Stereoselective Oxidation and Reduction Reactions

1
Stereoselective Oxidationand Reduction Reactions
Dr Simon Woodward School of Chemistry, University
of Nottingham
2
Oxidation Reactions

• Epoxidation
• Epoxide opening
• Dihydroxylation
• Aminohydroxylation
• Alcohol oxidation

Click Chemistry Diverse Chemical Function from
a Few Good Reactions Kolb, Finn, Sharpless,
Angew. Chem. Int. Ed. 2001, 40, 2004.
3
Sharpless Asymmetric Epoxidation of Allylic
Alcohols
Review Katsuki and Martin, Org. React., 1996,
48, 1.
tBuOOH, Ti(OiPr)4, DET, CH2Cl2, 4Å MS
Sharpless, J. Am. Chem. Soc., 1987, 109, 5765
. Mechanism J. Am. Chem. Soc., 1991, 113, 106
and 113.

• Hydroxamic acid ligands for Vanadium-catalysed
  asymmetric epoxidation of allylic alcohols
• Yamamoto, J. Am. Chem. Soc. 2000, 122, 10452.

4
Chiral Mn(salen) Catalysts Overview
Review Katsuki Coord. Chem. Rev. 1995, 140, 189.
Stoichiometric co-oxidants Usually aq. NaOCl,
CH2Cl2 mCPBA / NMO (low temperature)
Preparation of catalyst Organic Syntheses, 1998,
75, 1. Polymer supported catalyst e.g. Janda,
J. Am. Chem. Soc., 2000, 122, 6929. Cis-Disubstit
uted alkenes J. Am. Chem. Soc. 1991, 113,
7063. Trisubstituted alkenes J. Org. Chem. 1994,
59, 4378. Tetrasubstituted alkenes Tetrahedron
Lett. 1995, 36, 5123. Cinnamate esters
Tetrahedron 1994, 50, 4323.

• Poor enantioselectivities for trans-disubstituted
  and terminal alkenes
• (but see Katsuki, Synlett, 2000, 1557)
• Via radical intermediate, so stereospecificity
  with respect to alkene geometry sometimes eroded.
  
• Can use to make trans-epoxides from cis-alkenes
  Jacobsen, J. Am. Chem. Soc. 1994, 116, 6937.
• Asymmetric epoxidation of E-alkenes using
  Cr(salens) Gilheany, Org. Lett. 2001, 3, 663,
  and refs. therein

5
Dioxiranes
Electrophilic oxidants, but successful for
epoxidation of electron poor alkenes e.g.
Baumstark, J. Org. Chem., 1993, 58, 7615.
Isolation of dioxiranes neutral, anhydrous
oxidants Preparation of dimethyldioxirane (DMDO)
solutions Adam, Chem. Ber., 1991, 124,
2377. More concentrated, acetone free
solutions Messeguer, Tetrahedron Lett., 1996,
37, 3585.
In situ dioxirane formation Biphasic, CH2Cl2 /
H2O Denmark, J. Org. Chem., 1995, 60,
1391. Monophasic, CH3CN / H2O Yang, J. Org.
Chem., 1995, 60, 3887. In situ DMDO prep. Shi,
J. Org. Chem., 1998, 63, 6425. Trifluoroacetone
H2O2 Shi, J. Org. Chem., 2000, 65, 8808.
6
Chiral Dioxiranes Asymmetric Epoxidation of
trans-Alkenes
Shi, J. Am. Chem. Soc. 1997, 119, 11224.
Review Shi, Synthesis, 2000, 1979.

• Preparation 2 steps from D-fructose (enantiomer
  available in 5 steps from L-sorbose)
• Excellent enantioselectivities for epoxidation
  of trisubstituted and trans-disubstituted alkenes
• Poor ee for cis- and terminal alkenes
• Ketone decomposes by Baeyer-Villiger reaction -
  cannot be recycled. High pH conditions required.

