Stereoselective Oxidation and Reduction Reactions Dr Simon Woodward School of Chemistry, University of Nottingham
Dec 19, 2015
Stereoselective Oxidationand Reduction Reactions
Dr Simon WoodwardSchool of Chemistry, University of Nottingham
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.
Sharpless Asymmetric Epoxidation of Allylic Alcohols
Review: Katsuki and Martin, Org. React., 1996, 48, 1.
OH
R1R2
R3
(-)-DET "O"
(+)-DET "O"
Sharpless, J. Am. Chem. Soc., 1987, 109, 5765 .Mechanism: J. Am. Chem. Soc., 1991, 113, 106 and 113.
• tBuOOH, Ti(OiPr)4, DET, CH2Cl2, 4Å MS
• Hydroxamic acid ligands for Vanadium-catalysed asymmetric epoxidation of allylic alcohols: Yamamoto, J. Am. Chem. Soc. 2000, 122, 10452.
Chiral Mn(salen) Catalysts: Overview
N N
O OtBu tBu
tButBu
Mn
Cl
H H
Stoichiometric co-oxidants:Usually aq. NaOCl, CH2Cl2mCPBA / 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-Disubstituted 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.
Review: Katsuki Coord. Chem. Rev. 1995, 140, 189.
• 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
PhPh
O
0.04eq. (R,R)-Mn(salen)Cl
NaOCl, pH 11.3CH2Cl2, 4ºC
84% yield92% ee
Dioxiranes
R1 R1
O Oxone® (KHSO5)
R1 R2
OO
Base
Isolation of dioxiranes: neutral, anhydrous oxidantsPreparation of dimethyldioxirane (DMDO) solutions: Adam, Chem. Ber., 1991, 124, 2377.More concentrated, “acetone free” solutions: Messeguer, Tetrahedron Lett., 1996, 37, 3585.
• Electrophilic oxidants, but successful for epoxidation of electron poor alkenes: e.g. Baumstark, J. Org. Chem., 1993, 58, 7615.
In situ dioxirane formationBiphasic, 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.
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.
O
O
O
OO
O
PhCH3
30 mol% ketone
Oxone, K2CO3CH3CN, 0ºC
pH 10.5 buffer
PhCH3
O
93% yield; 92% ee
(Use of H2O2 as primary oxidant: Tetrahedron Lett., 1999, 40, 8721;Tetrahedron, 2001, 57, 5213.)
O
OO
OO
OO
RH
R
Other substrate types:Conjugated dienes: J. Org. Chem. 1998, 63, 2948Enynes: 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 catalysts:Armstrong, Chem. Commun. 1998, 625; Tetrahedron: Asymmetry, 2000, 11, 2057. Shi, Org. Lett. 2001, 3, 715.
Oxidation of silyl enol ethers
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.
Shi, Tetrahedron Lett. 1998, 39, 7819:
Ph
OTBDMS
Ph
OCat. ketone, Oxone
CH3CN, aq. buffer
OH
80% yield90% ee
O OO
O
OO
Ketone =
OR ORO
R=Ac: 59% yield, 74% eeR=Bz: 82% yield, 93% ee
O
OBz
O
OBz
pTsOHsilica gelor YbCl3or AlMe3R=Bz
90% ee 87-91% ee
ShiJ. Am. Chem. Soc. 1999, 121, 4080.
Hydrolytic Kinetic Resolution
Jacobsen, Science 1997, 277, 936. Acc. Chem. Res. 2000, 33, 421.
O1. 0.2 mol% (salen)*Co(III)(OAc) 0.55 eq. H2O, rt, 12 hr
2. Distillation
OOH
OH
> 98% ee(44% yield)
> 98% ee(50% yield)
+
• 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.
Asymmetric Epoxidation of Electron-Deficient Alkenes
R1 R2
O
R1 R2
OO
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, R2=Ph 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): R1=Ph, iPr or Me; R2=Ph, 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, R*OH): R1=Ph or tBu, R2=alkyl 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.
Alkene Dihydroxylation
R1
R3
R2
R4 R3 R4
OH OHR1 R2
OsO4
R3 R4
O OR1 R2
OsO O
Catalytic systems:• NMO / acetone / H2O (Upjohn procedure): Tetrahedron Lett. 1976, 23, 1973.
