Rapid two-step synthesis of drug-like polycyclic substances by sequential multi-catalysis cascade reactions

Article abstract of DOI:10.1039/b920152a

An efficient amino acid-/self-/base-/ruthenium-/thermal-catalyzed two-step process for the synthesis of functionalized drug-like carbocycles was achieved through combinations of cascade TCRA/C-allylation/enyne-RCM/Diels-Alder reactions as key steps starting from simple acyclic substrates. In this communication, we report the two-step synthesis of drug-like carbocycles through a combination of organocatalysis with ruthenium-catalysis.

Full text of DOI:10.1039/b920152a

View Article Online / Journal Homepage / Table of Contents for this issue
COMMUNICATION
www.rsc.org/obc | Organic & Biomolecular Chemistry
Rapid two-step synthesis of drug-like polycyclic substances by sequential
multi-catalysis cascade reactions†
Dhevalapally B. Ramachary,* Rumpa Mondal and Chintalapudi Venkaiah
Received 28th September 2009, Accepted 19th October 2009
First published as an Advance Article on the web 28th October 2009
DOI: 10.1039/b920152a
An efficient amino acid-/self-/base-/ruthenium-/thermal-
catalyzed two-step process for the synthesis of functionalized
drug-like carbocycles was achieved through combinations
of cascade TCRA/C-allylation/enyne-RCM/Diels–Alder re-
actions as key steps starting from simple acyclic substrates. In
this communication, we report the two-step synthesis of drug-
like carbocycles through a combination of organocatalysis
with ruthenium-catalysis.
generation of drug-like carbocycles 11 and 12 via combination
of TCRA, C-allylation (C-A), enyne-ring closing metathesis
(enyne-RCM) and Diels–Alder (DA) reactions as key processes
(Scheme 1).
Herein, we discovered a novel and green technology for the
two-step synthesis of highly substituted drug-like carbocycles 11
and 12 using proline-/self-/potassium carbonate-/ruthenium-/
thermal-catalysis through cascade TCRA, C-A, enyne-RCM and
DA reactions as key steps starting from commercially available
2-ethynyl-benzaldehydes 1, CH-acids 2, organic-hydrides 3, allyl
bromide, diazomethane, reactive dienophiles 10, L-proline 4,
K2CO3 and Grubbs’ 1st or 2nd generated ruthenium catalysts,
an approach we call the “multi-catalysis cascade (MCC) approach
to carbocycles” (Scheme 1).4a–o In this communication, we report
a new synthetic strategy by the combination of organocatal-
ysis with enyne-RCM/DA reactions to deliver complex
carbocycles.
Highly functionalized drug-like carbocycles are of considerable
importance in the pharmaceutical industry.1 As such, the devel-
opment of new and more general green one-pot cascade methods
for their preparation is of significant interest for the development
of new drugs.2a–i Especially, functionalized polycyclic carbocycles
have attracted considerable attention as a result of their structural
complexity, biological activity and their presence in a variety of
natural and unnatural products.2j–l Thus, the diversity-oriented
synthesis of polycyclic carbocycles represents an important task
because of the synthetic challenge, and also widespread occurrence
of such structural motifs and their use as building blocks. Herein,
we report the multi-catalytic cascade approach to the high-yielding
synthesis of functionalized drug-like carbocycles from a two-
step sequence via a “combination of amino acid-/self-/base-/
ruthenium-/thermal-catalysis”.
