sean parris, olefin bisfunctionalisation the ad catalytic cycle chem. rev. 1994, 94, 2483-2547

Sean Parris, Olefin Bisfunctionalisation

The AD Catalytic Cycle

O

Os

L*

OOO

R

R

HO

R

OH

R

R

R

R

R

O

Os OOO

O

HO

R

OH

R

R

R

O

Os OOO

OR

R

R

RO

OsOO

OL*

L*

PrimaryCycle

SecondaryCycle

high e.e.

low e.e.

L*

H2O

H2O

[O]

A

B

C

Os(VIII)

Os(VI)

Os(VIII)

Os(VI)

Chem. Rev. 1994, 94, 2483-2547


Shutting Down the Secondary Cycle

O

Os

O

OOHO

HOO

Os

O

OHOHHO

HO

HO

R

OH

R

O

Os

L*

OOO

R

R

R

R

O

OsOO

O

+ L*

2 OH2 H2O

Organic Phase

Aqueous Phase

2 H2O2 Fe(CN)6

2 OH2 Fe(CN)6

3 4

+ L*

2 22 OH

Os(VI) Os(VIII)

Os(VI)

Os(VIII)


The Cinchona Alkaloids

(DHQ)2PHAL“AD-”


The AD-Mix Mnemonic

Works best for:• trans alkenes • terminal olefins quite bad• with aromatic ring to sit in “attractive area”


Which Ligand System?


Racemic Dihydroxylation – Beyond Upjohn

Upjohn (NMO, OsO4) can be slow & prone to over-oxidation

J. Eames, H. Mitchell, A. Nelson, P. O’Brien, S. Warren, P. Wyatt, Perkin 1 1999, p1095


Sharpless Asymmetric Aminohydroxylation (AA)


Sharpless et al. Angew. Int. 1997 438

Sharpless Asymmetric Aminohydroxylation (AA)


AA –Mechanism

Review: McLeod et al, Perkin 1, 2002, 2733


AA – Standard Conditions?

Review: P. O’Brien, Angew. Int, 1999, 326


Competing Dihydroxylation

• First turnover of catalyse is AD• Can reduce AD with slow addition of substrate


AA – Best Substrates

Cinnamates best using (DHQ)2PHAL (as drawn)

(DHQ)2AQN (regioisomer)

,-unsat’d(DHQ)2PHAL (as drawn)

effect ligand unknown


AA – More Substrates

-Styrenes, ,-unsat’d esters & vinyl arenes only work with acetamide & carbamate- Other egs where DHQ vs DHQD give regioisomers in similar ee of opposite stereoinduction!


Sharpless Aminohydroxylation – Further Work

,-unsat’d amides & carboxylic acids found to be good substrates for a racemic AH (Angew. 1997, p2751; Angew. 2001 3455) because exist solely in “secondary cycle”

Start to develop a AA using the secondary cycle only which places far more stringent requirements on the ligand, with only partial success: 50-70% ee for AD, 25-60% ee for AA (Angew. 2002, 474)

Muniz et al got around the problem of a racemic AH for acrylamindes by using chiral substrate (Tet. Asymm. 2005, 3492)

Hergenrother et al found could change regioselectivity in AA of styrenes by controlling pH with modest ee (Org. Let. 2003, 281)


Other Aminhydroxylations - TA

Tethered Aminohydroxylation (TA)

Donohoe et al, JACS 2002, 12934

• Stereochemistry comes from allylic alcohol• Stereoinduction requires cyclic system


Tethered Aminohydroxylation


Tethered Aminohydroxylation - Mechanism


Diamination to Conjugated Dienes

(1) disfavour 3 (2) favour Nu addn to give diamine (3) amine souce that won’t react with other species


Question Time – Predict the Products

NH

NH

O

R R 2 Products


Diamination – Initial Results

Conditions are modified Wacker conditions- Regioselectivity of first complexation- Unsymmetric ureas (solubility also a problem)- needs chloride Pd pre-catalyst


Question Time – Wacker Oxidation

RPdCl2, CuCl2

H2O, O2R

O


Diamination – Further Results

- Benzoquinone (method A) is superior oxidant- best for symmetric dienes


Enatioselective Diboronation of Olefins

• Works for terminal & di-substiuted alkene, not tri subst• Works best for trans alkenes • Tolerates protected alcohols

Morken et al, JACS 2003, 8702; JOC 2005 9538

50-98%50-96% ee


Enatioselective Diboronation of Olefins

Morken et al, JOC 2005 9538


Carbohyroxyltion of Olefins

Morken et al, Org. Lett. 2004, 131

One-pot diboronation-Suzuki cross coupling


Diboronation Mechanism


Regioselective Aminoacetoxylation

Stahl et al, JACS 2006, 7179

• Racemic addition• Requires adjacent ether in substrate• Interesting IIII reagent oxidises Pd-C bond…


Regioselective Aminoacetoxylation


Hydroxysulfenation

AcOSR


Hydroxysulfenation

• R1 = Ar, alk• R1=R2 = c-hex, Ar • R3 = Ar, Cy• Complete diastereoselectivity• can also replace S-Ar with Si-iPr, SePh & SnBu

Taniguchi, JACS 2006, 7876


Hydroxysulfenation

sean parris, olefin bisfunctionalisation the ad catalytic cycle chem. rev. 1994, 94, 2483-2547

Documents

sean parris

ee slide

catalyst slide

p1095 slide

phal ad slide

secondary cycle slide

cyclic system slide

attractive area slide