Transcript Catalytic, Enantioselective Nucleophilic Addition to N

Trost’s Palladium Catalysed Asymmetric
Allylic Alkylation
(Pd-AAA)
Literature Meeting
Charette’s group
Miguel St-Onge
October 9th, 2007
1
Presentation
1. Trost and Palladium
2. p-allyl complexes
i.
ii.
iii.
iv.
3.
4.
5.
6.
7.
8.
9.
Stereochemistry of oxidative addition and nucleophilic attack
Counter anion effects
Syn vs anti complexes
Nucleophilic approach on allyl terminus
Ligands and cartoon model
Classes of enantiodiscrimination processes
Types of nucleophiles and their application to total synthesis
Exceptions to the model
AAA with other metals
Total synthesis of Tipranavir
Conclusion
2
Pr. Barry M. Trost
 Born in 1941 in Philadelphia
 Received B.A. From University of Pennsylvania (1962)
 Received Ph.D. at MIT under H.O. House’s supervision (1965)
 Professor of chemistry at University of Wisconsin (1969)
Vilas research professor of chemistry (1982)
 Professor of chemistry at Standford University (1987)
Takami professor of humanities and sciences (1990)
 803 publications (2006)
 38 honors and awards
 14 Patents
Barry Trost web page at www.stanford.edu/group/bmtrost
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Palladium
•Discovered in 1803 by William Hyde Wollaston
•Isolated from (NH4)2PtCl6
•Name comes from Greek goddess of wisdom, Pallas or Palladion
•Atomic number 46
•[Kr] 4d10
•Pd0 = 18e square planar complexes
•Pd(II) = 14e square planar complexes
2+
Ph3P
Ph3P
Pd
PPh3
PPh3
Cl
NCMe
Pd
NCMe
Cl
4
p-Allyl Palladium Complex and C-C Bond Formation
Trost, B. M.*; Weber, L. J.Am.Chem.Soc. 1975, 97, 1611-1612.
5
Trost’s Study
Trost, B.M; Weber, L. J. Am. Chem. Soc. 1975, 97, 1611-1612
6
Study conclusion
Conclusions:
-Stereospecificity of allylic alkylation has potentially important consequences in the
application of the method for the creation of stereochemistry in acyclic and
macrocyclic systems.
- Alkylation occurs on the face of the p-allyl unit opposite to that of the palladium and
use of soft nucleophiles are required for successful alkylation
7
Stereochemistry of Oxidative Addition
Hayashi, T.*; Hagihara, T.; Konishi, M.; Kumada, M. J. Am. Chem. Soc. 1983, 105, 7768-7770.
8
Stoichiometric vs Catalytic
Conclusions:
- Oxidative addition of palladium proceed with inversion of configuration and addition
on p-allyl palladium proceed also with inversion of configuration.
- Net retention of configuration also occurs in enantiomeric catalytic system
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Catalytic Cycle
10
Counter Anion Effects
Amatore, C.; Jutand, A.; M’Barki, M. A.; Meyer, G.; Mottier, L. Eur. J. Inorg. Chem. 2001, 873.
Cantat, T.; Génin, É.; Giroud, C.; Meyer, G.; Jutand, A.* J. Org. Chem. 2003, 687, 365-376.
11
Syn Complex vs Anti Complex (p-s-p equilibration)
Trost, B.M.; Machacek, M.R.; Aponik, A. Acc. Chem. Res. 2006, 39, 747-760.
12
Nucleophile Approach
Pd
R
H
R
H
H
Nu
Exo approach
Pd
R
H
R
H
H
Nu
endo approach
• Nucleophile addition is considered as a SN2-like displacement
• Attack must be anti to the Pd leaving group (180o)
• High impact for ligand working model analysis
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Allyl Terminus
Less substituted terminus
More substituted terminus
Small and s-donating ligands
Bulky ligands
Metal at higher oxidation state
Good p-acid ligands
Pd coordination with more electron poor olefins
Trost, B.M.; Machacek, M.R.; Aponik, A. Acc. Chem. Res. 2006, 39, 747-760.