Recently olefin metathesis of dienes and enynes catalyzed
by Grubbs’ catalysts provided a general platform to a variety
of carbocycles with good yields.3 The manifestation of olefin
metathesis technology triggered a burst of activity in the synthesis
of a huge variety of differently substituted carbocycles. Reactions
performed in a sequential cascade approach can generate the
desired targets efficiently in a single reaction vessel without the
need to purify at each step. A particularly attractive green cascade
process occurs when two or more sequential cascade reactions are
triggered by more than two catalysts in one-pot. The catalytic
ability and orthogonal catalysis of L-proline to function as a
soft catalyst for the cascade three-component reductive alkylation
(TCRA) reactions has led to several examples, where combination
of this TCRA with other transformations in one-pot provided
efficient new entries into useful drug intermediates.4a–i
We found that the amino acid L-proline 4 readily catalyzes the
olefination of 1a with ethyl cyanoacetate 2a to furnish the active
olefin, which on in situ treatment with Hantzsch ester 3a produced
the TCRA product 5aa with very good conversion in EtOH or
◦
DMSO at 25 C for 1 h, which on treatment with allyl bromide
and K2CO3 at 25 ◦C for 11 h furnished the ene-yne product
6aa with 95% yield (result not shown in Table 1). The same
sequential cascade TCRA/C-A reaction with in situ generated
hydride source, 2-phenyl-2,3-dihydro-1H-benzoimidazole 3b also
furnished the product 6aa with 93% yield (Table 1, entry 1). The
optimum conditions involved the use of 20 mol% catalyst 4 and 8
equiv. of K2CO3 in cascade TCRA/C-A reaction of 1a, 2a, 3a/3b
◦
and allyl bromide in EtOH or DMSO at 25 C to furnish 6aa in
very good yield.
With the optimized reaction conditions in hand, the scope
of the sequential one-pot cascade TCRA/C-A reactions was
investigated. A variety of CH-acids 2a–l were reacted with
1 equiv. of 2-ethynyl-benzaldehyde 1a, 1 equiv. of organic hydride
3a/3b and 5 equiv. of allyl bromide under the sequential catalysis
by 20 mol% of L-proline-/self and K2CO3 in DMSO at 25 ◦C
for 0.75 to 24 h (Table 1). Acyclic and cyclic CH-acids 2a–l
generated the expected ene-yne products 6 with excellent yields
(Table 1). Reaction of (1R,2S,5R)-cyano-acetic acid 2-isopropyl-
5-methyl-cyclohexyl ester 2f with 1a, 3b and allyl bromide under
L-proline-/self-/K2CO3-catalysis furnished the product (-)-6af,
but unfortunately we observed only 1 : 1 dr (Table 1, entry 6).
Reaction of Meldrum’s acid 2h with 1a, 3a and allyl bromide under
L-proline-/self-/K2CO3-catalysis furnished the product 6ah in
76% yield (Table 1, entry 8). In a similar manner, ene-yne
compound 6ai was furnished as the major product with 60% yield
(Table 1, entry 12). Interestingly, reaction of cyclic CH-acids 2j–l
During our studies on amino acid-/self-catalyzed cascade
TCRA reactions,4a–i we noted that functionalized 2-ethynyl-
benzaldehydes 1 can serve as suitable starting materials for the
School of Chemistry, University of Hyderabad, Hyderabad-500 046, India.
E-mail: ramsc@uohyd.ernet.in; Fax: +91-40-23012460
† Electronic supplementary information (ESI) available: Experimental
procedures and analytical data (1H NMR, 13C NMR and HRMS) for
all new compounds. See DOI: 10.1039/b920152a
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 321–325 | 321
©

View Article Online
Scheme 1 Synthesis of drug-like carbocycles via a two-step sequence.
with 1a, 3a and allyl bromide under L-proline-/self-/K2CO3-
catalysis furnished the ene-yne compounds 6aj–al as major
products in 50-65% yields with accompanying by TCRA/
O-A by-products 13aj–al in 25-50% yields as shown in Table 1,
entries 13-15. This may be due to the highly acidic nature of
cyclic CH-acids 2j–l compared to acyclic CH-acids 2a–g in the
compounds 5aj–al. By-products 13aj–al can be converted into
required ene-yne compounds 6aj–al by thermal-catalysis through
Claisen rearrangement and by-product 13al was transformed into
ene-yne 6al in 75% yield after heating at 120 ◦C for 23 h in toluene
(eq S1, see Supporting Information†). Structure of products
6aa–al was confirmed by NMR and mass analysis.
