Rh-catalyzed Negishi alkyl-aryl cross-coupling leading to α- or β-phosphoryl-substituted alkylarenes

Article abstract of DOI:10.1021/jo900142b

The catalytic cross-coupling between ArZnX and ICH₂(CH ₂)_nP(O)(OEt)₂ (n = 0-3) has been investigated to determine the utility of the Rh catalyst during the alkyl-aryl cross-coupling and to develop a new syntheti

Full text of DOI:10.1021/jo900142b

Rh-Catalyzed Negishi Alkyl-Aryl Cross-Coupling Leading to r- or
ꢀ-Phosphoryl-Substituted Alkylarenes
Hideki Takahashi, Shinya Inagaki, Naoko Yoshii, Fuxing Gao, Yasushi Nishihara, and
Kentaro Takagi*
Department of Chemistry, Faculty of Science, Okayama UniVersity, Tsushima, Okayama 700-8530, Japan
takagi@cc.okayama-u.ac.jp
ReceiVed January 22, 2009
The catalytic cross-coupling between ArZnX and ICH2(CH2)nP(O)(OEt)2 (n ) 0-3) has been investigated
to determine the utility of the Rh catalyst during the alkyl-aryl cross-coupling and to develop a new
synthetic method for phosphoryl-substituted alkylarenes. Rh-dppf exhibits an excellent catalytic activity
for the reaction with the alkylphosphonate of n ) 1, whereas for the reaction with those of n ) 2 or 3,
ꢀ-hydride elimination mainly takes place. As for the reaction with an alkylphosphonate of n ) 0, a
polarity inversion of the coupling components is necessary in order to provide the coupling products; the
phosphoryl analogue of the Reformatsky reagent and ArI give the cross-coupling products in good yields
through the catalysis by Rh-dppf.
Introduction
The Pd- or Ni-catalyzed cross-coupling of carbon electro-
philes, R-X, with organometallic compounds, R′-m, is one of
the most useful methods for constructing carbon-carbon bonds
in organic synthesis.1 Various kinds of coupling components
such as aryl, alkenyl, alkynyl, and alkyl electrophiles and
nucleophiles are applicable for this reaction; however, alkyl
electrophiles, R ) alkyl, are generally unsuitable because of
the readily occurring side reaction, ꢀ-hydride elimination, under
the catalytic conditions,2 except for the activated ones containing
functional groups such as R ) CH2CO2Et at the R-position.3
Recently, the incidental drawbacks using conventional Pd or
Ni catalysis have been overcome by using novel auxiliary
components of the catalysts such as bulky and electron-rich
phosphines,4 chelating diamines,5 N-heterocyclic carbenes,6 1,3-
alkadienes,7 or electron-poor alkenes,8 which even allow the
FIGURE 1. Alkyl-aryl cross-coupling: Pd or Ni catalysis versus Rh
catalysis.
reactions with arylmetallic compounds, R′ ) Ar, belonging to
the relatively weak nucleophiles in the cross-coupling reactions2a
(Figure 1). Furthermore, in certain instances, the catalysis is
reported to be compatible with reactive functional groups such
as an ester, ketone, nitrile, amide, or sulfoxide at carbons other
than at the R-position of the alkyl chains,4a,b,d-f,5b,6,8 thus
expanding the synthetic utility of the reaction. During the course
of our study of the catalytic efficiency of Rh in the Negishi
(1) For reviews, see: (a) Metal-Catalyzed Cross-Coupling Reactions; Dieder-
ich, F., Stang, P. J., Eds.; Wiley-VCH: Weinheim, 1998. (b) Handbook of
Organopalladium Chemistry for Organic Synthesis; Negishi, E., Ed.; John Wiley
& Sons: New York, 2002. (c) Tsuji, J. Palladium Reagents and Catalysis:
InnoVation in Organic Synthesis; John Wiley & Sons: New York, 1995.
(2) (a) Frisch, A. C.; Beller, M. Angew. Chem., Int. Ed. 2005, 44, 674–688.
(b) Luh, T.-Y.; Leung, M.-K.; Wong, K.-T. Chem. ReV. 2000, 100, 3187–3204.