Redesign Catalytic Cycle
Ph
Nu
L
Ph
or
Pd
L
Ph
Nu
X
Decomplexation
Complexation
L
L
L
Pd
Ph
L
L
Pd
X
Nu
Nu
L
Nu
Pd
L
X
Ph
Oxidative addition
(ionization)
Nucleophilic addition
Ph
L Pd L
Cl
L
Ph
Ph
or
Pd
Ph
L Pd L
Cl
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Successful Ligands
Pfaltz
Togni, Spindler
Evans
CN
P(Cy)2
N
R
PPh2
FeCp
H
N
Ph2 P
R
S
i-Pr
t-Bu
R= CO 2Me, CH 2 OSiMe2 t-Bu,
CMe 2OH
Faller
O
Morimoto
S
PPh 2
PPh 2
N
Ph
SPh N
Ph
Tognie, A.; Breutel., C.; Schnyder, A.; Spindler, F.; Landert, H.; Tijani, A J. Am. Chem. Soc. 1994, 116, 4062-4066.
Pfaltz, A Acc. Chem. Res. 1993, 26, 339-345.
Evans, D.A.; Campos, K.R.; Tedros, J.S.; Michael, F.E.; Gagné, M.R. J. Am. Chem. Soc. 2000, 122, 7905-7920.
Faller, J.W.; Wilt, J.C. Organometallics, 2005, 24, 5076-5083.
Morimoto, T.; Tachibana, K.; Achiwa, K. Synlett, 1997, 783-785.
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Trost’s Classic Ligands
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Cartoon Model
Trost, B.M.; Toste, F.D. J. Am. Chem. Soc., 1999, 121, 4545-4554.
Lloyd-Jones G.C. Et. Al. Pure Appl. Chem., 2004, 76, 589-601.
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Classes of Enantiodiscriminating Processes
•
•
•
Ionization of the leaving group
Class A- Desymmetrization of meso
diester
Class B- Desymmetrization of prochiral
leaving group on the same carbon
Class C- Unsymmetrical p-allyl Pd
complexes (achiral)
•
•
Addition of the nucleophile
Class D- Meso-like p-allyl Pd complex
Class E- Unsymmetrical p-allyl Pd
complexes (chiral)
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Class A- Desymmetrization of meso Diester
Trost, B.M.; Dudash, J., Jr.; Dirat, O. Chem-Eur. J. 2002, I81, 259-268.
Trost, B.M.; Patterson, D.E., J. Org. Chem., 1998, 63, 1339-1341.
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Class B- Desymetrisation of Prochiral Leaving Group on the Same Carbon
Trost, B.M.; Lee, C.B. J. Am. Chem. Soc. 1998, 120, 6818-6819.
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Class B- Desymmetrization of Prochiral Leaving Group on the Same Carbon
Trost, B.M.; Lee, C.B. J. Am. Chem. Soc. 1998, 120, 6818-6819.
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Class C- Unsymmetrical p-Allyl Pd Complexes (Achiral)
Trost, B.M.; Machacek, M.R. Angew. Chem., Int. Ed. 2002, 41, 4693-4697.
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Class C- Unsymmetrical p-Allyl Pd Complexes (Achiral)
Trost, B.M.; Machacek, M.R. Angew. Chem., Int. Ed. 2002, 41, 4693-4697.
24
Class D- Meso-like p-Allyl Pd Complex
Trost, B.M.; Dudash, J., Jr.; Hembre, E.J. Chem.-Eur. J. 2001, 16, 1619-1629.
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Class D- Meso-like p-Allyl Pd Complex
Trost, B.M.; Dudash, J., Jr.; Hembre, E.J. Chem.-Eur. J. 2001, 16, 1619-1629.
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Class E- Unsymmetrical p-Allyl Pd Complexes (Chiral Acyclic Substrate)
Trost, B.M.; Bunt, R.C.; Lemoine, R.C.; Calkins, T.L. J. Am. Chem. Soc. 2000, 122, 5968-5976.
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Class E- Unsymmetrical p-Allyl Pd Complexes (Chiral Cyclic Substrate)
Trost, B.M.; Toste, F.D. J. Am. Chem. Soc. 2003, 125, 3090-3100.
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Lactone Isomerization
Trost, B.M.; Toste, F.D. J. Am. Chem. Soc. 2003, 125, 3090-3100.