• Cat. Me3NO•2H2O, 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, K2[OsO2(OH)4], tBuOH / H2O: Beller, Angew. Chem. Int. Ed. 1999, 38, 3026; J. Am. Chem. Soc. 2000, 122, 10289. Wirth, Angew. Chem. Int. Ed. 2000, 39, 334.
Fe-catalysed asymmetric dihydroxylation: Que, J. Am. Chem. Soc. 2001, 123, 6722.
Directed Dihydroxylations
“Kishi rule” - dihydroxylation occurs anti- to oxygen functionality.Review: Cha, Chem. Rev. 1995, 95, 1761.
OH
But
OH
But
OH
But
OsO4, NMO, acetone / H2OOsO4, TMEDA, CH2Cl2, -78ºC
+
OH
OH
OH
OH
anti syn
7:11:24
O
H
But
OsO
N O
O
N
O
OH OH
OsO4, TMEDA
CH2Cl2, -78ºCHO
OH
Regioselectivity > 25:1
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.
Sharpless Asymmetric Dihydroxylation
NNO
N
OMe
N
O
N
MeO
H
EtN
Et
H
(DHQD)2-PHAL
AD-Mix:K2OsO2(OH)4, ligand,
K3Fe(CN)6, K2CO3
Review: Sharpless, Chem. Rev. 1994, 94, 2483.
RM
H
RS
RL
"HO" "OH"
"HO" "OH"
-face
-face
slightly hindered
very!!!!!hindered
attractive area - good for aromatic
and alkyl substituents
DHQD= dihydroquinidineDHQ= dihydroquinine "pseudoenantiomers"
DHQ series
DHQD series
Sharpless AD: Recent DevelopmentsImproved 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 [3+2]-mechanism Sharpless, Houk et al. J. Am. Chem. Soc. 1997, 119, 9907.
OOs
O
O O
[3+2]
Os O
OO
OOs O
OO
O[2+2]
OOs
O
O O
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.
AminohydroxylationReview: O’Brien, Angew. Chem., Int. Ed. Engl. 1999, 38, 326.
R1
R2
XNClNa (X=Ts, Ms, CBz, Boc, Teoc)OR XNBrLi (X=Ac)
4 mol% K2OsO2(OH)25 mol% (DHQ)2PHAL
1:1 ROH:H2O
R1
R2R1
R2
NHX
OH
OH
NHX
+
• DHQD-ligand series generally provide opposite enantiomer.• Effect of substrate structure on regioselectivity: Janda, Chem. Eur. J. 1999, 5, 1565.
PhCO2Me
PhCO2Me
NHX
OH
X=Ts: 60% yield, 82% eeX=Cbz: 65% yield, 94% ee
Cinnamates:
Styrenes, Aryl alkenes (X=Ts, CBz, Boc, Teoc):
OH
NHBoc
70% yield98% ee
• Altering ligand spacer, solvent can reverse regioselectivity without decreasing ee!
• 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.
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 N
NH2
1. tBuOCl, EtOH, 0ºC
2. Aq. NaOH, 0ºCN N
N-Cl Na+
PhPh
5% K2OsO2(OH)46% (DHQ)2PHAL
rt
PhPh
OH
NH
N
N
45% yield97% ee
• 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.
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.
OH O OH5 mol% Pd(nbd)Cl220 mol% (-)-sparteine
3Å MS, 1 atm O2PhCH3, 80ºC
+
(±)
S = kfast/kslow = 47.1
55% conversion5.0 g 2.7 g 2.2 g, 99% ee
NaBH4, MeOH99%
Reduction Reactions
• Hydrogenation
• Transfer hydrogenation
• Boranes
• Hydride reagents
• Hydrosilylation
Asymmetric reduction of alkenes, ketones, imines…….
Monsanto synthesis of L-DOPA
CO2Me
NHAc
CO2Me
NHAc0.1% [(R,R)-(dipamp)Rh(COD)]+BF4
3 atm H2, 50°C, H2O / iPrOH
MeO OMe MeO OMe
CO2-
NH3+
HO OH
HBr
L-DOPA(anti-Parkinson's)
OMe
P P
MeO
Ph
Ph
= (R,R)-dipamp
94% ee
Rh(I)-BINAP Complexes
(S)-BINAP
PPh2
PPh2
[(S)-(BINAP)Rh(nbd)]+ClO4-
Ph NHAc
CO2R
Ph NHAc
CO2R
H2, MeOHR=Me 98%, 93% eeR=H 97%, 100% ee
[(S)-(BINAP)Rh(nbd)]+ClO4-
NHAc
CO2H
Ph NHAc
CO2H
H2, MeOH93%, 87% ee
Ph
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.
