An efficient protocol of indium-catalyzed allylic substitution reaction and its application to polymer synthesis: Complementary regio- and stereoselective allylation polycondensation via Ir and Pd catalyses

Article abstract of DOI:10.1021/ja076019k

An efficient protocol of the Ir-catalyzed allylic substitution reaction is reported using N,O-bis(trimethylsilyl)acetamide as a base in the presence of nBu₄NF as a cocatalyst. The reaction completely proceeded under very mild conditions, and a branched allylated compound that is not easy to access via the Tsuji-Trost reaction can be synthesized. The reaction system is practical enough to be applicable for polymer syntheses. The Ir- and Pd-catalyzed allylation polycondensations generally show complementary regio- and stereoselectivities. The Ir-catalyzed reaction is versatile, and a mixed dual regioselectivity such as a branched-linear selectivity on each electrophile can also be achieved. Copyright

Full text of DOI:10.1021/ja076019k

Published on Web 01/01/2008
An Efficient Protocol of Iridium-Catalyzed Allylic Substitution Reaction and Its
Application to Polymer Synthesis: Complementary Regio- and
Stereoselective Allylation Polycondensation via Ir and Pd Catalyses
Nobuyoshi Nomura,* Susumu Komiyama, Hiroyuki Kasugai, and Marie Saba
Laboratory of Polymer Chemistry, Graduate School of Bioagricultural Sciences, Nagoya UniVersity,
Nagoya 464-8601, Japan
Received August 10, 2007; E-mail: nnomura@nagoya-u.jp
Table 1. Ir-Catalyzed Regioselective Allylic Substitution Reactiona
The development of regio- and stereoselective polymeri-
zations continues to be an important topic1 because these selectivi-
ties are fundamental elements that determine the properties of a
polymeric material. For the synthesis of polymers whose main
chains consist of only C-C bonds, vinyl polymerizations have
arguably dominated2 the polymeric materials in our daily
life. However, there are crucial drawbacks in the vinyl polymeriza-
tions, for example, a limitation of only two carbons as the repeating
unit in the main chain and loss of the double bond in every
monomer. Under such circumstances, a regioselective C-C bond-
forming allylation polycondensation via the Tsuji-Trost reaction3
(TTR) was developed4,5 (eq 1a), and a Pd-catalyzed polyconden-
sation that proceeds without strict stoichiometric balance was
realized in certain cases.6 A characteristic of this polycondensation
a Reaction conditions: allylic ester, 0.50 mmol; MeCH(CO2Et)2, 90 µL
is that a new C-C bond is formed between the sp3-hybridized
(0.52 mmol), [IrCl(COD)]2, 3.3 mg (4.9 µmol); 1 M nBu4NF in THF, 0.050
carbons (Csp3’s) of the monomers without losing the double bond
of the allylic monomer. Although transition metal-catalyzed ally-
lation reactions7,8 whose major products are not easily accessible
via the TTR have been reported,9-12 they have not been applied in
polymer synthesis. This is due to the severe limitations of the
polycondensation reaction.13 We now report an efficient protocol
of the Ir-catalyzed allylic substitution reaction, which we may call
the “Takeuchi reaction”,12 and its applications in polymer synthesis14
(eq 1b). This Ir-catalyzed regio- and stereoselective polyconden-
sation can fill in some of the methodological gaps of the polym-
erization via the TTR.
mL (0.050 mmol); BSA, 0.37 mL (1.5 mmol); toluene, 1.0 mL. b 2 mol %.
c Isolated yield after column chromatography. d The branched/linear (B/L)
ratio of the products and the E/Z ratio (%) of the linear product were
determined by GC. e Allylic substrate 2 remained after 4 h (7% by 1H NMR).
f The Z-isomer was not detectable/separable by GC.