(3) (a) Klingstedt, T.; Frejd, T. Organometallics 1983, 2, 598–600. (b)
Simpson, J. H.; Stille, J. K. J. Org. Chem. 1985, 50, 1759–1760. (c) Amano, T.;
Yoshikawa, K.; Sano, T.; Ohuchi, Y.; Shiono, M.; Ishiguro, M.; Fujita, Y. Synth.
Commun. 1986, 16, 499–507. (d) Sato, M.; Miyaura, N.; Suzuki, A. Chem. Lett.
1989, 1405–1408.
(4) (a) Frisch, A. C.; Shaikh, N.; Zapf, A.; Beller, M. Angew. Chem., Int.
Ed. 2002, 41, 4056–4059. (b) Kirchhoff, J. H.; Netherton, M. R.; Hills, I. D.;
Fu, G. C. J. Am. Chem. Soc. 2002, 124, 13662–13663. (c) Lee, J.-Y.; Fu, G. C.
J. Am. Chem. Soc. 2003, 125, 5616–5617. (d) Tang, H.; Menzel, K.; Fu, G. C.
Angew. Chem., Int. Ed. 2003, 42, 5079–5082. (e) Zhou, J.; Fu, G. C. J. Am.
Chem. Soc. 2003, 125, 12527–12530. (f) Brenstrum, T.; Gerristma, D. A.;
Adjabeng, G. M.; Frampton, C. S.; Britten, J.; Robertson, A. J.; McNulty, J.;
Capretta, A. J. Org. Chem. 2004, 69, 7635–7639.
2794 J. Org. Chem. 2009, 74, 2794–2797
10.1021/jo900142b CCC: $40.75 2009 American Chemical Society
Published on Web 03/06/2009

R- or ꢀ-Phosphoryl-Substituted Alkylarenes
TABLE 1. Effect of Catalyst in Cross-Coupling between 1a and 2a
reaction, we found another methodology to achieve the alkyl-
aryl cross-coupling with nonactiVated alkyl electrophiles.9 That
is, in our reaction, it is not the auxiliary components of the
catalysts but both the utility of the Rh as a catalyst and the
manipulation of the coupling components by introduction of
carbonyl groups near the reaction centers that could significantly
suppress the ꢀ-hydride elimination. In this investigation, we
studied the effect of phosphoryl groups on the alkyl-coupling
partners during the Rh-catalyzed alkyl-aryl cross-coupling,
intending to develop a new synthetic method for phosphoryl-
substituted alkylarenes, a useful class of compounds in such
fields as synthetic organic chemistry, represented by their utility
as intermediates of the Horner-Wadsworth-Emmons reac-
tion,10 medicinal chemistry,11 etc.12
entry
catalyst
time (h)
yieldb (%)
1
2
3
4
1/2[RhCl(cod)]2/dppf
1/2[RhCl(cod)]2/dppf
1/2[RhCl(cod)]2/BINAP
1/2[RhCl(cod)]2/PPh3
1/2[RhCl(cod)]2/dppp
1/2[RhCl(cod)]2/dppf
1/2[RhCl(cod)]2/dppf
Pd(PPh3)4
1
20
20
1
1
1
20
20
20
20
91
92
70
<5
39
92
39
<5
<5
14
5
6c
7d
8
9
10
PdCl2(dppf)
NiCl2(dppf)
a 1a (0.56 mmol), 2 (0.4 mmol), catalyst (0.02 mmol), and THF (0.47
mL) were employed for all entries, except for entry 2, where 0.008
mmol of catalyst was used. b GLC yield. c TMU was used as solvent.
d BrCH2CH2P(O)(OEt)2 4 was used in place of 2.