Other substrate typesConjugated dienes J. Org.
Chem. 1998, 63, 2948 Enynes Tetrahedron Lett.
1998, 39, 4425. Modified catalyst for
cis-alkenes J. Am. Chem. Soc. 2000, 122,
11551. Terminal alkenes Org. Lett., 2001, 3,
1929. Stable catalystsArmstrong, Chem.
Commun. 1998, 625 Tetrahedron Asymmetry, 2000,
11, 2057. Shi, Org. Lett. 2001, 3, 715.
7
Oxidation of silyl enol ethers
Shi, Tetrahedron Lett. 1998, 39, 7819
Other methods for asymmetric oxidation of silyl
enol ethers Chiral Mn(salens) Thornton, Chem.
Commun. 1992, 172 Adam, Tetrahedron Lett. 1996,
37, 6531, and refs. therein. Chiral oxaziridines
Review Davis, Chem. Rev., 1992, 92,
919. Asymmetric dihydroxylation J. Org. Chem.
1992, 57, 5067.
8
Hydrolytic Kinetic Resolution
Jacobsen, Science 1997, 277, 936. Acc. Chem.
Res. 2000, 33, 421.

• Catalyst can be recycled (AcOH, air)

• Easily-synthesised oligomeric Co(salen)
  catalysts are highly active for epoxide opening
• by water, alcohols and phenols J. Am. Chem.
  Soc. 2001, 123, 2687.

9
Asymmetric Epoxidation of Electron-Deficient
Alkenes
Review M.J. Porter and J. Skidmore, Chem.
Commun., 2000, 1215.

• Polyleucine, H2O2, base e.g. Tetrahedron Lett.,
  2001, 42, 3741.
• Reviews Tetrahedron Asymmetry 1997, 8, 3163
  1998, 9, 1457.
• Catalytic Mg peroxides (tBuOOH, cat. Bu2Mg, cat.
  diethyl tartrate) R1, R2Ph
• Jackson, Angew. Chem., Int. Ed. Engl. 1997, 36,
  410.
• Chiral phase-transfer catalysts (R2 can be
  alkyl) Lygo, Tetrahedron, 1999, 55, 6289
• Tetrahedron Lett. 2001, 42, 1343.
• Lanthanide catalysis (BINOL, La(OiPr)3 or
  Yb(OiPr)3, 4Å MS, tBuOOH)
• R1Ph, iPr or Me R2Ph, iPr, Ph(CH2)2 or Me.
• La-BINOL-Ph3AsO -mechanistic studies J. Am.
  Chem. Soc., 2001, 123, 2725.
• Chiral hydroperoxides, KOH, CH3CN Adam, J. Am.
  Chem. Soc., 2000, 122, 5654.
• Stoichiometric zinc alkylperoxides (O2, Et2Zn,
  ROH) R1Ph or tBu, R2alkyl or aryl
• Enders, Angew. Chem. Int. Ed. Engl. 1996, 35,
  1725 Liebigs Ann. Chem. 1997, 1101
• Chiral dioxiranes e.g. Tetrahedron Asymmetry,
  2001, 12, 1113.

10
Alkene Dihydroxylation

• Catalytic systems
• NMO / acetone / H2O (Upjohn procedure)
  Tetrahedron Lett. 1976, 23, 1973.
• Cat. Me3NO2H2O, CH2Cl2 Poli, Tetrahedron Lett.
  1989, 30, 7385.
• K3Fe(CN)6, K2CO3, tBuOH / H2O Minato, Yamamoto,
  Tsuji, J. Org. Chem. 1990, 55, 766.
• NMO, PhB(OH)2, CH2Cl2 Narasaka, Chem. Lett.
  1988, 1721.
• - Diol trapped as boronate ester - useful if
  diol is unstable or highly water soluble
• Selenoxides as co-oxidants Krief, Synlett,
  2001, 501.
• H2O2, cat. flavin, cat. N-methylmorpholine
  Backvall, J. Am. Chem. Soc. 1999, 121, 10424
• J. Am. Chem. Soc. 2001, 123, 1365.
• H2O2, cat. V(O)(acac)2, NMM, acetone/water
  Backvall, Tetrahedron Lett., 2001, 42, 2569.
• O2, K2OsO2(OH)4, tBuOH / H2O
• Beller, Angew. Chem. Int. Ed. 1999, 38, 3026
  J. Am. Chem. Soc. 2000, 122, 10289.

