DehydrogenationofPrimaryAlcoholsand

RelatedCatalytic OrganicReactions
Part 1. Inner- and outer-sphere catalysts

DmitryG.Gusev,ProfessorofChemistry
Wilfrid LaurierUniversity,Waterloo,Ontario,Canada

Outline

1.
2.
3.
4.
5.

Inner andouterspherecatalysts
Transferhydrogenation
Acceptorless dehydrogenative coupling
Dehydrogenative reactionswithamines
Hydrogenationofestersandamides

Dehydrogenation vs. hydrogenation

Different ways of looking at the same reaction, involving the same catalyst

dehydrogenation

hydrogenation

Dehydrogenation of primary alcohols - why?

G > 0

OH

R'

NH2

R'

NH2

O
R

O
+ H2

O
R

R'
+ H2O

N
H

R'

R
+ H2

N
H

R'

Green reactions: highly selective, mild, non-toxic, producing no waste, no solvent.

Mechanisms/Catalysts for alcohol dehydrogenation:

1. Inner-sphere (classical)
2. Outer-sphere
also referred to as Noyori-type, bifunctional, ligandassisted, and cooperative catalysis
1. Blended (?) in Milsteins catalysts

The Inner-Sphere Alcohol Dehydrogenation

Examples: RuCl2(PPh3)3, (5-Cp)RuCl(PPh3)2, [(5-Cp*)IrCl2]2
LnM L
Cl

tBuOK
H
HO
C
H
R

LnM L
O
KCl, tBuOH

18-e

This step may not

be needed with
16-e catalysts

LnM
H

18-e

LnM L
O

O
L

18-e

H
C

The key species

16-e
-hydrogen elimination
LnM

L nM
O

H
C

R
16-e

C H
R

16-e

Note: the metal oxidation state is unchanged when the alcohol is oxidized. What is the oxidant?

Catalyst Recycling (dehydrogenation)

After alcohol dehydrogenation, catalyst recycling requires H2 release (gas
formation) or transfer to another molecule (substrate or sacrificial H2 acceptor).
Acceptorles H2 gas elimination is possible but rare:

Note: late TM hydrides are often not hydridic and alcohols are typically not acidic. Therefore,
protonation of M-H by ROH can be slow and H2 formation and elimination may require heating
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Alcohol dehydrogenation via Transfer hydrogenation

H

HO
LnM L

+
tBuOK

Cl

LnM L
O

H
C

R1

LnM

OH

R2

H
C

R1

C H
R

LnM

Consumed
as produced

O
C

Product

R
LnM O

+ tBuOH

H
L

By-product
(useful or not)

+ KCl

R2
LnM
O
HO

R2

H
C

R1

C
R2

R1

H2 acceptor:
Carbonyl compounds,
imines, olefins, alkynes
CO2

Substrate

Potential problems: poor thermal cat. stability, easy deactivation via alcohol
decarbonylation or when the substrate has a coordinating group

The Outer-sphere Alcohol Dehydrogenation Catalysts

Hydrogenated form of the catalyst

Dehydrogenation catalyst
16-e amido

Lewis acidic site

Basic site

Noyori catalyst

Pri

Ph

Note the bifunctional

nature of the catalysts
and ligand cooperation

Pri
Ru

Tos

When present, the trans-ligand

often has a strong trans-effect

H2

NH
Ph

H
H

Tos
O

Ph

Ru

+
O

Ph H

16e,Ru(II)

18e,Ru(II)

16e,Rh(I)

18e,Rh(I)

Grtzmacher

The Outer-sphere Alcohol Dehydrogenation Catalysts

No need for direct bonding between the basic and acidic sites:
Hydrogenation
catalyst

Shvo catalyst

Ph
Ph
Ph

Ph

O H O
Ph
Ru

OC CO

Ph
Ru
CO

Ph
Ph
CO

Ph
Ph

Ph

Ru

OC CO

Dehydrogenation
catalyst

OH
Ph
H

18-e, Ru(II)

Ph
+

Ph
OC

Ph

basic site

Ph
Ru
CO

acidic site

16-e, Ru(0)

Shvo bifunctional catalyst is one of

the few that are active without base

16-e, Ru(II)
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Outer-sphere Catalyst Generation

L'

L'
N
H

MLn

Cl
pre-catalyst
18-e

base

1)

MLn

-baseHCl

1) H-H
the catalyst
16-e

L'

2) acceptor

2) acceptor H-H

MLn

H
18-e

With rare exceptions, dehydrogenation is performed using base.

Working without base is desirable.