For the synthesis of ene-ynes 7aha–ahc containing mal-
onates, we utilized the in situ generation and esterfication
of methoxycarbonylketenes with alcohols via the sequential
MCC one-pot TCRA-/alkylation-/ketenization-/esterification
(TCRA/A/K/E) followed by C-allylation (C-A) reactions of
2-ethynyl-benzaldehyde 1a, Meldrum’s acid 2h, Hantzsch ester
3a, diazomethane, alcohols a–c and allyl bromide via iminium-/
self-/self-/self-/self-/base-catalysis in one-pot.4i Interestingly,
L-proline-/self-catalyzed cascade TCRA reaction of Meldrum’s
acid 2h and 2-ethynyl-benzaldehyde 1a with organic-hydride 3a
in MeOH a at 25 ◦C for 1 h furnished the expected TCRA
product 5ah in >99% conversion, which on in situ treatment
with ethereal diazomethane at 0 ◦C → 25 ◦C for 2 h furnished
the expected dimethyl-2-(2-ethynyl-benzyl)-malonate 5¢aha with
99% conversion, which on in situ treatment with allyl bromide
and K2CO3 furnished the expected ene-yne compound 7aha in
65% yield (Table 1, entry 9). In a similar manner, we synthesized
two more ene-ynes 7ahb–ahc with good yields by performing the
sequential MCC reactions of TCRA/A/K/E/C-A reactions in
ethanol b and t-butanol c solvents respectively as shown in Table 1,
entries 10 and 11.
With the ene-yne library in hand, first we focused on the
optimization of enyne-RCM reaction on 6aa by changing reactions
conditions as shown in Table 2. Interestingly, enyne-RCM reaction
of 6aa using Grubbs’ 1st generation catalyst in CH2Cl2 at 25 ◦C for
14 h furnished the highly functionalized benzocycloheptene 8aa
in 55% yield; but the same reaction with Grubbs’ 2nd generation
catalyst also furnished the 8aa in 55% yield (Table 2, entries 1
and 2). Enyne-RCM reaction of 6aa with Hoveyda–Grubbs’ 1st
generation catalyst in CH2Cl2 at 25 ◦C for 11 h is not superior as
compared to Grubbs’ 1st generation catalyst (Table 2, entry 3).
Surprisingly, it was observed that no products were formed
employing enyne-RCM reaction of 6aa with PtCl2 in C6H5CH3
◦
at 25/85 C for 21 h as shown in Table 2, entries 7 and 8.2f
Interestingly, enyne-RCM reaction of 6aa using Grubbs’ 1st
generation catalyst in CH2Cl2 at 45 ◦C for 5 h furnished the
benzocycloheptene 8aa in 63% yield; but the same reaction at
similar conditions with Grubbs’ 2nd generation catalyst furnished
the 8aa with only 59% yield (Table 2, entries 4 and 6). The optimum
conditions involved the use of 5 mol% Grubbs’ 1st generation
catalyst in enyne-RCM reaction of 6aa in CH2Cl2 at 45 ◦C for 5 h
to furnish 8aa with good yield.
With the optimized reaction conditions in hand, the scope of
the ruthenium-catalyzed enyne-RCM reactions was investigated
322 | Org. Biomol. Chem., 2010, 8, 321–325
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
Table 1 Sequential multi-catalysis cascade approach to the ene-ynes 6/7a
a Yield refers to the column purified products. b Reagents and conditions for Method-A: A mixture of 1a (0.3 mmol), 2 (0.3 mmol) and proline 4 (20 mol%)
in EtOH (0.25 M) was stirred at room temperature for 0.5–11 h. Then o-phenylenediamine (0.3 mmol) and PhCHO (0.3 mmol) were added and stirring
was continued at the same temperature for 1.5–16 h. Then solvent was evaporated and CH2=CHCH2Br (5 equiv.), K2CO3 (8 equiv.) and DMSO (0.25 M)
were added and stirring was continued at the same temperature for 0.25–11 h. c DMSO was used as solvent throughout the reaction sequence. d Reagents
and conditions for Method-B: A mixture of 1a (0.3 mmol), 2 (0.3 mmol), 3a (0.3 mmol) and proline 4 (20 mol%) in EtOH (0.25 M) was stirred at room
temperature for 0.75–24 h. Then solvent was evaporated and CH2=CHCH2Br (5 equiv.), K2CO3 (8 equiv.) and DMSO (0.25 M) were added and stirring
was continued at the same temperature for 0.5–1 h. e Reagents and conditions for Method-C: All reactants 1a, 2h, 3a and catalyst 4 were mixed at the same
time in R-OH a–c and stirred at 25 ◦C, then 15 equiv. of ethereal diazomethane was added and stirred at 25 ◦C for 2–6 h. Then solvent was evaporated
and CH2=CHCH2Br (5 equiv.), K2CO3 (6 equiv.) and DMSO (0.25 M) were added and stirring was continued at the same temperature for 12 h. f 25–30%
of O-allylated (O-A) products 13aj or 13ak are formed. g 50% of O-allylated (O-A) product 13al is formed.