11
Directed Dihydroxylations
Kishi rule - dihydroxylation occurs anti- to
oxygen functionality. Review Cha, Chem. Rev.
1995, 95, 1761.
Hydroxyl-directed dihydroxylation Donohoe,
Tetrahedron Lett. 1997, 38, 5027.

• Bidentate ligand required

• Dihydroxylation directed by trichloroacetamides
  Donohoe, J. Org. Chem. 1999, 64, 2980.
• Catalytic directed dihydroxylation of cyclic
  trichloroacetamides Donohoe, Tetrahedron Lett.
  2000, 41, 4701.
• Syn-selective dihydroxylation of acyclic allylic
  alcohols Donohoe, Tetrahedron Lett. 1999, 40,
  6881.

12
Sharpless Asymmetric Dihydroxylation
Review Sharpless, Chem. Rev. 1994, 94, 2483.
DHQD series
DHQD dihydroquinidine DHQ dihydroquinine
"pseudoenantiomers"
DHQ series
13
Sharpless AD Recent Developments

• Improved ligands
• Pyrimidine (PYR) spacer for sterically congested
  / terminal alkenes J.Org. Chem. 1993, 58, 3785.
• Anthraquinone (AQN) spacer gives better results
  for almost all alkenes having only aliphatic
  substituents
• Angew. Chem. Int. Ed. Engl. 1996, 35, 448.

Mechanism

• Comparison of theoretical and experimental
  kinetic isotope effects supports 32-mechanism
• Sharpless, Houk et al. J. Am. Chem. Soc. 1997,
  119, 9907.

Origins of asymmetric induction Sharpless J.
Am. Chem. Soc. 1997, 119, 1840. Corey (enzyme
like binding pocket) J. Am. Chem. Soc. 1996,
118, 319 11038.
Polymer supported chiral ligands Review
Synlett, 1999, 1181. Crudden, Org. Lett. 2001, 3,
2325. Bolm, Synlett, 2001, 93 (AQN-ligands).
Polymer supported Os-catalyst Kobayashi, J. Am.
Chem. Soc. 1999, 121, 11229. Org. Lett. 2001, 3,
2649. Importance of pH control improved rates
for internal olefins at pH 12 (no MeSO2NH2)
higher ee for terminal olefins at pH 10 Beller,
Tetrahedron Lett. 2000, 41, 8083.
14
Aminohydroxylation
Review OBrien, Angew. Chem., Int. Ed. Engl.
1999, 38, 326.

• DHQD-ligand series generally provide opposite
  enantiomer.
• Effect of substrate structure on
  regioselectivity Janda, Chem. Eur. J. 1999, 5,
  1565.

Cinnamates

• Aryl esters (and AQN-ligands) give opposite
  regioselectivity! Panek, Org. Lett. 1999, 1,
  1949.
• Can be run at higher concentration in presence
  of acetamide to suppress diol formation
• Wuts, Org. Lett. 2000, 2, 2667.

Styrenes, Aryl alkenes (XTs, CBz, Boc, Teoc)

• Altering ligand spacer, solvent can reverse
  regioselectivity without decreasing ee!

15
Recent Developments in Asymmetric
Aminohydroxylation

• Amino-substituted heterocycles as nitrogen
  sources Sharpless, Angew. Chem. Int. Ed. Engl.
  1999, 38, 1080.
• Adenine derivatives as N-source Sharpless,
  Tetrahedron Lett. 1998, 39, 7669.

• N-bromo-N-lithio salts of primary carboxamides
  as N-source Sharpless, Org. Lett. 2000, 2, 2221.
• Unsaturated phosphonates as substrates
  Sharpless, J. Org. Chem., 1999, 64, 8379.

16
Pd-Catalysed Oxidative Kinetic Resolution of
Secondary Alcohols with O2
Sigman, J. Am. Chem. Soc. 2001, 123, 7475.
Stoltz, J. Am. Chem. Soc. 2001, 123, 7725.
17
Reduction Reactions
Asymmetric reduction of alkenes, ketones,
imines.