4°-carbon were obtained in excellent yields. Cinnamyl ben-
zoate 1 was superior to the corresponding acetate ester (99% yield,
B/L ) 86/14) regarding the regioselectivity (entry 1). The addition
of P(OPh)3 improved the branched regioselectivity as expected12a,c,e
(entry 2). To our surprise, PPh3 was superior to P(OPh)3 based on
the regioselectivity (entry 3). As far as we know, this is the first
Ir-catalyzed allylic substitution reaction system where PPh3 showed
a higher branched regioselectivity than P(OPh)3. Branched substrate
2 also selectively afforded the branched product (entries 4 and 5).
On the other hand, linear alkyl-substituted 3 selectively gave a linear
product (entry 6). In contrast, branched 4, which was an allylic
isomer of 3, selectively afforded the branched product (entries 7
and 8). For this electrophile, PPh3 slightly decreased the regiose-
lectivity.
This efficient protocol synthesizing the branched products was
In spite of extensive studies of the Ir-catalyzed allylic substitution
reaction,12 the quantitative formation of quaternary (4°-) carbon
centers with a branched selectivity by the Ir catalysis has been
hardly studied.15 N,O-Bis(trimethylsilyl)acetamide16 (BSA) has
rarely been utilized in the Ir-catalyzed C-C bond-forming allylic
substitution reaction,17,18 although it is an excellent reagent
in the TTR3 and the polycondensation via the TTR.4 No reaction
occurred between cinnamyl acetate and commercially available
diethyl methylmalonate (MeCHE2, E ) CO2Et) in CH2Cl2
similar to the conditions of the Pd system.5a By examination of
the reaction conditions, non-halogenated solvents such as toluene
and THF were suitable, and a catalytic amount of nBu4NF (TBAF)
(10 mol %) smoothly promoted the reaction. The scope is presented
in Table 1. Nearly 1 equiv of MeCHE2 (1.05 equiv) was sufficient
to complete the reaction in a short time, and the products with a
applicable to the regio- and stereoselective Csp3-Csp3 bond-
forming polycondensation. Table
2 illustrates the comple-
mentary regio- and stereoselective polycondensations catalyzed by
Ir and Pd. In the absence of ligands, precipitation due to metal
aggregation was observed when the reaction time increased, so that
PPh3 as a ligand was added to the Ir-catalyzed allylation
polycondensation reaction to keep the reaction homogeneous.
Electrophile 5 and nucleophile 6 afforded branched and linear
polymers when using the Ir and Pd catalysts, respectively (entry
1). Electrophile 7 produced results consistent with those of its allylic
isomer 5 (entry 2). The branched electrophile 8, in which
two branched allylic moieties were connected to a trimethylene
group, also gave the expected branched and linear polymers
using each catalyst (entry 3). The regioselectivity of the Ir catalyst
9
812
J. AM. CHEM. SOC. 2008, 130, 812-814
10.1021/ja076019k CCC: $40.75 © 2008 American Chemical Society

C O M M U N I C A T I O N S
Table 2. Complementary Regio- and Stereoselective Ir- and Pd-Catalyzed Allylation Polycondensationa
a Polymerization conditions unless otherwise noted: allylic substrate, 0.50 mmol; nucleophile, 0.50 mmol; catalyst 5 µmol; PPh3 for Ir catalyst or
bis(diphenylphosphino)butane for Pd catalyst, 10 µmol); BSA, 3.0 mmol; toluene (Ir) or CH2Cl2 (Pd), 1.0 mL; 25 °C for Ir catalyst or 40 °C for Pd catalyst.
nBu4NF (1 M in THF, 50 µL, 50 µmol) was added to the Ir system. The polymerization was traced by SEC analysis of the crude reaction mixture. b The
branched/linear ratio by 1H NMR. c Mn, number-average molecular weight of the crude product by size-exclusion chromatography (SEC, polystyrene standards,
CHCl3, 40 °C); Mw/Mn, polydispersity index of the crude product by SEC. All of the values of Mn and Mw/Mn were consistent after purification. d Purified
by gel filtration (Sephadex LH-60, MeOH/CHCl3 ) 2/1). e Data using a corresponding acetate as an electrophile (E′ ) CO2Et); see ref 5a. f Reaction temp,
60 °C. g The polymerization time was not optimized.