with a variety of functionalized ene-ynes 6/7 as shown in Table 3.
A series of ene-ynes 6 were converted into benzocycloheptenes
8aa–al in moderate to good yields as shown in Table 3. Interest-
ingly, enyne-RCM reaction of diene-yne 6ac using Grubbs’ 1st
generation catalyst (5 mol%) in CH2Cl2 at 45 ◦C for 5 h furnished
the chemoselective product 8ac in 50-60% conversion and 25%
yield (Table 3, entry 3). In a similar manner, selective enyne-RCM
of ene-diyne 6ad using Grubbs’ 1st generation catalyst (5 mol%) in
CH2Cl2 at 45 ◦C for 8 h furnished the chemoselective product 8ad
in 50-60% conversion and 25% yield (Table 3, entry 4). Enyne-
RCM reaction of 1 : 1 dr mixture of chiral (-)-6af furnished
the expected benzocycloheptene (-)-8af in 66% yield with 1 : 1
dr mixture as shown in Table 3, entry 6. Unfortunately, enyne-
RCM reaction on Meldrum’s acid containing ene-yne 6ah didn’t
give the expected product 8ah even after testing at two different
conditions as shown in Table 3, but the similar reaction on
barbituric acid containing ene-yne 6ai furnished the expected
spiro-benzocycloheptene 8ai in moderate yield as shown in Table 3.
Enyne-RCM reaction of cyclic ene-ynes 6aj–al using Grubbs’
1st generation catalyst (5 mol%) in CH2Cl2 at 45 ◦C for 5 h
furnished the spiro-products 8aj–al in 70-83% yields (Table 3,
entries 13–15).
For the rapid high-yielding one-pot synthesis of complex drug-
like molecules and with synthetic/pharmaceutical applications in
mind, we extended the application of amino acid-/self-/K2CO3-/
[Ru]-promoted cascade TCRA/C-A/enyne-RCM products
8aa–al into a novel highly substituted polycyclic substances 11
and 12 through TCRA/C-A/enyne-RCM/DA reaction sequence
(Table 4). Simple acyclic substance, 2-ethynyl-benzaldehyde 1a
was converted into highly functionalized spiro-polycyclic endo-
product 11aja with >99% de in stereoselective manner with
55.9% overall yield through a sequence of amino acid-/self-/
K2CO3-catalyzed cascade TCRA/C-A, ruthenium-promoted
enyne-RCM followed by heat-promoted Diels–Alder (DA)
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 321–325 | 323
©

View Article Online
Table 2 Optimization for enyne-RCM reaction
yield with >99% de, endo-product 12aha2 in 48.75% overall yield
with >99% de, and endo-product 12ahba in 57.0% overall yield
with ≤5% de, respectively as shown in Table 4. Structure and
stereochemistry of polycyclic substances 11–12 were confirmed by
NMR analysis and also by mass analysis. For the pharmaceutical
applications, a diversity-oriented library of polycyclic substances
11/12 could be generated by using our two-step sequential MCC
reactions.
