Palladium-catalyzed direct (hetero)arylation of ethyl oxazole-4- carboxylate: An efficient access to (hetero)aryloxazoles

Article abstract of DOI:10.1021/jo801093n

(Chemical Equation Presented) A straightforward route toward 2-(hetero)arylated and 2,5-di(hetero)arylated oxazoles through regiocontrolled palladium-catalyzed direct (hetero)arylation of ethyl oxazole-4-carboxylate with iodo-, bromo-, and chloro(hetero)a

Full text of DOI:10.1021/jo801093n

As pioneering work, Ohta reported the regioselective C-5 direct
heteroarylation of oxazole with 2-chloropyrazine under standard
conditions [Pd(PPh3)4/KOAc/DMF].2e The process was further
used to introduce the oxazole nucleus at its position 5 on
heterocyclic pharmaceutics.1a More recently, novel efficient
catalyst systems for C-2 arylation of azoles including the
challenging oxazole were actively developed. Thus, Bellina and
Daugulis reported the first two examples of regioselective direct
C-2 phenylation of oxazole with phenyl iodide or 4-methoxy-
phenyl iodide under base-free conditions2b [CuI (2 equiv), 5
mol % Pd(OAc)2] or palladium-free conditions2c [5 mol % CuI,
tBuOLi (2 equiv)] providing 2-aryloxazoles in 63% or 23%
yields, respectively. Doucet2d and Bhanage2e designed two novel
palladium-bidentate ligand catalysts [PdCl(C3H5)(dppb) and
Pd(TMHD)2] that proved to be effective in C-2 regioselective
arylation of oxazole with 4-tert-butylbromobenzene, iodoben-
zene, or 4-methoxyiodobenzene in 69%, 62%, or 63% yields,
respectively. To date regioselective direct arylation of oxazole
remains sparse compared to the broad range of heterocyclic
targets, and there is a need to develop versatile routes to
(hetero)aryloxazoles via regioselective direct arylation of oxa-
zoles with halo(hetero)arenes. For this purpose, we recently
turned to the commercially available ethyl oxazole-4-carboxylate
1 and we reported the preferential C-2 versus C-5 palladium-
catalyzed direct C-H phenylation of 1 with phenyl iodide under
standard conditions.4 In this note, we report new developments
of this method on the regiocontrolled C-2 (hetero)arylation of
1 followed by a C-5 (hetero)arylation with various (hetero)aryl
halides. This method allows simple and fast access to 2-(het-
ero)aryl- and 2,5-di(hetero)aryloxazole-4-carboxylates, which
are common features of various oxazole-containing natural
products such as the thiopeptide antibiotic GE37468A.5 The
removal of the ethyl carboxylate function used as a temporary
blocking group was examined to prepare the 2-mono(het-
ero)aryl- and 2,5-di(hetero)aryloxazoles via a direct coupling
strategy, which can be directly run to a innovative synthetic
approach toward 2,5-di(hetero)aryloxazole natural products and
scintillators.6
Palladium-Catalyzed Direct (Hetero)arylation of
Ethyl Oxazole-4-carboxylate: An Efficient Access
to (Hetero)aryloxazoles
Ce´cile Verrier, Thibaut Martin, Christophe Hoarau,* and
Francis Marsais
Institut de Chimie Organique Fine (IRCOF) associe´ au
CNRS (UMR 6014), INSA et UniVersite´ de Rouen, BP08
76131 Mont Saint Aignan, France
christophe.hoarau@insa-rouen.fr
ReceiVed May 21, 2008
A straightforward route toward 2-(hetero)arylated and 2,5-
di(hetero)arylated oxazoles through regiocontrolled pal-
ladium-catalyzed direct (hetero)arylation of ethyl oxazole-
4-carboxylate with iodo-, bromo-, and chloro(hetero)aromatics
followed by a two-step hydrolysis/decarboxylation sequence
was described. The method was applied here to a neat
synthesis of two 2,5-di(hetero)aryloxazole natural products,
balsoxin and texaline.
(Hetero)aryl-substituted oxazoles are common features of a
wide range of biologically active natural products. They are also