(B/L ) 91/9) was higher than the one in the model reaction
(entry 8, Table 1), and it may be caused by intramolecular
coordination of the vinyl group to the Ir catalyst.19 The stereo-
selectivity of the polymer using the Pd catalyst was high, and no
Z-olefin was detected by 1H NMR. The polycondensation between
9 and 6 using the Ir catalyst proceeded in a regio- and stereoselective
manner, and a linear Z-selective polyether was obtained without
any problems in the presence of an etheral oxygen atom close to
the reaction sites (entry 4, Ir). On the other hand, the polyconden-
sation using the Pd catalyst afforded a linear E-selective polyether
(entry 4, Pd). Both the Ir and Pd catalysts showed a linear
regioselectivity toward the Z-electrophile, and the E/Z stereo-
selectivity was complementary. Simple CH2(CO2Me)2 (10) also
worked as a monomer, and a corresponding polyether was
obtained (entry 5). The polycondensation of 5 with 10 using the Ir
catalyst produced a rather lower regioselectivity (B/L ) 76/24, entry
6, Ir), which was expected due to formation of the ex-
tremely congested 3°-4°-3°-carbon linkages by a doubly branched
regioselectivity. On the basis of the model reactions of 1-CH2(CO2-
Me)2 (eq 2) and entry 3 in Table 1, less than 1% (5% × 0.05) of
the linear-linear linkage was formed. Hence, the B/L ratio (B/L )
76/24) indicated that the ratio of B,B/B,L repeating units was 52/
48. Although we were surprised at the 52% formation of this
congested linkage, it was also notable that nearly half of the polymer
linkages (48%) were branched-linear on each nucleophile
(entry 6, Ir). The Pd-catalyzed polycondensation gave the corre-
sponding linear polymer with a high regioselectivity (entry 6, Pd).
An interesting dual regioselectivity on each electrophile was
achieved by the Ir catalyst (entry 7, Ir). The dramatic effects of the
ortho-substituents were observed on electrophile 11, and the
polycondensation of 11 with 6 was slow at 25 °C. Although
the obtained polymer surprisingly appeared to show no
regioselectivity, the model reaction of eq 3 provided us with
Scheme 1. A Dual Regioselectivity on Electrophile 11
information about a regular repeating unit of the polymer
structure.
In eq 3, only a trace amount of the linear-linear product (<1%)
and no branched-branched product were detected in the crude
1
reaction mixture by H NMR, and two products were isolated in
high yields. The regioselectivity of eq 3 is explained as shown in
Scheme 1. The first allylation of 11 preferentially occurred with
the branched regioselectivity on the basis of entry 3 of Table 1.
The second allylation then occurred with an exclusive linear
selectivity because the branched-branched product was not detected
in eq 3. When the linear product was afforded by the first allylation,
9
J. AM. CHEM. SOC. VOL. 130, NO. 3, 2008 813

C O M M U N I C A T I O N S
Asymmetry 1992, 3, 1089. (e) Trost, B. M. Chem. Pharm. Bull. 2002, 50,
1. (f) Tsuji, J. J. Synth. Org. Chem. Jpn. 1999, 57, 1036. (g) Helmchen,
G. In PerspectiVes in Organopalladium Chemistry for the XXI Century;
Tsuji, J., Ed.; Elsevier: Lausanne, Switzerland, 1999; pp 203-214.
(4) Reviews: (a) Suzuki, M. J. Synth. Org. Chem. Jpn. 1993, 51, 141. (b)
Nomura, N.; Tsurugi, K.; Yoshida, N.; Okada, M. Curr. Org. Synth. 2005,
2, 21. (c) Nomura, N.; Tsurugi, K.; Yoshida, N.; Komiyama, S.; Okada,
M. J. Synth. Org. Chem. Jpn. 2007, 65, 334.
(5) (a) Nomura, N.; Tsurugi, K.; Okada, M. J. Am. Chem. Soc. 1999, 121,
7268. (b) Nomura, N.; Yoshida, N.; Tsurugi, K.; Aoi, K. Macromolecules
2003, 36, 3007.