Results and Discussion
A reaction solution composed of phenylzinc iodide (1a; 1.4
equiv), diethyl 2-iodoethylphosphonate (2; 1.0 equiv), and a Rh
catalyst (2-5 mol %) in THF was stirred at 40 °C under nitrogen
(Table 1). Throughout this study, the Rh catalysts were prepared
in situ from [RhCl(cod)]2 (cod ) 1,5-cyclooctadiene) and
various phosphorus ligands (Rh/P ) 1:2), among which Rh-
dppf (dppf ) 1,1′-bis(diphenylphosphino)ferrocene) exhibited
an excellent catalytic activity in the reaction, giving the desired
coupling product 3a in high yield (entries 1 and 2). Rh-BINAP
was also effective for the reaction but required a longer reaction
time than Rh-dppf (entry 3). On the other hand, Rh-PPh3 and
Rh-dppp (dppp ) 1,3-bis(diphenylphosphino)propane) gave 3a
in low yields, though both starting materials 1a and 2 were
completely consumed under the stated conditions (entries 4 and
5). As the reaction solvent, TMU (TMU ) N,N,N′,N′-tetram-
ethylurea) was effective as THF (entry 6), but the reactivity of
the bromide 4 was lower than 2 (entry 7). For the same reaction,
the conventional Pd or Ni catalysts were far less effective than
Rh-dppf, even if dppf was used as a ligand (entries 8-10),
underlining the striking utility of Rh in the reaction.9,13 To the
best of our knowledge, this is the first example of synthesizing
the phosphoryl substituted alkylarenes by the catalytic alkyl-
aryl cross-coupling with nonactivated alkyl electrophiles.14
Various arylzinc compounds containing such functional groups
as CH3 (entry 2), OCH3 (entry 3), Cl (entry 4), or CO2R (entries
5 and 6) at the para or meta position, 1b-f, underwent catalysis
by Rh-dppf during the reaction with 2 to afford the correspond-
ing coupling products 3b-f in good isolated yields, as shown
in Table 2, whereas the substituent groups at the ortho position,
1g and 1h, completely inhibited the desired cross-coupling
(entries 7 and 8).
(5) (a) Zhou, J.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 1340–1341. (b)
Powell, D. A.; Fu, G. C. J. Am. Chem. Soc. 2004, 126, 7788–7789.
(6) Frisch, A. C.; Rataboul, F.; Zapf, A.; Beller, M. J. Organomet. Chem.
2003, 687, 403–409.
(7) (a) Terao, J.; Watanabe, H.; Ikumi, A.; Kuniyasu, H.; Kambe, N. J. Am.
Chem. Soc. 2002, 124, 4222–4223. (b) Terao, J.; Todo, H.; Watanabe, H.; Ikumi,
A.; Kambe, N. Angew. Chem., Int. Ed. 2004, 43, 6180–6182.
(8) (a) Giovannini, R.; Knochel, P. J. Am. Chem. Soc. 1998, 120, 11186–
11187. See also: (b) Giovannini, R.; Stu¨demann, T.; Dussin, G.; Knochel, P.
Angew. Chem., Int. Ed. 1998, 37, 2387–2390.
(9) (a) Takahashi, H.; Inagaki, S.; Nishihara, S.; Shibata, T.; Takagi, K. Org.
Lett. 2006, 3037–3040. See also: (b) Hossain, K. M.; Takagi, K. Chem. Lett.
1999, 1241–1242. (c) Takahashi, H.; Hossain, K. M.; Nishihara, Y.; Shibata,
T.; Takagi, K. J. Org. Chem. 2006, 71, 671–675.
(10) See for example: (a) Cai, C.; Liakatas, I.; Wong, M.-S.; Boesch, M.;
Bosshard, C.; Guenter, P.; Concilio, S.; Tirelli, N.; Suter, U. W. Org. Lett. 1999,
1, 1847–1849. (b) D.-Barra, E.; G.-Martinez, J. C.; R.-Lopez, J. Tetrahedron
Lett. 1999, 40, 8181–8184. (c) Brunner, H.; Le Cousturier de Courcy, N.; Genet,
J.-P. Synlett 2000, 201–204. (d) Lindner, E.; Khanfar, M. J. Organomet. Chem.
2001, 630, 244–252. (e) Kawano, T.; Kato, T.; Du, C.-X.; Ueda, I. Tetrahedron
Lett. 2002, 43, 6697–6700. (f) Cho, B. R.; Chajara, K.; Oh, H. J.; Son, K. H.;
Jeon, S.-J. Org. Lett. 2002, 4, 1703–1706. (g) Zheng, S.; Barlow, S.; Parker,
T. C.; Marder, S. R. Tetrahedron Lett. 2003, 44, 7989–7992. (h) Azzena, U.;
Dettori, G.; Idini, M. V.; Pisano, L.; Sechi, G. Tetrahedron 2003, 59, 7961–
7966. (i) G.-Nava, M.; Jaeggy, M.; Nierengarten, H.; Masson, P.; Guillon, D.;
Van Dorsselaer, A.; Nierengarten, J.-F. Tetrahedron Lett. 2003, 44, 3039–3042.
