PRIMARY ALCOHOLS FROM TERMINAL PRIMARY ALCOHOLS FROM TERMINAL OLEFINS: FORMAL ANTI-OLEFINS: FORMAL ANTI-

MARKOVNIKOV HYDRATION VIA MARKOVNIKOV HYDRATION VIA TRIPLE RELAY CATALYSISTRIPLE RELAY CATALYSIS

Guangbin Dong, Peili Teo, Zachary K. Wickens, Robert H. Grubbs Science 2011, 333, 1609.

Shawn K. CollinsShawn K. CollinsUniversitUniversitéé de Montr de Montrééalal

Department of ChemistryDepartment of ChemistryCentre for Green Chemistry and CatalysisCentre for Green Chemistry and Catalysis

shawn.collins@umontreal.caWeb: Web: http://www.mapageweb.umontreal.ca/collinss/

CHARETTE/COLLINS LITERATURE MEETINGCHARETTE/COLLINS LITERATURE MEETINGUniversité de Montréal (UdeM)Université de Montréal (UdeM)

March 12March 12thth, 2014, 2014Montréal, QuébecMontréal, Québec

1.

2. NaOH, H2O2

OHOB

OH

11.5 : 1 selectivity for primary olef ins

Boron-containing wastes sometimes dif f icult to removeHydrogen peroxide poses problems upon scale-up

OH

H2O

Catalyst

STOICHIOMETRIC SYNTHESIS OF PRIMARY ALCOHOLS

Brown, H. C.; Gupta, S. K. J. Am. Chem. Soc. 1975, 97, 5249.

CATALYTIC SYNTHESIS OF PRIMARY ALCOHOLS

trans-PtHCl(PMe3)2NaOH

H2O: 1-hexene (1:1)60 C, BnEt3NCl

OH

6.9 turnovers/ h

Jensen, C. M.; Trogler, W. C. Science 1986, 233, 1069.

Later proved to “difficult to reproduce”• Marsella and co-workers prepared analytically pure “active” species and proved

it to be inactive

Ramprasad, D.; Yue, H. J.; Marsella, J. A. Inorg. Chem. 1988, 27, 3151.

HO

88 %

HO25 C, 12 h, C6D6

(TPP)RhH KOtBu

25 C, 1 hC6D6

O HO

71 %29 %

Rh(TPP) OH

Sanford, M. S.; Groves, J. T. Angew. Chem. Int. Ed. 2004, 43, 588 .

• Demonstrated each step of a catalytic cycle, but never completed the cycle!

CATALYTIC SYNTHESIS OF PRIMARY ALCOHOLS

One step reaction, but would require an additional saponification and hydrogenation.

81 %

O2 (1 atm), AcOH, 80 C, 18 h

Pd(OAc)2 (5 mol %)

N N

O

(5 mol %)OAc

Campbell, A. N.; White, P. B.; Guzei, I. A.; Stahl, S. S. J. Am. Chem. Soc. 2010, 132, 15116.

Stewart, I. C.; Bergman, R. G.; Toste, F. D. J. Am. Chem. Soc. 2003, 125, 8696.

95 %MeOH, 45 C, 6 h

PMe3 (5 mol %)

O O

OMe

Other work uses “activated” olefins…in this paper they comment that the hydration equivalent is an unknown transformation for organic synthetic

chemists….

Boersma, A. J.; Coquie`re, D.; Geerdink, D.; Rosati, F.; Feringa, B. L.; Roelfes, G. Nature Chem. 2010, 2, 991.

Using Cu catalysis and DNA…Feringa and co-workers finally accomplished this in 2010…

[M] H

R

O

R

O

H

[M]

[M] Cl

H-Cl

R

HO

PROPOSED CATALYTIC RELAY

PdCl2

R

R

PdCl Cl

H2O

RClPd

OH

R

OHClPd

trans hydroxy-palladation (external attack of water)

cis hydroxy-palladation (syn delivery of hydroxide)

or

R

PdH Cl

OH

R

Ovs.

R

O

H-Cl

[O]

Challenges include:•How to get aldehyde selectivity in the Wacker Oxidation (particularly for styrene

derivatives)• Which metal complex could participate in the reduction, and under aqueous

conditions?

WACKER OXIDATION

PdCl2 (12 mol %)H4[PMo11VO40] (1.2 eq.)

DMF:H2O (10:1), 18 h75%

O

O

+

6.4 : 1 selectivity

OH

PdL

L

f avored vs.

PdL

LOH

Wright, J. A.; Gaunt, M. J.; Spencer, J. B. Chem.-Eur. J. 2006, 12, 949.

PdCl2(MeCN)2 (20 mol %)CuCl2 (30 mol %)

O2 (1 atm), ROH, 50C, 30 min

n-C8H17O

n-C8H17

O

+

R = EtOH 16 : 84 selectivity, 22 %R = iPrOH 42 : 58 selectivity, 11 %R = tBuOH 84 : 16 selectivity, 7 %

n-C8H17

Ogura, T.; Kamimura, R.; Shiga, A.; Hosokawa, T. Bull. Chem. Soc. Jpn. 2005, 78, 1555.

Strategy:•PdCl2 complexes/styrene starting materials

• t-BuOH as solvent

PROPOSED CATALYTIC RELAY

PdCl2

Ar

Ar

PdCl Cl

t-BuOH

Art-BuO

PdCl

Ar

PdClt-BuO

trans hydroxy-palladation (external attack of water)

cis hydroxy-palladation (syn delivery of hydroxide)

or

Ar

PdH Cl

Ar

t-BuO

[M] H

Ar

O

Ar

O

H

[M]

H-Cl

[M] Cl H-Cl

t-BuO

?