(6) (a) Nomura, N.; Tsurugi, K.; Okada, M. Angew. Chem., Int. Ed. 2001,
40, 1932. (b) Tsurugi, K.; Nomura, N.; Aoi, K. Tetrahedron Lett. 2002,
43, 469. (c) Nomura, N.; Tsurugi, K.; RajanBabu, T. V.; Kondo, T. J.
Am. Chem. Soc. 2004, 126, 5354.
(7) Reviews: (a) Takeuchi, R. Polyhedron 2000, 19, 557. (b) Takeuchi, R.
Synlett 2002, 1954. (c) Helmchen, G.; Dahnz, A.; Du¨bon, P.; Schelwies,
M.; Weihofen, R. Chem. Commun. 2007, 675. (d) Takeuchi, R.; Kezuka,
S. J. Synth. Org. Chem. Jpn. 2007, 65, 652. (e) See refs 3.
(8) Studies of Pd: (a) Pamies, O.; Die´guez, M.; Claver, C. J. Am. Chem.
Soc. 2005, 127, 3646. (b) Faller, J. W.; Wilt, J. C. Org. Lett. 2005, 7,
633. (c) Zheng, W.-H.; Zheng, B.-H.; Zhang, Y.; Hou, X.-L. J. Am. Chem.
Soc. 2007, 129, 7718. (d) Acemoglu, L.; Williams, J. M. J. AdV. Synth.
Catal. 2001, 343, 75.
(9) Studies of Mo: (a) Trost, B. M.; Hachiya, I. J. Am. Chem. Soc. 1998,
120, 1104. (b) Trost, B. M.; Hildbrand, S.; Dogra, K. J. Am. Chem. Soc.
1999, 121, 10416. (c) Glorius, F.; Neuburger, M.; Pfaltz, A. HelV. Chim.
Acta 2001, 84, 3178. (d) Kaiser, N.-F. K.; Bremberg, U.; Larhed, M.;
Moberg, C.; Hallberg, A. Angew. Chem., Int. Ed. 2000, 39, 3596. (e) Trost,
B. M.; Dogra, K. J. Am. Chem. Soc. 2002, 124, 7256.
the second reaction showed the branched regioselectivity due to
the lack of the bulky malonic ester around the second reaction site.
After all, branched-linear regioselectivity (>99%) was achieved
on each electrophile. Therefore, we concluded that the regular
polymer with a branched-linear regioselectivity on each electro-
phile was obtained by a single Ir catalyst. The ortho-substitution
also brought the effects on the regioselectivity by Pd catalysis. The
polymer via the TTR had a highly linear-linear structure as the
repeating unit (B/L < 1/99, entry 7, Pd). Since the regioselectivity
of the polymerization between 5 and 6 was B/L ) 6/94 (entry 1,
Pd), the exclusive regioselectivity in the polycondensation should
also come from the effects of the ortho-substitution.
The vinyl groups20 of the polymer can be functionalized. As an
example, the polymer synthesized in entry 1 of Table 2, Ir, was
reacted with m-chloroperbenzoic acid (mCPBA, 2 equiv to the
olefin). Although an efficient purification method is still under
investigation, the vinyl groups were converted into the oxirane
groups (vinyl/oxirane ) 1/9, eq 4).21
(10) Studies of W: (a) Lloyd-Jones, G. C.; Pfaltz, A. Angew. Chem., Int. Ed.
Engl. 1995, 34, 462. (b) Trost, B. M.; Tometzki, G. B.; Hung, M.-H. J.
Am. Chem. Soc. 1987, 109, 2176.
(11) Studies of Rh: (a) Evans, P. A.; Nelson, J. D. J. Am. Chem. Soc. 1998,
120, 5581. (b) Evans, P. A.; Kennedy, L. J. J. Am. Chem. Soc. 2001, 123,
1234. (c) Evans, P. A.; Robinson, J. E. J. Am. Chem. Soc. 2001, 123,
4609.