(j) Årstad, E.; Hoff, P.; Skattebøl, L.; Skretting, A.; Breistøl, K. J. Med. Chem.
2003, 46, 3021–3032. (k) Fabbrini, G.; Menna, E.; Maggini, M.; Canazza, A.;
Marcolongo, G.; Meneghetti, M. J. Am. Chem. Soc. 2004, 126, 6238–6239. (l)
Labrue, F.; Pons, B.; Ricard, L.; Marinetti, A. J. Organomet. Chem. 2005, 690,
2285–2290. (m) Nielsen, C. B.; Johnsen, M.; Arnbjerg, J.; Pittelkow, M.; McIlroy,
S. P.; Ogilby, P. R.; Jorgensen, M. J. Org. Chem. 2005, 70, 7065–7079.
(11) See for example: (a) Yokomatsu, T.; Murano, T.; Suemune, K.; Shibuya,
S. Tetrahedron 1997, 53, 815–822. (b) Li, Z.; Yeo, S. L.; Pallen, C. J.; Ganesan,
A. Bioorg. Med. Chem. Lett. 1998, 8, 2443–2446. (c) Park, S. B.; Standaert,
R. F. Tetrahedron Lett. 1999, 40, 6557–6560. (d) Cockerill, G. S.; Easterfield,
H. J.; Percy, J. M.; Pintat, S. J. Chem. Soc., Perkin Trans. 1 2000, 2591–2599.
(e) Bhattacharya, A. K.; Stolz, F.; Schmidt, R. R. Tetrahedron Lett. 2001, 42,
5393–5395. (f) Beeton, C.; Pennington, M. W.; Wulff, H.; Singh, S.; Nugent,
D.; Crossley, G.; Khaytin, I.; Calabresi, P. A.; Chen, C.-Y.; Gutman, G. A.;
Chandy, K. G. Mol. Pharmacol. 2005, 67, 1369–1381. (g) Combs, A. P.; Yue,
E. W.; Bower, M.; Ala, P. J.; Wayland, B.; Douty, B.; Takvorian, A.; Polam,
P.; Wasserman, Z.; Zhu, W.; Crawley, M. L.; Pruitt, J.; Sparks, R.; Glass, B.;
Modi, D.; McLaughlin, E.; Bostrom, L.; Li, M.; Galya, L.; Blom, K.; Hillman,
M.; Gonneville, L.; Reid, B. G.; Wei, M.; Becker-Pasha, M.; Klabe, R.; Huber,
R.; Li, Y.; Hollis, G.; Burn, T. C.; Wynn, R.; Liu, P.; Metcalf, B. J. Med. Chem.
2005, 48, 6544–6548.
The Rh-dppf catalyzed cross-coupling of 1a with diethyl
3-iodopropylphosphonate (5) or diethyl 4-iodobutylphosphonate
(6) took place far less selectively, producing the desired cross-
coupling product 7 or 8 in reduced yields, i.e., 31% or 18%,
respectively (Scheme 1). Together with the fact that in the Rh-
dppf catalyzed reaction between 1a and iodoethane (9) the yield
(13) In comparison with the vast numbers of studies on Pd or Ni catalysis in
the cross-coupling of carbon electrophiles, R-X, with organometallic compounds,
R′-m, those on Rh remain few: (a) Larock, R. C.; Hershberger, S. S. J.
Organomet. Chem. 1982, 225, 31–41. (b) Larock, R. C.; Narayanan, K.;
Hershberger, S. S. J. Org. Chem. 1983, 48, 4377–4380. (c) Evans, P. A.;
Uraguchi, D. J. Am. Chem. Soc. 2003, 125, 7158–7159. (d) Evans, P. A.; Leahy,
D. K. J. Am. Chem. Soc. 2003, 125, 8974–8975. (e) Uemura, K.; Satoh, T.;
Miura, M. Org. Lett. 2005, 7, 2229–2231. (f) Yasui, H.; Mizutani, K.; Yorimitsu,
H.; Oshima, K. Tetrahedron 2006, 62, 1410–1415. (g) Wu, J.; Zhang, L.; Luo,
Y. Tetrahedron Lett. 2006, 47, 6747–6750. (h) Wu, J.; Zhang, L.; Gao, K. Eur.
J. Org. Chem. 2006, 5260–5263. (i) Kantam, M. L.; Roy, S.; Roy, M.; Sreedhar,
B.; Choudary, B. M.; De, R. L. J. Mol. Catal. A: Chem. 2007, 273, 26–31. (j)
Zhang, L.; Wu, J. AdV. Synth. Catal. 2008, 350, 2409–2413.