• Hydrogenation
• Transfer hydrogenation
• Boranes
• Hydride reagents
• Hydrosilylation

18
Monsanto synthesis of L-DOPA
19
Rh(I)-BINAP Complexes
Noyori, J. Am. Chem. Soc. 1980, 102, 7932.
Ru BINAP complexes are more general work for
e.g. simple acrylic acids. Mechanistically
distinct Tetrahedron Lett. 1990, 31, 7189.
20
Rh(I)-diphosphole Complexes
Review Burk, Acc. Chem. Res. 2000, 33, 363

• sense of enantioselectivity independent of
  acrylamide geometry

21
Monodentate ligands
MonoPhos deVries, Feringa, J. Am. Chem. Soc.
2000, 122, 11539. Ligand A Reetz, Angew. Chem.
Int. Ed. 2000, 39, 3889. Review Angew. Chem.
Int. Ed. 2001, 40, 1197.
22
Asymmetric Hydrogenation of Functionalised Ketones
Ru BINAP J. Am. Chem. Soc. 1987, 109, 5856 J.
Am. Chem. Soc. 1988, 110, 629. Ru BPE J. Am.
Chem. Soc. 1995, 115, 4423. Review Ager,
Tetrahedron Asymm. 1997, 8, 3327.
23
Catalytic asymmetric hydrogenation of aminoketones
Noyori, J. Am. Chem. Soc. 2000, 122, 6510.

• Mixed Ru bisphosphine/diamine complexes afford
  much improved turnover numbers

• Basic conditions allow dynamic kinetic
  resolution

Also for reduction of unfunctionalised ketones.
Review Noyori, Angew. Chem., Int. Ed., 2001, 40,
40.
24
Asymmetric Transfer Hydrogenation of Ketones
Reduction with the aid of a hydrogen donor in the
presence of a catalyst Reviews Wills,
Tetrahedron Asymmetry, 1999, 10, 2045 Noyori,
Acc. Chem. Res. 1997, 30, 97.
Aminoalcohols as ligands
Arylalkylketones with electron rich aryl groups
and benzocycloalkanones suffer from reversibility
and give lower eebut aminoalcohols are
generally not compatible with the irreversible
hydride donor formic acid
25
Monotosylated diamines formic acid-tolerant
ligands for transfer hydrogenation
- monotosylated diamines give slightly less
reactive catalysts than the amino alcohols but
have proven to be a more useful ligand system
for ruthenium based transfer hydrogenations since
compatibility with the formic acid system
allows efficient reduction even in readily
reversible systems
26
Ketone Reduction Catalyzed by Oxazaborolidines
Review Angew Chem. Int. Ed. 1998, 37, 1986
27
Polymer-supported amino alcohol and in situ
generation of borane
Angew. Chem. Int. Ed., 2001, 40,1109
28
Asymmetric reduction of ketones stoichiometric
aluminium hydrides
Noyori, J. Am. Chem. Soc., 1984, 106, 6709, 6717
29
A catalytic binapthyl-substituted hydride source
based on hard-soft principles
Woodward, Angew. Chem., Int. Ed. Engl., 1999, 38,
335 Chem. Eur. J. 2000, 6, 3586.
- replacing 'hard' aluminium by 'soft' gallium,
the intermediate 'hard' alkoxide can be
transferred to the 'hard' borane
stoichiometric co-reductant, allowing catalytic
turnover
30
Hydrosilylation of imines/ketones an alternative
to hydrogenative reduction
Organometallics, 1991, 10, 560TetrahedronAsymm.,
1991, 2, 919
31
Asymmetric hydrosilylation of ketones and imines
using cheap siloxanes
PMHS poly(methylhydrosiloxane)
J. Am. Chem. Soc., 1999, 121, 5640
(ketone) Angew. Chem., Int. Ed. Engl., 1998, 37,
1103, Org. Lett., 2000, 2, 713 (imine)
32
Catalytic asymmetric hydrosilylation of
enones/enoates
Buchwald, J. Am. Chem. Soc., 1999, 121, 9473 J.
Am. Chem. Soc., 2000, 122, 6797