Rh(I)-diphosphole Complexes
P P
R
RR
R
P
P
R
R
R
RR = Me, Et, Pr
(R,R)-DuPHOS(R,R)-BPE
Review: Burk, Acc. Chem. Res. 2000, 33, 363
0.05% [Rh(R,R-nPr-DuPHOS)(COD)]+TfO-
R2 NHAc
CO2Me
NHAc
CO2Me
2 atm H2, MeOH
R1=H, R2=MeR1=Me, R2=H
R1
99.6% ee99.4% ee
• sense of enantioselectivity independent of acrylamide geometry
Monodentate ligands
O
OPNMe2
O
OP O
(S)-MonoPhos
Ligand A
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.
CO2Me
CO2Me
CO2Me
CO2Men% [Rh(cod)2]BF4
2n% ligand, CH2Cl2
(S)-MonophosLigand A
n=5, 1atm H2, 0°Cn=0.1, 1.3 bar H2, rt
94.4% ee99.6% ee
NHAc
CO2Me
NHAc
CO2Men% [Rh(cod)2]BF4
2n% ligand, CH2Cl2
(S)-MonophosLigand A
n=5, 1atm H2, rtn=0.1, 1.3 bar H2, rt
99% ee95.5% ee
Asymmetric Hydrogenation of Functionalised Ketones
OXR
Ru
(S)-BINAP
(R)-BINAP
O
RX
RX
OH
R
MePhMeMe
(CH2)2CH=Me2CH2Cl
Me
X
NMe2NMe2CH2OHCO2MeCO2MeCO2Et
Br
BINAP
969598989897
92
[(Ru(S-BINAP)X2] or [Ru(R,R-iPr-BPE)Br2]
10 atm H2, MeOH
BPE
---
99.3-
76
-
ee
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.
• Mixed Ru bisphosphine/diamine complexes afford much improved turnover numbers:
0.05% [Ru(R-xylBINAP)Cl2] + R-daipen
1 mol% KOtBu, 8 atm H2, iPrOHPhNMeAc
O
PhNMeAc
OH
87%. 97% ee
PAr2
Ar2P
Ru
Cl
Cl NH2
H2N
OMe
OMe
iPr
• Basic conditions allow dynamic kinetic resolution:
Noyori, J. Am. Chem. Soc. 2000, 122, 6510.
0.33% [Ru(R-xylBINAP)Cl2] + S-daipen
66 mol% KOH, 8 atm H2, iPrOH
98%, 82% ee
O
NHCO2tBu
OH
NHCO2tBu
(±)
Also for reduction of unfunctionalised ketones. Review: Noyori, Angew. Chem., Int. Ed., 2001, 40, 40.
Catalytic asymmetric hydrogenation of aminoketones
Asymmetric Transfer Hydrogenation of KetonesReduction with the aid of a hydrogen donor in the presence of a catalystReviews: Wills, Tetrahedron Asymmetry, 1999, 10, 2045; Noyori, Acc. Chem. Res. 1997, 30, 97.
MO
H
O
L L
R1
R2
Meerwein-Ponndorf-Verley type(main group or lanthanide metals)
(a) (b)
MH O
L LM
H O
L L
O
orM
H O
L L
R1R2
Metal hydride type:transition metals, iPrOH or formate as reductant
0.5% [RuCl2(hexamethylbenzene)2]
Ligand, iPrOH/KOH, 28CR
O
R
OH
X X
NHMe
OH
Ph
Ph
ligand=
XHOMeH
RMeMeEt
Yield947395
% ee927982
Aminoalcohols as ligands:
Arylalkylketones with electron rich aryl groups and benzocycloalkanones suffer from reversibility and give lower ee…but aminoalcohols are generally not compatible with the irreversible hydride donor formic acid
O
RS
NH2
N
Ph
PhRn
SO2Ar
RL
OH
RSRL
O O
MeO
O O
Ru
Cl
O OH
NH2
NH
Ph
Ph
O2S
HN
dend
J. Am. Chem. Soc., 1995, 117, 7562; J. Am. Chem. Soc., 1996, 118, 2521; Chem. Commun., 2001, 1488
iPrOH/KOH or HCO2H/Et3N
0.5%iPrOH/KOH
HCO2H/Et3N97% ee98% ee
72% ee97% ee
97% ee97% ee
91% ee99% ee
- supported and dendritic versions of the ligands have been prepared:
1 % [RuCl2(cymene)]2
1% ligand, HCO2H/Et3N
iPrOH/KOHHCO2H/Et3N
Run:
12345
% ee
96.596.796.796.495.0
conv.
