically (NMR, UV-Vis etc) plausible CuIII - nitrene adducts?

• Is it possible to prepare such robust ligands which will allow isolation of Cu-nitrene adducts?

• Will dinuclear-only Cu-complexes be more efficient in catalytic dehydrogenation?

• Is it possible to use TsN=NTs as a source of NTs?

• How reactivity of Cu-nitrene adducts will be influenced by the nature of R group in nitrenes RN? Is it possible to enhance their reactivity so that methane CH bonds can be attacked? Or tune their reactivity so that only selective CH bond cleavage will occur (3o-only, e.g.)?