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Sean Parris, Olefin Bisfunctionalisation The AD Catalytic Cycle Chem. Rev. 1994, 94, 2483-2547.

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Presentation on theme: "Sean Parris, Olefin Bisfunctionalisation The AD Catalytic Cycle Chem. Rev. 1994, 94, 2483-2547."— Presentation transcript:

1 Sean Parris, Olefin Bisfunctionalisation The AD Catalytic Cycle Chem. Rev. 1994, 94,

2 Sean Parris, Olefin Bisfunctionalisation Shutting Down the Secondary Cycle

3 Sean Parris, Olefin Bisfunctionalisation The Cinchona Alkaloids (DHQ) 2 PHAL “AD-  ”

4 Sean Parris, Olefin Bisfunctionalisation The AD-Mix Mnemonic Works best for: trans alkenes terminal olefins quite bad with aromatic ring to sit in “attractive area”

5 Sean Parris, Olefin Bisfunctionalisation Which Ligand System?

6 Sean Parris, Olefin Bisfunctionalisation Racemic Dihydroxylation – Beyond Upjohn Upjohn (NMO, OsO 4 ) can be slow & prone to over-oxidation J. Eames, H. Mitchell, A. Nelson, P. O’Brien, S. Warren, P. Wyatt, Perkin , p1095

7 Sean Parris, Olefin Bisfunctionalisation Sharpless Asymmetric Aminohydroxylation (AA)

8 Sean Parris, Olefin Bisfunctionalisation Sharpless et al. Angew. Int Sharpless Asymmetric Aminohydroxylation (AA)

9 Sean Parris, Olefin Bisfunctionalisation AA –Mechanism Review: McLeod et al, Perkin 1, 2002, 2733

10 Sean Parris, Olefin Bisfunctionalisation AA – Standard Conditions? Review: P. O’Brien, Angew. Int, 1999, 326

11 Sean Parris, Olefin Bisfunctionalisation Competing Dihydroxylation First turnover of catalyse is AD Can reduce AD with slow addition of substrate

12 Sean Parris, Olefin Bisfunctionalisation AA – Best Substrates Cinnamates best using (DHQ) 2 PHAL (as drawn) (DHQ) 2 AQN (regioisomer) ,  -unsat’d (DHQ) 2 PHAL (as drawn) effect ligand unknown

13 Sean Parris, Olefin Bisfunctionalisation 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!

14 Sean Parris, Olefin Bisfunctionalisation Sharpless Aminohydroxylation – Further Work  ,  -unsat’d amides & carboxylic acids found to be good substrates for a racemic AH (Angew. 1997, p2751; Angew ) 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)

15 Sean Parris, Olefin Bisfunctionalisation Other Aminhydroxylations - TA Tethered Aminohydroxylation (TA) Donohoe et al, JACS 2002, Stereochemistry comes from allylic alcohol Stereoinduction requires cyclic system

16 Sean Parris, Olefin Bisfunctionalisation Tethered Aminohydroxylation

17 Sean Parris, Olefin Bisfunctionalisation Tethered Aminohydroxylation - Mechanism

18 Sean Parris, Olefin Bisfunctionalisation Diamination to Conjugated Dienes (1) disfavour 3 (2) favour Nu addn to give diamine (3) amine souce that won’t react with other species

19 Sean Parris, Olefin Bisfunctionalisation Question Time – Predict the Products

20 Sean Parris, Olefin Bisfunctionalisation Diamination – Initial Results Conditions are modified Wacker conditions - Regioselectivity of first complexation - Unsymmetric ureas (solubility also a problem) - needs chloride Pd pre-catalyst

21 Sean Parris, Olefin Bisfunctionalisation Question Time – Wacker Oxidation

22 Sean Parris, Olefin Bisfunctionalisation Diamination – Further Results - Benzoquinone (method A) is superior oxidant - best for symmetric dienes

23 Sean Parris, Olefin Bisfunctionalisation 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 % 50-96% ee

24 Sean Parris, Olefin Bisfunctionalisation Enatioselective Diboronation of Olefins Morken et al, JOC

25 Sean Parris, Olefin Bisfunctionalisation Carbohyroxyltion of Olefins Morken et al, Org. Lett. 2004, 131 One-pot diboronation-Suzuki cross coupling

26 Sean Parris, Olefin Bisfunctionalisation Diboronation Mechanism

27 Sean Parris, Olefin Bisfunctionalisation Regioselective Aminoacetoxylation Stahl et al, JACS 2006, 7179 Racemic addition Requires adjacent ether in substrate Interesting I III reagent oxidises Pd-C bond…

28 Sean Parris, Olefin Bisfunctionalisation Regioselective Aminoacetoxylation

29 Sean Parris, Olefin Bisfunctionalisation Hydroxysulfenation

30 Sean Parris, Olefin Bisfunctionalisation 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

31 Sean Parris, Olefin Bisfunctionalisation Hydroxysulfenation

32 Sean Parris, Olefin Bisfunctionalisation Hydroxysulfenation


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