9993868852
ligand:
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:
Ketone Reduction Catalyzed by Oxazaborolidines
N B
O
H PhPh
MeO
RS RS
OH
RL RL+ BH3.THF or catecholborane
(typically ca. 10% loading)
Review: Angew Chem. Int. Ed. 1998, 37, 1986
OH
X
X=HX=MeX=Cl
96.5% ee96.7% ee95.3% ee
tBu
OH
97.3% ee
OH
CO2Me
96.7% eePh
OH
Ph
97% ee
H17C6
OH
95% ee
OH
94% ee
Bu3Sn
TBSO
OH
O O
92% ee
Polymer-supported amino alcohol and in situ generation of borane
Angew. Chem. Int. Ed., 2001, 40,1109
O OH25% catalyst
NaBH4 / TMSCl
THF, reflux
HBr
MeONO2
% ee95.796.184.196.6
Yield98979799
R
R R
SO2
NOH
PhPh
Catalyst:
O
OLiAlH4 Al
H
ORLi+
OAl
O O LiH
R
O
R UnO
AlO O Li
H
R
O
Un R
R1 R2
O
R1 R2
OH
problems: stoichiometric, capricious to prepare, requires long reaction times at very low temperatures
i) (S)-BINOL
ii) ROH
(S)-BINAL-H
Un = aryl, heteroaryl, alkene, alkyne
enantioselectivity is largely electronic in origin:
_
electrostaticrepulsion
Asymmetric reduction of ketones: stoichiometric aluminium hydrides
Noyori, J. Am. Chem. Soc., 1984, 106, 6709, 6717
O
SGa
H
OR'
Li+
Un R
O
O
SGa
O
OR'
Li+ R
Un
H
Un R
OB
Ph
C-EtC
Me
Me
Me
_ _
catecholborane
Un R
Conditions:
2.5 mol% cat.,
-20oC, THF
2-furyl
PhCH=CH-
n-hexyl
Yield ee
95
76
70
60
91
81
75
63
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:
Ph CH3
O
Ph2PO
Ph2PO OBnO
O
O
Ph CH3
OH
N
N
O
N
O
R R
N
N
O
R
[(pigiphos)Rh(COD)]+ BF4-
87% ee
83% ee1:1:1 (R,R-pybox)/[Rh(COD)Cl]2/AgBF4
or 10:1:1 (S-pymox)/[Rh(COD)Cl]2/AgBF4
Ph2SiH2 or NpPhSiH2
then H3O+ work-up
65% ee
catalyst
(S-pymox)(S,S-pybox)pigiphos
Organometallics, 1991, 10, 560;Tetrahedron:Asymm., 1991, 2, 919
Hydrosilylation of imines/ketones: an alternative to hydrogenative reduction
O OH
NR
HNR
TiF F
TiH
2% cat, 97% ee, 84% yield
0.5% cat, 91% ee, 96% yield
pre-treated catalyst
5 eq. PMHS
THF, 15oC
slow addition of MeOH
5 eq. PMHS, THF, 60oC
slow addition of iBuNH2
pre-treated catalyst
precatalyst =
catalyst =
PhSiH3, piperidine,
MeOH
R = Bn
R = Ph 2% cat, 99% ee, 63% yield
Ph Ph
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)
Me3SiO Si OSiMe3
Me
H n
OEt
O
OEt
O
OEtOOEt
O
O
O
OMe
O
O
OMe
(S)-p-Tol-BINAP, CuCl
(S)-p-Tol-BINAP, CuCl
NaOtBu, PMHS, PhCH3
NaOtBu, PMHS, PhCH3
90%85% ee
93%80% ee
(S)-p-Tol-BINAP, CuCl
NaOtBu, PMHS, PhCH3
86%92% ee
Catalytic asymmetric hydrosilylation of enones/enoates
Buchwald, J. Am. Chem. Soc., 1999, 121, 9473; J. Am. Chem. Soc., 2000, 122, 6797