Transcript J. Am. Chem. Soc

Vy M. Dong , Jinquan Yu and their research work
Vy M. Dong
Professional Experience
University of Toronto:
Associate Professor, July 2010 to present.
Assistant Professor, July 2006 to June 2010.
National Institutes of Health Postdoctoral Fellow at the University of California at
Berkeley:
December 2003 to May 2006. Organometallic and supramolecular chemistry with Robert
Bergman and Kenneth Raymond
Graduate Student at UC Berkeley and the California Institute of Technology:
July 1998 to October 2003. Doctoral studies in organic synthesis with David MacMillan
Undergraduate Research Assistant at the University of California at Irvine:
June 1998. Undergraduate thesis on the tethered Biginelli condensation with Larry
Overman.
Education experience:
Harvard University - Cambridge, MA, USA
Jinquan Yu(余金权)
• Postdoctoral Fellow
Supervisor: E. J. Corey
February 2001 to May 2002
University of Cambridge - Cambridge, UK
• Junior Research Fellow (JRF) of St. John's College
October 1999 to October 2003
University of Cambridge - Cambridge, UK
• Ph.D. in Chemistry
Jonathan B. Spencer (1960-2008).
Supervisor: Jonathan B. Spencer (also Mattew Gaunt’s PhD Supervisor)
October 1994 to September 1999
Guangzhou Institute of Chemistry - Guangzhou, China
• M.Sc. in Chemistry
Supervisor: S.-D. Xiao（萧树德 ）
September 1988 to July 1990
Shanghai Institute of Organic Chemistry - Shanghai, China
• Coursework for M.Sc. degree
September 1987 to July 1988
East China Normal University - Shanghai, China
• B.Sc. in Chemistry
Top 5% on national examination for admission to SIOC
Supervisors: L.-X. Dai and B.-Q. Wu
September 1982 to July 1987
Positions:
The Scripps Research Institute - La Jolla, CA, USA
• Professor of Chemistry
August 2010 to Present
• Associate Professor, Department of Chemistry
July 2007 to August 2010
Brandeis University - Waltham, MA, USA
• Assistant Professor, Department of Chemistry
March 2004 to June 2007
University of Cambridge - Cambridge, UK
• Royal Society Research Fellow
October 2003 to February 2004
Guangzhou Institute of Chemistry - Guangzhou, China
• Teaching and Research Assistant in Organic Chemistry
October 1990 to September 1994
Dong’s research work
1.Rh(I) complexes to activate the C-H bond of aldehydes
History of Hydroacylation
Tetrahedron Lett. 1972,13,1287-1290
The reaction was discovered by Kiyoshi Sakai in 1972 as part in a synthetic route to
certain prostanoids(前列腺素 ).
The first catalytic application was reported by Roy G. Miller in 1976
J. Am. Chem. Soc., 1976,98,1281–1283
Hydroacylation as an asymmetric reaction was first demonstrated by James
and Young in 1983 (kinetic resolution) and by K. Sakai (Kyushu Univ.) (true
asymmetric synthesis) in 1989 J. Chem. Soc., Chem. Commun., 1983, 1215-1216
Tetrahedron Lett., 1989,30,6349-6352
Rh(I) planar square
Rh(III) octahedron
Zengming Shen and Vy M. Dong* J. Am. Chem. Soc., 2008, 130, 2916-2917
Ketone Hydroacylation
conventional strategies such as Corey-Nicolaou’s
PySSPy and Yamaguchi’s acid chloride
The coordinating ability of the
ether-oxygen can help suppress
decarbonylation and facilitate
hydroacylation.
Through the screening of various chiral
diphosphine ligands, they found that the
relation between phosphine basicity and
catalyst selectivity
Zengming Shen, Tom K.
Wooand* Vy M. Dong*
J. Am. Chem. Soc. 2009, 131,
1077
Mechanistic Insight
The turnover-limiting step:
insertion of the ketone C=O
bond to the rhodium hydride via
TS A
The ether oxygen is coordinated to Rh, and this coordination is critical for
promoting insertion over competitive decarbonylation.
