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

Sean Parris, Olefin Bisfunctionalisation Shutting Down the Secondary Cycle

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

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”

Sean Parris, Olefin Bisfunctionalisation Which Ligand System?

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

Sean Parris, Olefin Bisfunctionalisation Sharpless Asymmetric Aminohydroxylation (AA)

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

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

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

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

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

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!

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)

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

Sean Parris, Olefin Bisfunctionalisation Tethered Aminohydroxylation

Sean Parris, Olefin Bisfunctionalisation Tethered Aminohydroxylation - Mechanism

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

Sean Parris, Olefin Bisfunctionalisation Question Time – Predict the Products

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

Sean Parris, Olefin Bisfunctionalisation Question Time – Wacker Oxidation

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

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

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

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

Sean Parris, Olefin Bisfunctionalisation Diboronation Mechanism

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…

Sean Parris, Olefin Bisfunctionalisation Regioselective Aminoacetoxylation

Sean Parris, Olefin Bisfunctionalisation Hydroxysulfenation

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

Sean Parris, Olefin Bisfunctionalisation Hydroxysulfenation

Sean Parris, Olefin Bisfunctionalisation Hydroxysulfenation