[O]

Ar

HO

SHVO’S CATALYST

Shvo, Y.; Czarkie, D. J. Organomet. Chem. 1986, 315, C25.

Strategy:•Use Shvo’s catalyst but add alcohol as hydride source?

Casey, C. P.; Singer, S.; Powell, D. R.; Hayashi, R. K.; Kavana, M. J. Am. Chem. Soc. 2001, 123, 1090.

OPhPh

PhPh H

RuC

O CO

H

O Ph

Ph

Ph

PhRu

C

O

CO

Shvo's catalyst

OPhPh

PhPh H

RuC

O CO

H

O Ph

Ph

Ph

PhRu

C

O

CO

+O

PhPh

PhPh H

RuC

O CO

HO

H R

O Ph

Ph

Ph

PhRu

C

O

CO

H

HRR

O

OH OAc

Shvo catalyst (2 mol %)Novozym 435

4ClPhOAc (4 eq.)

PhMe, 70 C, 46 h80 %, > 99 % ee

Persson, B. A.; Larsson, A. L. E.; Le Ray, M.; Backvall, J.-E. J. Am. Chem. Soc. 1999, 121, 1645.

PROPOSED CATALYTIC RELAY: TRIPLE RELAY

PdCl2

Ar

Ar

PdCl Cl

t-BuOH

Art-BuO

PdCl

Ar

PdClt-BuO

trans hydroxy-palladation (external

attack of water)

cis hydroxy-palladation (syn delivery of

hydroxide)

Ar

PdH Cl

Ar

t-BuO

Ar

O

H-Cl

OPhPh

PhPh H

RuC

O CO

H

t-BuO

?

OPh

Ph

Ph

PhRu

C

O

CO

H

H H

O Ar

O

PhPh

PhPh

RuC

O CO

OH

MeMe

O

MeMe[O]

Ar

HO

PROPOSED CATALYTIC RELAY: TRIPLE RELAY

PdCl2

Ar

Ar

PdCl Cl

t-BuOH

Art-BuO

PdCl

Ar

PdClt-BuO

trans hydroxy-palladation (external

attack of water)

cis hydroxy-palladation (syn delivery of

hydroxide)

Ar

PdH Cl

Ar

t-BuO

Ar

OHCl + H2O O

PhPh

PhPh H

RuC

O CO

H

t-BuO

OPh

Ph

Ph

PhRu

C

O

CO

H

H H

O Ar

O

PhPh

PhPh

RuC

O CO

OH

MeMe

O

MeMe

t-BuOH

HCl becomes 3rd

catalyst !!!

[O]

PdCl2

Ar

HO

PRELIMINARY RESULTS

Controls:•No palladium catalyst 26 % of desired product (34 % conv.)

• No Shvo catalyst: only aldehyde product 42 %• No Shvo catalyst or water: 17 %

• No CuCl2: 48 % of desired product (32 % ethylbenzene)• No benzoquinone 58% conv, almost no by-products ???

• No iPrOH 57% aldehyde• No tBuOH 58% conv, 18 % desired product.

• No tBuOH but 28 eq. H2O 64 % desired product• no H2O, but 4A MS, 57 % ethyl benzene

Ot-Bu

Shvo's catalyst (10 mol %)PdCl2(MeCN)2 (10 mol %)

H2O (1.1 eq.)

CuCl2 (20 mol %)benzoquinone (80 mol %)iPrOD/tBuOD (1:2), 85 C

OD/H

69 %

DOD/H

D

+

D

31 %

Shvo's catalyst (10 mol %)PdCl2(MeCN)2 (10 mol %)

H2O (1.1 eq.)

CuCl2 (20 mol %)benzoquinone (80 mol %) /tBuOD (1:2), 85 C

OD/H

65 %

DOD/H

D

+

D

35 %

OD

MeMeD

D D

Shvo's catalyst (10 mol %)PdCl2(MeCN)2 (10 mol %)

H2O (1.1 eq.)

CuCl2 (20 mol %)benzoquinone (80 mol %)iPrOH/tBuOH (1:2), 85 C

OH

77 %

OH

1.3 % 0.7 %

OO

1.4 % 1.5 %

SCOPE

R

Shvo's catalyst (10 mol %)PdCl2(MeCN)2 (10 mol %)

H2O (1.1 eq.)

CuCl2 (20 mol %)benzoquinone (80 mol %)iPrOH/tBuOH (1:2), 85 C

ROH

OH

84 %

OH

42 %

OH

61 %

OH

60 %

OH

72 %

OH

75 %

OH

72 %

OH

63 %

OH

83 %

OH

74 %Cl FBr O2N

F3C

CF3

OHOH

56 % 12 %

>20 : 1 >20 : 1 >20 : 1 >20 : 1 >20 : 1

>20 : 1>20 : 1>20 : 1>20 : 1>20 : 1

1 : 1.4 1 : 2.1

SUMMARY.

Compared to the classic hydroboration/oxidation sequence, our approach is still far from perfect, with its relatively high catalyst loadings and use of stoichiometric BQ. However, we are strongly encouraged by the excellent selectivity with arylsubstituted olefins, initial promising results with aliphatic alkenes, and the facile recovery of BQ to reduce the overall expense. Despite being in its infancy, this methodology has demonstrated great potential and will stimulate ongoing research in the field of olefin hydration

EXTENSION TO HYDROAMINATION

NMePh1) PdCl2(PhCN)2 (10 mol %)

BQ (1 eq.), H2O, t-BuOH, 35 C

2) N-Me aniline (2.5 eq.) Ir catalyst (10 mol %)

5:2 formic acid:TEA azeotrope, 85 C66 %

N

MeO

OMe

Ir Cl

Bronner, S. M.; Grubbs, R. H. Chem. Sci. 2014, 5, 101.