(14) There exists no precedent for the catalytic alkyl-aryl cross-coupling with
alkyl electrophiles leading to phosphoryl-substituted alkylarenes, except for two
examples using R-phosphoryl-substituted alkyl halides as an actiVated alkyl
electrophile. Strotman, N. A.; Sommer, S.; Fu, G. C. Angew. Chem., Int. Ed
2007, 47, 3556–3558.
(12) See for example: (a) Grawe, T.; Schrader, T.; Zadmard, R.; Kraft, A. J.
Org. Chem. 2002, 67, 3755–3763. (b) Freisinger, E.; Griesser, R.; Lippert, B.;
Moreno-Luque, C. F.; Niclos-Gutierrez, J.; Ochocki, J.; Operschall, B. P.; Sigel,
H. Chem. Eur. J. 2008, 14, 10036–10046.
J. Org. Chem. Vol. 74, No. 7, 2009 2795

Takahashi et al.
TABLE 2. Synthesis of Diethyl 2-Arylethylphosphonatea
FIGURE 2. Effect of the phosphoryl group.
afforded the cross-coupling product 14a in 80% yield based on
the presumed intermediate 15. Thus, alkyl-aryl cross-coupling
with the alkyl electrophile 11 was achieved on the basis of the
utility of the aryl electrophile 13a via the polarity inversion of
the alkyl electrophile 11 with 2 equiv of the arylzinc compounds
1a.
More conveniently, the zinc compound 15, a phosphoryl
analogue of the Reformatsky reagent, was prepared by the
reaction between 11 and zinc powder in THF16,17 and was
utilized in the reaction with 13a in the presence of Rh-dppf,
producing the desired product 14a in 72% isolated yield as
shown in Table 3 (entry 1). Various functional groups such as
OCH3 (entry 2), CH2OSi(CH3)2C(CH3)3 (entry 3), N(CH3)2
(entry 4), Cl (entry 5), CO2C2H5 (entry 6), or CN (entry 7) on
the aryl electrophiles 13b-g did not interfere with the Rh-dppf
catalyzed reaction with 15 to afford the corresponding coupling
products 14b-g in good yields (entries 2-7). Meanwhile,
among the substituent groups at the ortho position, some like
CO2CH3 (entry 10) or COPh (entry 11) were tolerated in the
reaction,18 but some like OCH3 (entry 8) or CN (entry 9)
inhibited the reaction, analogous to the ones in 1g,h (vide supra).
In conclusion, a novel, facile, and efficient synthetic method
for R- or ꢀ-phosphoryl-substituted alkylarenes has been devel-
oped using the Rh-dppf catalyzed Negishi alkyl-aryl cross-
coupling, featuring inhibition of the ꢀ-hydride elimination by
the phosphoryl group at the ꢀ-carbons of the nonactivated alkyl
electrophile or the utility of the phosphoryl analogue of the
Reformatsky reagent as the alkyl nucleophile, which not only
provides an alternative to precedents including the Arbuzov
reaction under mild conditions but also assures the unique and
specific catalysis by Rh in alkyl-aryl cross-coupling.
a Molar ratio: ArZnI/2/[RhCl(cood)]2/dppf ) 1.4:1:0.05:0.1. b Yields
in parentheses were determined by GLC.
SCHEME 1. Reaction of 1a with 2, 5, 6, or 9
of the cross-coupling product 10 was not increased by the
addition of diethyl 2-phenylethylphosphonate (3a) in the reaction
solutions (Scheme 1), these observations suggest the essential
role exerted by the phosphoryl group, which exists in the
reaction components and near the Rh center, to promote the
cross-coupling with alkyl electrophiles possessing ꢀ-hydrogens
(Figure 2).