In conclusion, we reported the efficient protocol of the Ir-
catalyzed allylic substitution reaction to form a 4°-carbon with a
branched regioselectivity. The high efficiency was documented by
applications to polycondensation, in which a nearly complete
conversion of the functional groups under a strict stoichiometric
balance is generally required. Various polymer structures from the
same monomers can now be arranged using either the Ir or Pd
catalyst. Further studies of other monomers and the obtained
polymer properties are now in progress.
(12) Studies of Ir: (a) Takeuchi, R.; Kashio, M. Angew. Chem., Int. Ed. Engl.
1997, 36, 263. (b) Janssen, J. P.; Helmchen, G. Tetrahedron Lett. 1997,
38, 8025. (c) Takeuchi, R.; Kashio, M. J. Am. Chem. Soc. 1998, 120,
8647. (d) Bartels, B.; Helmchen, G. Chem. Commun. 1999, 741. (e)
Bartels, B.; Garc´ıa-Yebra, C.; Rominger, F.; Helmchen, G. Eur. J. Inorg.
Chem. 2002, 2569. (f) Bartels, B.; Garc´ıa-Yebra, C.; Helmchen, G. Eur.
J. Org. Chem. 2003, 1097. (g) Lipowsky, G.; Miller, N.; Helmchen, G.
Angew. Chem., Int. Ed. 2004, 43, 4595. (h) Streiff, S.; Welter, C.;
Schelwies, M.; Lipowsky, G.; Miller, N.; Helmchen, G. Chem. Commun.
2005, 2957. (i) Graening, T.; Hartwig, J. F. J. Am. Chem. Soc. 2005, 127,
17192. (j) Schelwies, M.; Du¨bon, P.; Helmchen, G. Angew. Chem., Int.
Ed. 2006, 45, 2466. (k) Weix, D. J.; Hartwig, J. F. J. Am. Chem. Soc.
2007, 129, 7720. (l) Polet, D.; Alexakis, A. Org. Lett. 2005, 7, 1621. (m)
Polet, D.; Alexakis, A.; Tissot-Croset, K.; Corminboeuf, C.; Ditrich, K.
Chem.sEur. J. 2006, 12, 3596.
Acknowledgment. We thank Professor Tadao Kondo for his
continuous encouragement and support of this study. This study
was partially supported by the Asahi Glass Foundation.
(13) (a) Carothers, W. H. Trans. Faraday Soc. 1936, 32, 39. (b) Flory, P. J. J.
Am. Chem. Soc. 1936, 58, 1877. (c) Flory, P. J. Chem. ReV. 1946, 39,
137. (d) See refs 4b,c.
(14) Part of this study was presented at SPSJ Meetings: (a) Nomura, N.;
Komiyama, S.; Saba, M.; Kondo, T. Polym. Prepr., Jpn. Symp. Macromol.
2005, 54, 2Pd006. (b) Komiyama, S.; Nomura, N.; Saba, M.; Kondo, T.
Polym. Prepr., Jpn. Annu. Meet. 2006, 55, 2D01. (c) Nomura, N.;
Komiyama, S.; Saba, M.; Kondo, T. Polym. Prepr., Jpn. Macromol. Symp.
2006, 55, 2Pb006.
(15) Takeuchi et al. reported that MeCH(CO2Et)2 gave a linear regioselectivity
in the Ir-catalyzed allylic substitution reaction in some cases (ref 12c).
See also refs 12h and 12m for quaternary carbon formations by Ir-catalyzed
allylic substitution.
Supporting Information Available: Experimental procedures,
NMR data (1H and 13C) of polymers by the Ir catalyst, and function-
alization of the polymer with mCPBA. This material is available free
of charge via the Internet at http://pubs.acs.org.
References
(1) Some recent studies of regio- and/or stereoselective C-C bond-forming
polymerization: (a) Takeuchi, D.; Matsuura, R.; Park, S.; Osakada, K. J.
