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The AD Catalytic Cycle. Chem. Rev. 1994, 94, 2483-2547. Shutting Down the Secondary Cycle. The Cinchona Alkaloids. (DHQ) 2 PHAL “AD- a ”. The AD-Mix Mnemonic. Works best for: trans alkenes terminal olefins quite bad with aromatic ring to sit in “attractive area”.

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The ad catalytic cycle
The AD Catalytic Cycle

Chem. Rev. 1994, 94, 2483-2547

Sean Parris, Olefin Bisfunctionalisation


Shutting down the secondary cycle
Shutting Down the Secondary Cycle

Sean Parris, Olefin Bisfunctionalisation


The cinchona alkaloids
The Cinchona Alkaloids

(DHQ)2PHAL

“AD-a”

Sean Parris, Olefin Bisfunctionalisation


The ad mix mnemonic
The AD-Mix Mnemonic

  • Works best for:

  • trans alkenes

  • terminal olefins quite bad

  • with aromatic ring to sit in

  • “attractive area”

Sean Parris, Olefin Bisfunctionalisation


Which ligand system
Which Ligand System?

Sean Parris, Olefin Bisfunctionalisation


Racemic dihydroxylation beyond upjohn
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

Sean Parris, Olefin Bisfunctionalisation


Sharpless asymmetric aminohydroxylation aa
Sharpless Asymmetric Aminohydroxylation (AA)

Sean Parris, Olefin Bisfunctionalisation


Sharpless asymmetric aminohydroxylation aa1
Sharpless Asymmetric Aminohydroxylation (AA)

Sharpless et al. Angew. Int.1997 438

Sean Parris, Olefin Bisfunctionalisation


Aa mechanism
AA –Mechanism

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

Sean Parris, Olefin Bisfunctionalisation


Aa standard conditions
AA – Standard Conditions?

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

Sean Parris, Olefin Bisfunctionalisation


Competing dihydroxylation
Competing Dihydroxylation

  • First turnover of catalyse is AD

  • Can reduce AD with slow addition of substrate

Sean Parris, Olefin Bisfunctionalisation


Aa best substrates
AA – Best Substrates

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

(DHQ)2AQN (regioisomer)

a,b-unsat’d

(DHQ)2PHAL (as drawn)

effect ligand unknown

Sean Parris, Olefin Bisfunctionalisation


Aa more substrates
AA – More Substrates

  • Styrenes, a,b-unsat’d esters & vinyl arenes only work with acetamide & carbamate

  • Other egs where DHQ vs DHQD give regioisomers in similar ee of opposite stereoinduction!

Sean Parris, Olefin Bisfunctionalisation


Sharpless aminohydroxylation further work
Sharpless Aminohydroxylation – Further Work

  • a,b-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)

Sean Parris, Olefin Bisfunctionalisation


Other aminhydroxylations ta
Other Aminhydroxylations - TA

Tethered Aminohydroxylation (TA)

  • Stereochemistry comes from allylic alcohol

  • Stereoinduction requires cyclic system

Donohoe et al, JACS2002, 12934

Sean Parris, Olefin Bisfunctionalisation


Tethered aminohydroxylation
Tethered Aminohydroxylation

Sean Parris, Olefin Bisfunctionalisation


Tethered aminohydroxylation mechanism
Tethered Aminohydroxylation - Mechanism

Sean Parris, Olefin Bisfunctionalisation


Diamination to conjugated dienes
Diamination to Conjugated Dienes

(1) disfavour 3 (2) favour Nu addn to give diamine

(3) amine souce that won’t react with other species

Sean Parris, Olefin Bisfunctionalisation


Question time predict the products
Question Time – Predict the Products

Sean Parris, Olefin Bisfunctionalisation


Diamination initial results
Diamination – Initial Results

  • Conditions are modified Wacker conditions

  • - Regioselectivity of first complexation

  • Unsymmetric ureas (solubility also a problem)

  • needs chloride Pd pre-catalyst

Sean Parris, Olefin Bisfunctionalisation


Question time wacker oxidation
Question Time – Wacker Oxidation

Sean Parris, Olefin Bisfunctionalisation


Diamination further results
Diamination – Further Results

  • Benzoquinone (method A) is superior oxidant

  • best for symmetric dienes

Sean Parris, Olefin Bisfunctionalisation


Enatioselective diboronation of olefins
Enatioselective Diboronation of Olefins

50-98%

50-96% ee

  • Works for terminal & di-substiuted alkene, not tri subst

  • Works best for trans alkenes

  • Tolerates protected alcohols

Morken et al, JACS2003, 8702; JOC 2005 9538

Sean Parris, Olefin Bisfunctionalisation


Enatioselective diboronation of olefins1
Enatioselective Diboronation of Olefins

Morken et al, JOC 2005 9538

Sean Parris, Olefin Bisfunctionalisation


Carbohyroxyltion of olefins
Carbohyroxyltion of Olefins

One-pot diboronation-Suzuki cross coupling

Morken et al, Org. Lett. 2004,131

Sean Parris, Olefin Bisfunctionalisation


Diboronation mechanism
Diboronation Mechanism

Sean Parris, Olefin Bisfunctionalisation


Regioselective aminoacetoxylation
Regioselective Aminoacetoxylation

  • Racemic addition

  • Requires adjacent ether in substrate

  • Interesting IIII reagent oxidises Pd-C bond…

Stahl et al, JACS2006, 7179

Sean Parris, Olefin Bisfunctionalisation


Regioselective aminoacetoxylation1
Regioselective Aminoacetoxylation

Sean Parris, Olefin Bisfunctionalisation


Hydroxysulfenation
Hydroxysulfenation

Sean Parris, Olefin Bisfunctionalisation


Hydroxysulfenation1
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

Sean Parris, Olefin Bisfunctionalisation


Hydroxysulfenation2
Hydroxysulfenation

Sean Parris, Olefin Bisfunctionalisation


Hydroxysulfenation3
Hydroxysulfenation

Sean Parris, Olefin Bisfunctionalisation


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