Experimental Section
Preparation of Diethyl (Iodozincio)methylphosphonate (15)
in THF. In a reaction flask, Zn powder (1.31 g, 20 mmol) was
heated by a heat-gun for 10 min under vacuum (1 Torr). To the
solid were added diethyl 1-iodomethylphosphonate (11) (2.78 g,
10 mmol) and THF (5 mL), and the resulting mixture was stirred
A nearer phosphoryl group, for example, the one in diethyl
1-iodomethylphosphonate (11), however, did not assist the cross-
coupling in its reaction with arylzinc compounds 1a,b,e. Instead,
the homocoupling products of the arylzinc compounds 12a,b,e
were obtained in quantitative yields (Scheme 2).15 Fortunately,
the addition of iodobenzene (13a) to the resulting solution,
followed by heating of the obtained solution at 60 °C for 10 h,
(16) To the best of our knowledge, there exists no precedent for the
preparation of 15, although the fluorine derivative of 15, (EtO)2P(O)CF2ZnI,
has been known for a long time and is widely utilized as a synthetic
intermediate.11a,b (a) Qui, W.; Burton, D. J. Tetrahedron Lett. 1996, 37, 77–81.
(b) Yokomatsu, T.; Abe, H.; Yamagishi, T.; Suemune, K.; Shibuya, S. J. Org.
Chem. 1999, 64, 8413–8418.
(17) [(MeO)2P(O)CH2]2Zn was recently prepared by the deprotonation of
(MeO)2P(O)CH3 with Zn(tmp)2 (tmp ) 2,2,6,6-tetramethylpiperidinyl anion),
which was applied to the Pd-catalyzed cross-coupling with bromobenzene leading
to PhCH2P(O)(OMe)2. We noticed that this is the only report that describes the
catalytic synthesis of phosphoryl-substituted alkylarenes using non-fluoroalkyl
nucleophiles as the coupling component: Hlavinka, M. L.; Hagadorn, J. R.
Organometallics 2007, 26, 4105–4108.
(15) A similar reaction, the oxidative homo-coupling of arylmetallic com-
pounds with activated alkyl electrophiles, was reported, in which arylboronic
acids afford biaryls by catalysis with palladium using R-bromoacetate as the
oxidant:(a) Goossen, L. K. Chem. Commun. 2001, 669–670. (b) Lei, A.; Zhang,
X. Tetrahedron Lett. 2002, 43, 2525–2528.
(18) The beneficial effect of carbonyl groups at the ortho-position of arylzinc
compounds is observed in the Rh-catalyzed cross-coupling with non-activated
alkyl electrophiles.9a
2796 J. Org. Chem. Vol. 74, No. 7, 2009

R- or ꢀ-Phosphoryl-Substituted Alkylarenes
SCHEME 2. Synthesis of 14a from 11
TABLE 3. Synthesis of Diethyl Arylmethylphosphonatea
Hz, 9H), 1.08 (d, J ) 17.7 Hz, 2H), 1.28 (t, J ) 7.1 Hz, 6H),
3.98-4.06 (m, 4H); 13C NMR (75.5 MHz, CDCl3) δ -8.3 (d, J )