Solvent
Entry Catalyst (5 mol%)
(0.05 M)
T/◦C Time/h Yield (%)a
In a similar manner, 2-ethynyl-benzaldehyde 1a was converted
into highly functionalized spiro tetra-cyclic product 11ajb in
stereospecific manner with 42% overall yield through a sequence
of amino acid-/self-/K2CO3-catalyzed cascade TCRA/C-A, [Ru]-
promoted enyne-RCM followed by heat-promoted Diels–Alder
reaction with diethyl acetylenedicarboxylate 10b in one-pot as
shown in Table 4, entry 4 and generality of this two-step sequential
MCC reactions was further confirmed by two more examples
using different CH-acids 2 and dienophile 10b to furnish the
expected highly functionalized tri-cyclic endo-product 12ahab in
54.0% overall yield with >99% de and endo-product 12ahb2 in 57%
overall yield with ≤5% de, respectively as shown in Table 4, entries
7 and 8. This two-step sequential MCC method will be showing
much impact on the high-yielding synthesis of functionalized
carbocycles.
1
2
Grubbs’ 1st generation CH2Cl2
25
25
14
11
55
55
Grubbs’ 2nd
generation
CH2Cl2
3b
Hoveyda–Grubbs’ 1st CH2Cl2
generation
Grubbs’ 1st generation CH2Cl2
Grubbs ’1st generation PhCH3
25
11
34
4
45
85
45
5
2
7
63
45
59
5b
6
Grubbs’ 2nd
generation
PtCl2
CH2Cl2
7c
8d
PhCH3
PhCH3
25
85
21
21
—
—
PtCl2
a Yield refers to the column purified products. b Reaction conversion is only
50–60%. c Ene-yne 6aa is recovered. d Starting material 6aa is decomposed.
In summary, we have developed the two-step sequential MCC
chemistry for the synthesis of highly substituted drug-like carbocy-
cles 8, 9, 11 and 12 from simple starting materials via TCRA/C-A,
TCRA/A/K/E/C-A, enyne-RCM and Diels–Alder reactions.
The MCC strategy proceeds in good yields with high selectivity
using proline-/self-/K2CO3-/[Ru]-/heat as the catalysts. Further
work is in progress to utilize novel MCC reactions in synthetic
organic chemistry.
reaction with 1-phenyl-pyrrole-2,5-dione 10a in one-pot as shown
in Table 4, entry 1. Generality of the amino acid-/self-/K2CO3-/
[Ru]-/heat-catalyzed stereoselective sequential one-pot cascade
TCRA/C-A or TCRA/A/K/E/C-A, enyne-RCM and DA re-
actions was further confirmed by four more examples using
different CH-acids 2 and dienophile 10a to furnish the expected
highly functionalized polycyclic endo-product 11aka in 32.5%
overall yield with >99% de, endo-product 11ala in 25.0% overall
Table 3 Synthesis of enyne-RCM products 8/9a
a Yield refers to the column purified products. b Reaction conversion is only 50–60%. c Ene-yne 6ah is recovered. d Reaction conditions: PtCl2 (5 mol%),
C6H5CH3 (0.05 M), 110 ◦C, 5 h. e Starting material 6ah is decomposed.
324 | Org. Biomol. Chem., 2010, 8, 321–325
This journal is
The Royal Society of Chemistry 2010
©

View Article Online
Table 4 Rapid one-pot assembly of drug-like polycyclic substances 11/12 from simple acyclic moleculesa
a Yield refers to the column purified products.
Tetrahedron Lett., 2006, 47, 651–656; (b) D. B. Ramachary, M. Kishor
and G. Babul Reddy, Org. Biomol. Chem., 2006, 4, 1641–1646; (c) D. B.
Ramachary and G. Babul Reddy, Org. Biomol. Chem., 2006, 4, 4463–
4468; (d) D. B. Ramachary and M. Kishor, J. Org. Chem., 2007, 72,
5056–5068; (e) D. B. Ramachary, M. Kishor and Y. V. Reddy, Eur. J. Org.
Chem., 2008, 975–998; (f) D. B. Ramachary, Y. V. Reddy and B. V.
Prakash, Org. Biomol. Chem., 2008, 6, 719–726; (g) D. B. Ramachary
and M. Kishor, Org. Biomol. Chem., 2008, 6, 4176–4187; (h) D. B.