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Chirality at the Nucleophile
Trost, B.M.; Radinov, R.; Grenzer, H.M. J. Am. Chem. Soc. 1997, 119, 7879-7880.
Trost, B.M.; Schroeder, G.M.; Kristensen, J Angew. Chem., Int. Ed. 2002, 41, 3492-3495.
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Carbon Nucleophiles in Total Synthesis
Malonate type:
Chapsal, B.D.; Ojima, I. Org. Lett., 2006, 8, 1395-1398.
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Carbon Nucleophiles in Total Synthesis
Sulfone Type:
Nitro type:
Trost, B. M.; Chupak, L. S.; Lubbers J. Am. Chem. Soc. 1998, 120, 1732-1740.
Trost, B. M.; Surivet, J.-P. Angew. Chem., Int. Ed. 2000, 39, 3122-3124.
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Oxygen Nucleophiles in Total Synthesis
Primary alcohols:
Carboxylates:
Trost, B. M.; Weiping, T.; Schulte, J. L. Org. Lett. 2000, 2, 4013-4015.
Trost, B. M.; Kondo, Y. Tet. Let. 1991, 32, 1613.
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Oxygen Nucleophiles in Total Synthesis
Phenols
Trost, B. M.; Toste, F. D. J. Am. Chem. Soc. 1998, 120, 9074-9075.
Trost, B. M., Tang, W. J. Am. Chem. Soc., 2002, 124, 14542-14543.
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Nitrogen Nucleophiles
Amines
• Mono versus bisalkylation of primary amines
• Regioselectivity on Pd p-allyl system
• Speed of nucleophile versus p-s-p equilibration
Trost, B. M.; Krische, M. J.; Radinov, R.; Zanoni, G. J. Am. Chem. Soc. 1996, 118, 6297-6298.
You, S. L.; Zhu, X. Z.; Luo, Y. M.; Hou, X. L.; Dai, L. X. J. Am. Chem. Soc. 2001, 123, 7471-7472.
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Nitrogen Nucleophiles in Total Synthesis
Azides
Trost, B. M.; Pulley, S.R. J. Am. Chem. Soc 1995, 117, 10143-10144.
Trost, B. M.; Cook, G. R. Tet. Lett., 1996, 37, 7485-7488.
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Nitrogen Nucleophiles in Total Synthesis
Sulfonamide
Trost, B. M.,; Oslob, J. D.; J. Am. Chem. Soc. 1999, 121, 3057-3064.
Mori, M.; Nakanishi, M.; Kajishima, D.; Sato, Y. Org. Lett. 2001, 3, 1913-1916.
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Nitrogen Nucleophiles in Total Synthesis
Imides
Trost, B. M.,; Patterson, D. E.; Chem. Eur. J. 1999, 5, 3279
Buschmann, N.; Rueckert, A.; Blechert, S. J. Org. Chem. 2002, 67, 4325-4329.
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Nitrogen Nucleophiles in Total Synthesis
Trost, B. M.; Shi, Z. J. Am. Chem. Soc. 1996, 118, 3037-3038.
Trost, B. M.; Madsen, R.; Guile, S. D.; Tet. Lett., 1997, 38, 1707-1710.
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Sulfur Nucleophiles Pd -AAA
Trost, B. M.; Organ, M. G.; O’Doherty, G. A. J. Am. Chem. Soc. 1995, 117, 9662-9670.
Trost, B. M.; Crawley, M. L.; Lee, C. B. J. Am. Chem. Soc. 2000, 122,6120-6121.
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Exceptions
Trost, B. M.; Toste, D. F. J. Am. Chem. Soc. 2000, 122, 11262-11263.
Trost, B.M.; Machacek, M.R.; Aponick, A. Acc. Chem. Res. 2006, 39, 747-760.
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Exceptions
Trost, B.M.; Machacek, M.R.; Aponick, A. Acc. Chem. Rev. 2006, 39, 747-760.
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Exceptions
Trost, B.M.; Gunzner, J.L.; Dirat, O.; Rhee, Y. H. J. Am. Chem. Soc. 2002, 124, 10396-10415.
43
AAA with Other Metals: Tungsten
Lloyd-Jones, G.C.; Pfaltz, A. Angew.Chem., Int. Ed., 1995, 34, 462.