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The Key Steps in Outer-sphere Alcohol Dehydrogenation

The reaction is usually described as concerted transfer, that implies single TS.
Some computational work (including ours) shows two distinct transition states:
One for H+ transfer to the basic site, and the other for H- transfer to the metal.
LnM

NR2

(16e) amide

H+ transfer

Partial M-N double bond

Step 1

H
H
C O
H
R

LnM

Step 2

NR2
H

H
H

C
R

LnM

NR2
H

H
C

C-H 1.21 - 1.24

R
C-H agostic intermediate

H- transfer
(heterolytic
C-H activation)

LnM

NR2 18-e amino hydride

H
H

H
+

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Heterolysis vs. homolysis of C-H

Outer-sphere dehydrogenation involves C-H bond cleavage of a substrate that is not covalently
bonded (coordinated) to the metal. This is highly unusual in homogeneous catalysis. Yet, this
process has a very low energy barrier and it is extremely fast with best known catalysts (the work
of Grtzmacher). Why?

Typical C-H homolytic splitting costs in the range of 90 100 kcal/mol.

C-H heterolysis of alkoxides is considerably less costly, for example:

H = 38.6 kcal/mol (in the gas phase)

G = 16.6 kcal/mol (in CH3CN)
Compare with the superhydride:

H = 69.4 kcal/mol (in the gas phase)

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Outer-sphere transfer dehydrogenation of EtOH

S/C = 100,000, TOF = 500,000 at r.t.

H2 transfer is typically
shown as one step

Consumed as
produced

Grtzmacher et al.

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Problems in Outer-sphere Dehydrogenation

Metal alkoxide formation is the only, yet serious, problem:

Note: the alkoxide is often the more favourable product

(especially when M = Ru)
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Problems in Outer-sphere Dehydrogenation

5d (Os, Ir) metals are less prone to alkoxide formation compared to 4d metals (Ru).
Example from our recent work (Organometallics, 2011, ASAP):

The Os catalyst, compared to Ru, is 10 more efficient for alcohol dehydrogenation!

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Problems in Outer-sphere Dehydrogenation

Our DFT calculations estimate the barrier for dehydrogenation of EtOH to be lower by
3.8 kcal/mol vs. iPrOH, therefore the dehydrogenation of EtOH should be faster.
Unfortunately, primary metal alkoxides tend to be more stable than the secondary:

G, kcal/mol

+2.8

0.0

-3.9

0.0

Dehydrogenation of iPrOH with the Os catalyst is 100 times faster than that of EtOH!
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Blended Milstein catalyst

A bifunctional catalyst that can undergo -hydrogen elimination of the intermediate alkoxide

Milstein catalyst is one of the few dehydrogenation catalysts that can be used without base.

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Milstein catalyst at work

S/C = 1,000, 110 C (typical)

Used as produced
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Proving the outer-sphere mechanism

Very challenging and cannot be decided by looking at the structure. Basically, one has to be sure that
the bifunctional catalyst in question is not loosing an ancillary ligand under the reaction conditions. If
happens, this opens path for -H elimination (inner-sphere mechanism).

Noyori (outersphere)

Stradiotto (innersphere)
S/C=200:1,28C,<3h

18e,Ru(II)

2propanol +base

Acetophenone:
S/C=500:1,45C,15h
S/C=2000:1,82C,5m

Catalyticallyactivespecies:

2propanol +base
Inactivespecies:
Pri

Pri

Ru +

Ru
H2N
Ph

H N

Tos

Ph

``ThepresenceoftheNH2 terminusiscrucial.
TheNMe2 derivativegaveverypoorreactivity``

Me2N

H PPri2

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Difficulty knowing the mechanism

Another example from the recent work of Morris et all. Organometallics 2011, 30, 1236.

Inner- or outer-sphere?

Suggested mechanism (inner-sphere):

Authors found lack of reaction between

complex 2 and a stoichiometric amount of
acetophenone in THF-d8 at 25 or 50 C

-H elimination
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Conclusion
Very intelligent and exceptionally efficient catalysts can be developed for
dehydrogenation of alcohols and subsequent conversion to a range of useful
organic products.
What is better: inner-, outer-, or blended catalyst design?
Inner-sphere catalysts typically need heating (for the labile/hemilabile ligand
displacement) and base. This is generally not the best way.
Outer-sphere catalysts are very active at r.t. and can work without any base.
Blended hemilabile catalyst design can be extremely efficient for some
applications. At the moment this catalytic type is the least explored but looks
very promising.
Next, we will look at some prominent examples of catalytic applications
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