Ramachary, Y. V. Reddy and M. Kishor, Org. Biomol. Chem., 2008,
6, 4188–4197; (i) D. B. Ramachary, C. Venkaiah, Y. V. Reddy and M.
Kishor, Org. Biomol. Chem., 2009, 7, 2053–2062; For recent papers on
organocatalytic cascade and multi-component reactions, see: (j) D. B.
Ramachary, K. Ramakumar and V. V. Narayana, J. Org. Chem., 2007,
72, 1458–1463; (k) D. B. Ramachary and R. Sakthidevi, Org. Biomol.
Chem., 2008, 6, 2488–2492; (l) D. B. Ramachary, V. V. Narayana and K.
Ramakumar, Eur. J. Org. Chem., 2008, 3907–3911; (m) D. B. Ramachary,
K. Ramakumar and V. V. Narayana, Chem.–Eur. J., 2008, 14, 9143–
9147; (n) D. B. Ramachary and R. Sakthidevi, Chem.–Eur. J., 2009, 15,
4516–4522; (o) D. B. Ramachary, V. V. Narayana, M. S. Prasad and
K. Ramakumar, Org. Biomol. Chem., 2009, 7, 3372–3378; (p) T. Bui
and C. F. Barbas III, Tetrahedron Lett., 2000, 41, 6951–6954; (q) S.-I.
Watanabe, A. Cordova, F. Tanaka and C. F. Barbas III, Org. Lett., 2002,
4, 4519–4522; (r) N. S. Chowdari, D. B. Ramachary and C. F. Barbas
III, Org. Lett., 2003, 5, 1685–1688; (s) D. B. Ramachary, N. S. Chowdari
and C. F. Barbas III, Angew. Chem., Int. Ed., 2003, 42, 4233–4237;
(t) D. B. Ramachary, K. Anebouselvy, N. S. Chowdari and C. F. Barbas
III, J. Org. Chem., 2004, 69, 5838–5849; (u) D. B. Ramachary and C. F.
Barbas III, Chem.–Eur. J., 2004, 10, 5323–5331; (v) D. B. Ramachary
and C. F. Barbas III, Org. Lett., 2005, 7, 1577–1580; (w) J. W. Yang,
M. T. Hechavarria Fonseca and B. List, J. Am. Chem. Soc., 2005, 127,
15036–15037; (x) Y. Huang, A. M. Walji, C. H. Larsen and D. W. C.
MacMillan, J. Am. Chem. Soc., 2005, 127, 15051–15053; (y) M. Marigo,
T. Schulte, J. Franzen and K. A. Jørgensen, J. Am. Chem. Soc., 2005, 127,
15710–15711; (z) S. Brandau, E. Maerten and K. A. Jorgensen, J. Am.
Chem. Soc., 2006, 128, 14986–14991; (aa) D. Enders, M. R. M. Huettl,
C. Grondal and G. Raabe, Nature, 2006, 441, 861–863; (bb) D. Enders,
M. R. M. Huettl, J. Runsink, G. Raabe and B. Wendt, Angew. Chem., Int.
Ed., 2007, 46, 467–469; (cc) G.-L. Zhao, W.-W. Liao and A. Cordova,
Tetrahedron Lett., 2006, 47, 4929–4932; (dd) R. Rios, H. Sunden, I.
Ibrahem, G.-L. Zhao, L. Eriksson and A. Cordova, Tetrahedron Lett.,
2006, 47, 8547–8551; (ee) W. Wang, H. Li, J. Wang and L. Zu, J. Am.
Chem. Soc., 2006, 128, 10354–10355; (ff) M. Rueping, A. P. Antonchick
and T. Theissmann, Angew. Chem., Int. Ed., 2006, 45, 3683–3686; (gg) H.
Ishikawa, T. Suzuki and Y. Hayashi, Angew. Chem., Int. Ed., 2009, 48,
1304–1307; (hh) D. Zhu, M. Lu, P. J. Chua, B. Tan, F. Wang, X. Yang
and G. Zhong, Org. Lett., 2008, 10, 4585–4588.