of considerable interest in medicinal chemistry and as organic
materials. In recent years, direct (hetero)arylation has emerged
as an attractive alternative to the commonly employed cross-
coupling reactions because it does not require the rather tricky
preliminary preparation of the requisite metallated or haloge-
nated (hetero)arene. Several reviews highlight the broad scope
of this strategy, high functional group tolerance, atom economy,
and mild reaction conditions.1 However, this straightforward
approach is penalized by the regioselectivity difficulties par-
ticularly with the unsubstituted oxazole at positions 2 and 5.2,3
In the course of the direct phenylation of 1 with phenyl iodide
using a combination of Pd(OAc)2 and Cs2CO3, we proved that
the solvent/ligand pair is of main importance to control the
selectivity of the C-2 arylation versus 5-monoarylation and 2,5-
(3) Examples of C-2 or C-5 direct (hetero)arylations of 5- or 2-monosub-
stituted oxazoles: (a) Besselie`re, F.; Mahuteau-Betzer, F.; Gierson, D. S.; Piguel,
S. J. Org. Chem. 2008, 73, 3278–3280. (b) Ohnmacht, S. A.; Mamone, P.;
Culshaw, A. J.; Greaney, M. F. Chem. Commun. 2008, 10, 1241–1243. (c)
Hodgett, K. J.; Kershaw, M. T. Org. Lett. 2003, 5, 2911–2914. (d) Pivsa-Art,
S.; Fukui, Y.; Miura, M.; Nomura, M. Bull. Chem. Soc. Jpn. 1998, 71, 467–
473. (e) Pivsa-Art, S.; Fukui, Y.; Miura, M.; Nomura, M. Bull. Chem. Soc. Jpn.
1998, 71, 467–473.
(4) Hoarau, C.; Du Fou de Kerdaniel, A.; Bracq, N.; Grandclaudon, P.;
Couture, A.; Marsais, F. Tetrahedron Lett. 2005, 46, 8573–8577.
(5) (a) Hughes, R. A.; Moody, C. Angew. Chem., Int. Ed. 2007, 46, 7930–
7954. (b) Bagley, M. C.; Dale, J. W.; Meritt, E. A.; Xiong, X. Chem. ReV. 2005,
105, 685–714. (c) Yeh, V. S. C. Tetrahedron 2004, 60, 11995–12402.
(6) (a) Charier, S.; Ruel, O.; Baudin, J.-B.; Alcor, D.; Allemand, J.-F.; Meglio,
A.; Jullien, L.; Valeur, B. Chem. Eur. J. 2006, 12, 1097–1113. (b) Clapham, C.;
Sutherland, A. J. Chem. Commun. 2003, 84–85. (c) McCrain, M. C.; Hine, A. V.;
Sutherland, A. J. J. Mater. Chem. 2003, 13, 225–231. (d) Clapham, C.;
Sutherland, A. J. Tetrahedron Lett. 2000, 41, 2253–2256. (e) Diwu, Z.; Zhang,
C.; Klaubert, D. H.; Haugland, R. P. J. Photochem. Photobiol. A: Chem. 2000,
131, 95–100.
(1) (a) Alberico, D.; Scott, M. E.; Lautens, M. Chem. ReV. 2007, 107, 174–
238. (b) Campeau, L.-C.; Stuart, D. R.; Fagnou, K. Aldrichimica Acta 2007, 40,
35–41. (c) Stuart, D. R.; Fagnou, K. Science 2007, 316, 1172–1175. (d) Kakiuchi,
F.; Chatani, N. AdV. Synth. Catal. 2003, 354, 1077–1101. (e) Lablinger, J. A.;
Bercaw, J. E. Nature 2002, 417, 507–514. (f) Ritleng, V.; Sirlin, C.; Pfeffer, M.
Chem. ReV. 2002, 102, 1731–1770. (g) Miura, M.; Nomura, M. Top. Curr. Chem.
2002, 219, 211–241. (h) Fujiwara, Y.; Chengguo, J. Pure Appl. Chem. 2001,
73, 319–324. (i) Dyker, G. Angew. Chem., Int. Ed. 1999, 38, 1698–1712. (j)
Shilov, A.; Shul’pin, G. Chem. ReV. 1997, 97, 2879–2932.
(2) Examples of C-2 or C-5 regioselective direct (hetero)arylations of oxazole:
(a) Derridj, F.; Djebbar, S.; Benali-Baitich, O.; Doucet, H. J. Organomet. Chem.
2008, 693, 135–144. (b) Nandurkar, N. S.; Bhanushali, M. Y.; Bhor, M. D.;
Bhanage, B. M. Tetrahedron Lett. 2008, 49, 1045–1048. (c) Daugulis, O.; Do,
H.-Q. J. Am. Chem. Soc. 2007, 129, 12404–12405. (d) Bellina, F.; Cauteruccio,
S.; Rossi, R. Eur. J. Org. Chem. 2006, 1379–1382. (e) Ohta, A.; Akita, Y.;
Ohkuwa, T.; Chiba, M.; Fukunaga, R.; Miyafuyi, A.; Nakata, T.; Tani, N.;
Aoyagi, Y. Heterocycles 1990, 31, 1951–1958.
10.1021/jo801093n CCC: $40.75
Published on Web 08/15/2008
2008 American Chemical Society
J. Org. Chem. 2008, 73, 7383–7386 7383