Am. Chem. Soc. 2007, 129, 7002. (b) Okada, T.; Park, S.; Takeuchi, D.;
Osakada, K. Angew. Chem., Int. Ed. 2007, 46, 6141. (c) Motta, A.; Fragala,
I. L.; Marks, T. J. J. Am. Chem. Soc. 2007, 129, 7327. (d) Miura, Y.;
Shibata, T.; Satoh, K.; Kamigaito, M.; Okamoto, Y. J. Am. Chem. Soc.
2006, 128, 16026. (e) Peretti, K. L.; Ajiro, H.; Cohen, C. T.; Lobkovsky,
E. B.; Coates, G. W. J. Am. Chem. Soc. 2005, 127, 11566. (f) Takeuchi,
D.; Anada, K.; Osakada, K. Angew. Chem., Int. Ed. 2004, 43, 1233. (g)
Takeuchi, D.; Osakada, K. Chem. Commun. 2002 646. (h) Takeuchi, D.;
Anada, K.; Osakada, K. Macromolecules 2002, 35, 9628. (i) Takeuchi,
D.; Kim, S.; Osakada, K. Angew. Chem., Int. Ed. 2001, 40, 2685. (j) Isobe,
Y.; Fujioka, D.; Habaue, S.; Okamoto, Y. J. Am. Chem. Soc. 2001, 123,
7180.
(2) (a) Ihara, E. Kobunshi 2007, 56, 34. (b) Webster, O. W.; Hertler, W. R.;
Sogah, D. Y.; Farnham, W. B.; RajanBabu, T. V. J. Am. Chem. Soc. 1983,
105, 5706. (c) Webster, O. W. J. Polym. Sci., Part A: Polym. Chem.
2000, 38, 2855.
(3) Reviews: (a) Trost, B. M.; Crawley, M. L. Chem. ReV. 2003, 103, 2921.
(b) Tsuji, J. Transition Metal Reagents and Catalysts, InnoVations in
Organic Synthesis; John Wiley: Chichester, UK, 2000; Chapter 4, pp
109-168. (c) Trost, B. M.; Van Vranken, D. L. Chem. ReV. 1996, 96,
395. (d) Frost, C. G.; Howarth, J.; Williams, J. M. J. Tetrahedron:
(16) A review of BSA: El Gihani, M. T.; Heaney, H. Synthesis 1998, 357.
(17) In ref 12e, Helmchen et al. reported that BSA was not effective for the
C-C bond-forming allylic substitution in the presence of a catalytic
amount of KOAc (5 days, 13% yield).
(18) (a) To the best of our knowledge, Alexakis reported the first practical
C-C bond formation using BSA in the Ir-catalyzed allylic substitution
(ref 12m). In their system, a catalytic amount of KOAc was added. Very
recently, Hamada reported another system using BSA in the presence of
catalytic amounts of LiOAc and NaPF6: Nemoto, T.; Sakamoto, T.;
Fukuyama, T.; Hamada, Y. Tetrahedron Lett. 2007, 48, 4977. (b) C-N
bond formation: Nemoto, T.; Sakamoto, T.; Matsumoto, T.; Hamada, Y.
Tetrahedron Lett. 2006, 47, 8737.
(19) (a) Devasagayaraj, A.; Stu¨demann, T.; Knochel, P. Angew. Chem., Int.
Ed. Engl. 1996, 34, 2723. (b) Krafft, M. E.; Sugiura, M.; Abboud, K. A.
J. Am. Chem. Soc. 2001, 123, 9174. (c) Miller, K. M.; Jamison, T. F. J.
Am. Chem. Soc. 2004, 126, 15342. (d) Moslin, R. A.; Miller, K. M.;
Jamison, T. F. Tetrahedron 2006, 62, 7598.
(20) Recent syntheses of polymers with pendant vinyl groups: (a) Jeske, R.
C.; DiCiccio, A. M.; Coates, G. W. J. Am. Chem. Soc. 2007, 129, 11330.
(b) Bertini, F.; Canetti, M.; Ricci, G. J. Appl. Polym. Sci. 2004, 92, 1680.
(21) See the Supporting Information for details.
JA076019K
9
814 J. AM. CHEM. SOC. VOL. 130, NO. 3, 2008