the ad catalytic cycle
Download
Skip this Video
Download Presentation
The AD Catalytic Cycle

Loading in 2 Seconds...

play fullscreen
1 / 32

The AD Catalytic Cycle - PowerPoint PPT Presentation


  • 55 Views
  • Uploaded on

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”.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about ' The AD Catalytic Cycle' - kiara-nieves


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
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

ad