But this protocol is limited in scope to ketoaldehydes bearing an ether
linkage!
J. Am. Chem. Soc. 2009, 131, 15608–15609
Counterion effects on reactivity: catalysts with more
strongly coordinating counterions gave better selectivity for
hydroacylation over decarbonylation
Counterions’ coordinating strengths:
SbF6- < BF4- < -OTf <-OMs<NO3- < ClThe reason of choosing AgNO3 as the optimal
additive is that nitrate is less strongly
coordinating than Cl (giving shorter reaction
times) but coordinating enough to suppress
decarbonylation and assist in enantioinduction
The appropriate choice of counterion was crucial in
suppressing decarbonylation and controlling enantioselectivity
The presence of a nitrogen atom not
only promotes faster reactivity but
also suppresses decarbonylation
completely.
Chem. Sci. 2011, 2,407-410
Rh-Catalyzed Intramolecular/ Intermolecular Olefin Hydroacylation
Formation of medium-sized ring heterocyclic ketone J. Am. Chem. Soc. 2009, 131, 6932.
Challenge: regio-selectivity
Coordination of X to Rh helps promoting olefin
hydroacylation over olefin isomerization, aldehyde
decarbonylation, and catalyst decomposition
Regioselectivity would depend on the catalyst choice and
substrate structure (i.e. X, tether length, and olefin substitution)
If reductive elimination were turnover-limiting in our case, D would be scrambled into the αposition of 11-D. However, we observed that products 10-D and 11-D had D at only the βposition. This lack of D scrambling suggests that reductive elimination is not the turnoverlimiting step in our catalytic system.
J. Am. Chem. Soc. 2010, 132, 16330–16333
Challenge was still in regiocontrol
While reactive in Rh-catalyzed intermolecular hydroacylation,terminal olefins
tend to give achiral, linear products or mixtures of regioisomers
Bolm, C. Adv. Synth. Catal. 2007, 349, 1185.
H. Suemune（Kyushu Univ）,
J. Org. Chem. 2004, 69, 11441150
1a:salicylaldehyde
J. Am. Chem. Soc. 2010, 132, 16354–16355
Challenge: In general, intermolecular hydroacylation is difficult to achieve due to
competing pathways such as decarbonylation and catalyst decomposition
2.Palladium-Catalyzed C–H Bond Functionalization
first intermolecular palladium-catalyzed transformations of sp2C-H bonds to C-S
J. Am. Chem. Soc. 2009, 131, 3466–3467
Chelation-assisted strategy
Pervious work: sp2 C-H bonds to C-O, C-X, C-C, and C-N (Yu, Sanford
and Ellman’s work)
Angew. Chem. Int. Ed. 2011, 50, 932 –934
The first direct observation of C-S bond-forming reductive elimination from
Pd (IV) complexes; the first Pd (IV) complexes containing a Pd-SO2R bond
These results support the feasibility of
palladium-catalyzed sulfonylation and
desulfitative C-C cross-coupling
reactions through a Pd (II)- Pd (IV)
catalytic cycle
Chem. Sci., 2010, 1, 331–336
Using sodium persulfate, a nontoxic,
environmentally benign, and easy-tohandle oxidant
Synlett. 2011, in press
Invited contribution in honor of Xiyan
Lu and Li-Xin Dai
Tetrahedron, 2009, 65, 3062–3068
Nitrosoalkene and vinylnitrene represent two important intermediates that
have been relatively elusive and underutilized for C–N bond formation
3.Others
Chem. Sci. 2011, 2,544
a. Ru-catalyzed activation of sp3 C–O bonds
Direct insertion into electron-rich bonds such as typically insert ethereal C–O bonds
A selective intramolecular alkyl transfer
process.