Acknowledgements
This work was made possible by a grant from the Department
of Science and Technology (DST), New Delhi [Grant No.:
DST/SR/S1/OC-65/2008]. RM and CV thank CSIR (New
Delhi) for their research fellowships.
Notes and references
1 (a) G. Schneider and U. Fechner, Nat. Rev. Drug Discovery, 2005, 4,
649–663; (b) R. J. Zauhar, G. Moyna, L. Tian, Z. Li and W. J. Welsh,
J. Med. Chem., 2003, 46, 5674–5690; (c) P. Gribbon and A. Sewing,
Drug Discovery Today, 2005, 10, 17–22; (d) T. Honma, Med. Res. Rev.,
2003, 23, 606–632; (e) N. Yoshihiko and I. Akiko, Tetrahedron, 1991, 47,
8985–8990; (f) D. Bailey and D. Brown, Drug Discovery Today, 2001,
6, 57–59; (g) R. S. Bohacek, C. McMartin and W. C. Guida, Med. Res.
Rev., 1996, 16, 3–50.
2 (a) B. M. Trost and M. Lautens, J. Am. Chem. Soc., 1985, 107, 1781–1783;
(b) S. Ma and E.-I. Negishi, J. Org. Chem., 1994, 59, 4730–4732; (c) B. M.
Trost, G. J. Tanoury, M. Lautens, C. Chan and D. T. MacPherson,
J. Am. Chem. Soc., 1994, 116, 4255–4267; (d) S. Ma and E.-I. Negishi,
J. Am. Chem. Soc., 1995, 117, 6345–6357; (e) Y. Yamamoto, Y. Nakagai,
N. Ohkoshi and K. Itoh, J. Am. Chem. Soc., 2001, 123, 6372–6380;
(f) A. M. Echavarren and C. Nevado, Chem. Soc. Rev., 2004, 33, 431–
436; (g) B. L. Ashfeld, K. A. Miller, A. J. Smith, K. Tran and S. F.
Martin, J. Org. Chem., 2007, 72, 9018–9031; (h) F.-X. Felpin and E.
Fouquet, ChemSusChem, 2008, 1, 718–724; (i) C. Kammerer, G. Prestat,
T. Gaillard, D. Madec and G. Poli, Org. Lett., 2008, 10, 405–408; (j) S.
Kotha, A. Chandra Deb and R. Vinod Kumar, Bioorg. Med. Chem.
Lett., 2005, 15, 1039–1043; (k) K. C. Nicolaou, D. J. Edmonds and P. G.
Bulger, Angew. Chem., Int. Ed., 2006, 45, 7134–7186; (l) K. C. Nicolaou
and J. S. Chen, Chem. Soc. Rev., 2009, 38, 2993–3009.
3 For review articles, see: (a) S. K. Chattopadhyay, S. Karmakar, T. Biswas,
K. C. Majumdar, H. Rahman and B. Roy, Tetrahedron, 2007, 63, 3919–
3952; (b) A. Michaut and J. Rodriguez, Angew. Chem., Int. Ed., 2006,
45, 5740–5750; (c) A. Gradillas and J. Perez-Castells, Angew. Chem.,
Int. Ed., 2006, 45, 6086–6101; (d) A. Deiters and S. F. Martin, Chem.
Rev., 2004, 104, 2199–2238; (e) M. D. McReynolds, J. M. Dougherty and
P. R. Hanson, Chem. Rev., 2004, 104, 2239–2258; (f) A. Furstner, Angew.
Chem., Int. Ed., 2000, 39, 3012–3043; (g) T. M. Trnka and R. H. Grubbs,
Acc. Chem. Res., 2001, 34, 18–29; (h) K. Sambasivarao, M. Milind and
T. Arti, Chem. Soc. Rev., 2009, 38, 2065–2092.
4 For recent papers on organocatalytic TCRA reactions for C–C bond
formation, see: (a) D. B. Ramachary, M. Kishor and K. Ramakumar,
This journal is
The Royal Society of Chemistry 2010
Org. Biomol. Chem., 2010, 8, 321–325 | 325
©