Co, T.T.; Paek, S.W.; Shim, S.C.; Cho, C.S.; Kim, T.-J.; Choi, D.W.; Kang, S.O.; Jeong, J.H Organometallics, 2002, 22, 1475-1482.
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AAA with Other Metals: Iridium
Ph
Ph
N
Cl
O
P
Ir
O
Ohmura, T.; Hartwig J.F. J. Am. Chem. Soc. 2002, 124, 15164-15165.
Kiener, C.A.; Shu, C.; Incarvito, C.; Hatrwig, J.F. J. Am. Chem. Soc. 2003, 125, 14272-14273.
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Novel Iridium Utilisation
•
Preparation of -Substituted Allylboronates by Chemoselective IridiumCatalyzed Asymmetric Allylic Alkylation of 1-Propenylboronates
- Peng, F.; Hall*, D. G. Tet. Lett. 2007, 18, 3305-3309
•
Salt-Free Iridium-Catalyzed Asymmetric Allylic Aminations with N,NDiacylamines and ortho-Nosylamide as Ammonia Equivalents
- Weihofen, R.; Tverskoy, O.; Helmchen, G.; Angew. Chem., Int. Ed. 2006, 33, 5546-5549
•
Very Efficient Phosphoramidite Ligand for Asymmetric Iridium-Catalyzed
Allylic Alkylation
- Alexakis*, A.; Polet, D.; Org. Lett. 2004, 20, 3529-3532
•
Regio- and Enantioselective Iridium-Catalyzed Allylic Alkylation with In Situ
Activated P,C-Chelate Complexes
- Lipowsky, G.; Miller, N.; Helmchen, G. Angew. Chem., Int. Ed. 2004, 43, 4595 –4597
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AAA with Other Metals: Molybdenum
Trost, B.M.; Dogra, K. J. Am. Chem. Soc. 2002, 124, 7256-7257.
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Molybdenum AAA Transition State
Krska, S. W.; Hughes, D. L.; Reamer, R. A.; Mathre, D. J.; Sun, Y.; Trost, B. M. J. Am. Chem. Soc. 2002, 124 (43), 12656-12657.
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Synthesis of Tipranavir (Aptivus)
*
O
Cl
1) EtMgBr, THF, 0oC
2) NaOH 1M, Et2O, r.t.
86% over 2 steps
O
OH
5 mol% Pd/C
H2 1 atm
MeOH, pyr.
r.t., 99%
OPMB
Pd
(S,S)-Standard (3 mol%)
Pd2dba3CHCl3 (1 mol%)
1 mol% Et3B, PMBOH (1 eq.).
O
B
OPMB
OH
PHI, 10mol% Pd(OAc)2,
40 mol% P(o-Tol)3
Tol., Et3N, reflux, 92%
OPMB
69%, 98% ee
Ph
OH
OPMB
Ph
1) DMP, CH2Cl2, r.t.
2) Ph3P=CH2, THF, reflux,
94% (two steps)
OPMB
Ph
Trost, B.M.; Andersen, N.G. J. Am. Chem. Soc. 2002, 124, 14320-14321.
CHO
1) Cathecolborane
(Ph3P)3RhCl, THF, 25oC
NaOH (3N), H2O2 (30%)
2) DMP, CH2Cl2, r.t.
88% (two steps
OPMB
Ph
49
Synthesis of Tipranavir (Aptivus)
15 steps,
25%yield
Trost, B.M.; Andersen, N.G. J. Am. Chem. Soc. 2002, 124, 14320-14321.
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Conclusion
•
•
•
•
•
•
•
•
•
•
High yields and enantioselectivities are obtain
5 mechanisms for enantiodiscrimination
Diversity of bond type (C-C, C-O, C-N, C-S)
Chirality can be set at substrates, nucleophiles or both
AAA react with sp3 instead of sp2 centers
Transforms achiral, prochiral and more importantly chiral racemic substrates
into enantiopure compounds (through DYKAT)
Cartoon model developped to predict final stereochemistry (almost no
exceptions)
Versatile method using mild conditions
Usefull central strategy for total synthesis
Scope have been expanded to other metals
51