This observation suggests that reversible sp3
C–H bond activation is taking place
b. Negishi cross-coupling between organozinc reagents and CO2
J. Am. Chem. Soc. 2008, 130, 7826–7827
J. Am. Chem. Soc. 2008, 130, 6058–6059
J. Am. Chem. Soc. 2006, 128, 8706
Work of Iwasawa (Tokyo Institute of
Technology)
基本原理：
C-H键直接与Pd发生氧化加成
(top) electrophilic metalation of the aromatic C–H bond pathway（SArE）
(bottom) Concerted proton transfer metallation pathway
K. Fagnou,Science，2007,316,1172
Fujiwara-type reaction
1.杂原子的配位定位作用，同
时使C-H键更易活化
2.Various E+
早期研究: 始于C(sp2)-H键的烯化
I Moritani; Y Fujiwara. Tetrahedron Lett. 1967, 8, 1119.
Y. Fujiwara, I. Moritani, J. Am. Chem. Soc. 1969,91,7166
Drawback:
1使用大大过量的芳烃（一部分作为溶剂）
2缺少区域选择性控制
Y Fujiwara ,Science, 2000, 287, 1992
highly electrophilic cationic species:
Pd(O2CCF3)+
One vinyl H or D in all adducts was mainly
from the solvent acid, which presumably
results from the protonation of vinyl-Pd
complex IMc by TFA-d1 or TFA
The involvement of s-aryl-Pd complexes IMa has been confirmed by the 1H
NMR spectrum from the disappearance of the aryl H of 1 in the reaction with l eq
of Pd(OAc)2 in TFA in a few minutes at room temperature.
The fact that the hydroarylation reaction failed in other solvents such as
acetic acid indicates the necessity of TFA for the formation of cationic
Pd(II) species and for the protonation of a vinyl-Pd intermediate IMc to
complete the catalytic cycle.
X. Lu, G. Zhu, S. Ma, Tetrahedron Lett. 33, 7205 (1992).
A possible mechanism would be the electrophilic attack of the aromatic C–H
bond by cationic Pd(II) species to form IMa followed by coordination of
alkyne to give IMb. A trans insertion of C–C triple bonds to the s-arylPd bond (23–25) results in IMc, and 1/1 arene/alkyne adduct would be
released from Pd(II) (24) upon protonation of IMc
后来通过引入导向基团，提高区域选择性
Masahiro Miura ,J. Org. Chem.,1998,63,5211–5215
J. Am. Chem. Soc., 2002, 124, 1586-1587
C(sp2)-H键和C(sp3)-H键的芳基化和烷基化
K. Fagnou, Science, 2007,316,1172
Ar-H+Ar’-H→Ar’-Ar 比较困难
Ar-H 和 Ar’-H很容易发生自身偶联，减
少交叉偶联产物
homo-coupling VS cross-coupling
3 eq. Cu(OAc)2 and arene (~30 eq)
palladium(II) complexes can react via SArE
with good selectivity for electron-rich
arenes
Organometallics, 2006, 25 ,5973-5975
J. Am. Chem. Soc.,2006,128,1066–1067
Yu’s research work
Metal-catalyzed carbon-carbon and carbon-heteroatom bond forming reactions
based on C-H activation
Pd(II)/Pd(IV), Pd(II)/Pd(0) and Cu(II)/Cu(0) redox systems
1.Activation of sp2 C-H bond
2.Activation of sp3 C-H Bonds
1.Activation of sp2 C-H bond
Yuzo Fujiwara, Science 2000,287, 1992
Science, 2009, 323, 1593
2.Activation of sp3 C-H Bonds
Pd(II)-Catalyzed Carboxylation of Aryl and Vinyl C-H Bond
J. Am. Chem. Soc. 2008, 130, 14082–14083
X-ray crystallography of the first C-H insertion intermediate isolated
from the cyclometalation of carboxylic acids.