2.3 Hz), 5.9 (d, J ) 134.6 Hz), 16.4 (d, J ) 6.6 Hz), 61.0 (d, J )
6.3 Hz); 31P NMR (121 MHz, CDCl3) δ 37.6.
Preparation of Diethyl 2-[4-(Ethoxycarbonyl)phenyl]ethylphos-
phonate (3e). Representative Procedure. To the mixture prepared
by the reaction of [RhCl(cod)]2 (10 mg, 0.02 mmol), dppf (22.2
mg, 0.04 mmol), and THF (0.05 mL) at ambient temperature for
10 min was added 0.47 mL of a 1.2 mol/L THF solution of 1e
(0.56 mmol), and the mixture was stirred for 5 min at the same
temperature. To the resulting solution was added diethyl 2-iodo-
ethylphosphonate (2) (0.075 mL, 0.4 mmol), and the mixture was
stirred at 40 °C for 1 h. After the successive treatment of the
resulting mixture with hydrazine monohydrate and brine, the ether
extract was chromatographed on a silica gel column, affording 77
1
mg of 3e (61%): oil; IR (neat) 1279, 1718 cm-1; H NMR (300
MHz, CDCl3) δ 1.29 (dt, J ) 7.1, 1.8 Hz, 6H), 1.36 (dt, J ) 7.2,
1.8 Hz, 3H), 1.98-2.10 (m, 2H), 2.90-2.99 (m, 2H), 4.08 (quintet,
J ) 6.9 Hz, 4H), 4.34 (q, J ) 7.1 Hz, 2H), 7.24 (d, J ) 8.1 Hz,
2H), 7.95 (d, J ) 8.4 Hz, 2H); 13C NMR (75.5 MHz, CDCl3) δ
14.2, 16.3 (d, J ) 6.0 Hz), 27.1 (d, J ) 140.5 Hz), 28.6 (d, J ) 4.5
Hz), 60.8, 61.6 (d, J ) 6.6 Hz), 128.0, 128.6, 129.8, 146.1 (d, J )
17.1 Hz), 166.4; 31P NMR (121 MHz, CDCl3) δ 30.9; HRFAB-
MS calcd for C15H24O5P, 315.1361, found (M + H)+ 315.1364.
Preparation of Diethyl (2-Benzoylphenyl)methylphosphonate
(14k). Representative Procedure. To the mixture prepared by the
reaction of [RhCl(cod)]2 (10 mg, 0.02 mmol) and dppf (22.2 mg,
0.04 mmol) was added 0.47 mL of a 1.2 mol/L THF solution of 15
(0.56 mmol), and the mixture was stirred for 5 min at the same
temperature. To the resulting solution was added (2-iodophe-
nyl)phenylmethanone (13k) (123 mg, 0.4 mmol), and the mixture
was stirred at 60 °C for 10 h. After the successive treatment of the
resulting mixture with hydrazine monohydrate and brine, the ether
extract was chromatographed on a silica gel column, affording 113
1
mg of 14k (85%): oil; IR (neat) 1269, 1662 cm-1; H NMR (300
MHz, CDCl3) δ 1.08 (t, J ) 7.2 Hz, 6H), 3.52 (d, J ) 22.5 Hz,
2H), 3.83-3.95 (m, 4H), 7.28-7.32 (m, 2H), 7.41-7.48 (m, 4H),
7.54-7.56 (m, 1H), 7.79-7.83 (m, 2H); 13C NMR (75.5 MHz,
CDCl3) δ 16.1 (d, J ) 6.0 Hz), 29.9 (d, J ) 136.6 Hz), 61.9 (d, J
) 6.7 Hz), 126.0 (d, J ) 3.7 Hz), 128.2, 129.9 (d, J ) 3.0 Hz),
130.4, 130.6 (d, J ) 3.2 Hz), 131.6 (d, J ) 10.0 Hz), 132.0 (d, J
) 5.7 Hz), 133.0, 137.7, 138.2 (d, J ) 6.6 Hz), 197.7; 31P NMR
(121 MHz, CDCl3) δ 26.6; HRFAB-MS calcd for C18H22O4P,
333.1256, found (M + H)+ 333.1258.
a Molar ratio: ArI/15/[RhCl(cood)]2/dppf ) 1.4:1:0.05:0.1.
Supporting Information Available: General methods, com-
pound characterization data, and copies of the 1H and 13C NMR
spectra. This material is available free of charge via the Internet
at http://pubs.acs.org.
at ambient temperature for 24 h. Then, 0.30 mL of the supernatant
solution was transferred to other flask containing chlorotrimethyltin
(0.12 g, 0.60 mmol), and the mixture was stirred at the same
temperature for 3 h. After the successive treatment of the resulting
solution with aqueous KF and brine, the ether extract afforded 110
mg of diethyl (trimethylstannyl)methylphosphonate (16),19 exhibit-
ing the concentration of 15 to be 1.2 mol/L. 16: oil; IR (neat) 1030,
1056, 1243 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.23 (t, J ) 27.3
JO900142B
(19) Weichmann, H.; Ochsler, B.; Duchek, I.; Tzschach, A. J. Organomet.
Chem. 1979, 182, 465–476.
J. Org. Chem. Vol. 74, No. 7, 2009 2797