Angew. Chem. Int. Ed. 2009, 48, 6097 –6100
Challenge: Pd(II)-catalyzed intermolecular alkylation of C-H bonds
with alkyl halides
目前C-H活化多为形成C(sp2)C(sp2)的反应，烷基化反应相
对较少
not a Friedel–Crafts-type
reaction
Although the oxidation of the arylpalladium(II) intermediate by MeI to Pd(IV) was previously
proposed (intermediate 8), in light of previous discoveries that arylpalladium species react
with electrophiles such as aldehydes and ketones,direct s-bond metathesis between the aryl–
Pd bond and the alkyl halide cannot be ruled out (intermediate 9)
Pd-catalyzed arene C–H olefination
Science,2010,327,315-319
Angew. Chem. Int. Ed. 2010, 49, 6169–6173
Challenge:
1. the substrates that are typically effective in palladium-catalyzed C–H activation
are synthetically restrictive, either because they are limited to electron-rich arenes
or heterocycles, or because they possess impractical chelating functional groups to
promote metalation. These directing groups include those thatare irremovable and
recalcitrant to undergo further synthetic elaboration, such as Py, and those that are
removable but require several steps for installation and detachment, such as
oxazoline.
2. methods for effecting position-selective C–H activation on multiply substituted
arenes , particularly via ligand control, remain underdeveloped
No traditional Mizoroki-Heck reaction product
Meta-olefination of highly electron-deficient arene
J. Am. Chem. Soc. 2009, 131, 5072–5074
Fujiwara-type reactions using electrondeficient arenes using electrondeficient
arenes under various reported conditions have two problems：
1.electron-deficient arenes were unreactive due to their poor coordination with
Pd(OAc)2
2.reoxidation of Pd(0) by O2 was not possible in the absence of electron-rich arenes,
external ligands, or co-oxidants
Py: the most efficient ligands to promote the reoxidation of Pd(0) by
oxygen
Yu hypothesized that, in these
systems,displacement of the pyridyl
ligand by the electron-deficient arene
substrate is energetically disfavored
due to the strength of the Pd-N bond.
Even upon prior loss of acetate and
formation of the corresponding
Py2Pd(OAc)+, the resulting complex
remained insufficiently
electrophilic for C-H activation to take
place
increase in steric bulk at the 2 and 6
positions of the pyridine ring to weak PdN bond strength
the bond length of Pd-N is 0.05 Å longer than that of (Pyridine)2Pd(OAc)2
Py2Pd(OAc)2 complexes are highly stable under the same conditions
Science, 2009, 323, 1593
This paper was featured in:
Perspectives in Science: Copper Puts Arenes in a Hard Position
RSC Chemistry World: Copper catalysts give meta aromatics
Research Highlights in Nature Chemistry: Electrophilic arylation: Substitution
success
Chemical and Engineering News: Dodging The Substitution Laws
Science News: Helping Molecules Reach Meta
Angewandte Chemie: Meta-Selective Transition-Metal Catalyzed Arene C-H Bond
Functionalization
This paper was voted as one of the top 12 papers of 2009 by Chemical and
Engineering News Chemical Year in Review 2009
How to access the isomer that is not anticipated by
these rules?
Solutions to this problem often require numerous FG additions or
manipulations in order to tailor the directing electronic properties of the
precursor to furnish the desired product
吲哚能发生亲电取代反应，多取代于3号位
Sanford, J. Am. Chem. Soc. 128, 4972
J. Am. Chem. Soc. 130, 8172
Although we cannot be certain of the precise mechanism of the reaction at
this stage, a possible rationalization could involve the highly electrophilic
Cu(III)-aryl species activating the aromatic ring sufficiently to permit an
anti–oxy-cupration of the carbonyl group of an acetamide across the
2,3 positions on the arene ring
We cannot rule out coordination of the Cu(III) species
at the ortho position, followed by a migration to the
meta site and arylation. However, we do not see any
sign of ortho-arylation that may be expected through
this pathway
Yuzo Fujiwara (Kyushu University)
Masahiro Miura (Osaka Univ.)
Melanie Sanford (UMichigan)
Christina White (UIUC)
Matthew Gaunt (Cambridge)
Keith Fagnou(U Ottwa)
Passed away in Nov. 2009