TABLE 1. Direct C-2 and C-5 Phenylation of Ethyl
Oxazole-4-carboxylate (1) with Iodo- and Chlorobenzenesa
TABLE 2. Direct C-2 (Hetero)arylation of Ethyl Oxazole-4-
carboxylate (1) with Iodo-, Bromo-, and Chloro(hetero)aromaticsa
a Reaction conditions: [1]/[PhX]/[Pd(OAc)2]/[ligand]/[Cs2CO3]
)
0.35:0.35:0.017:0.035:0.7 (in mmol), in dioxane or toluene (1 mL) under N2
atmosphere at 110 °C for 18 h; n.r. ) no reaction. b Yield of isolated
product over two runs. c Buchwald’s JohnPhos ligand: 2-(dicyclohexyl-
phosphino)biphenyl. d IMes: 1,3-bis-(mesitylimidazolyl)carbene. e 16% of
3a and 10% of ethyl 5-phenyloxazole-4-carboxylate. f 15% of 3a. g 11% of
3a. h 0.7 mmol of PhCl.
diarylation of oxazole-4-carboxylates. Bulky ligands greatly
favor the formation of ethyl 2-phenyloxazole-4-carboxylate
(Table 1, entries 1-3), 86% using P(o-tol)3 in toluene, 69%
with Buchwald’s JohnPhos ligand in dioxane, or 88% with IMes
in dioxane. Therefore, the subsequent C-5 phenylation of 2a to
the ethyl 2,5-diphenyloxazole-4-carboxylate 3a could be achieved
with P(o-tol)3 either in dioxane (81%) or toluene (96%). With
the aim to extend the method to a broad range of (hetero)arene
halides, we first checked the direct coupling of phenyl chloride
with 1 (Table 1, entries 4-6). We found that Buchwald’s
JohnPhos ligand in dioxane carried out the two-step C-2 and
then C-5 phenylation of 1 to 2a then 3a in 79% and 52% yields
(entry 5). The use of P(o-tol)3 in toluene allowed exclusively
the C-2 phenylation of 1 in 71% yield when using a 2-fold
excess of phenyl chloride (entry 4). Interestingly, the 2,5-
diphenylated compound 3a was not observed due to the poor
efficiency of P(o-tol)3 in toluene in subsequent C-5 phenylation
of 2a to 3a (16%). As consequence of probing C-2 (hetero)ary-
lation of 1 with a number of halo(hetero)arenes, we chose the
ligand/solvent pairs that were much more effective in C-2 than
in C-5 phenylation of 1 to avoid the side production of the
undesired 2,5-diarylated compound. Thus from the results
depicted in Table 1 (entries 1-6), two efficient ligand/solvent
pairs were retained depending on the (hetero)aryl halide used.
The (hetero)arylation of 1 with (hetero)aryl iodides and bromides
was carried out with Buchwald’s JohnPhos ligand in dioxane,
whereas P(o-tol)3 in toluene for direct coupling of 1 with
(hetero)aryl chlorides was used. The results depicted in Table
2 showed that the selective C-2 (hetero)arylation of 1 could be
successfully accomplished with a large number of iodo- and
bromo(hetero)arenes leading to the corresponding 2-(hetero)aryl-
oxazole-4-carboxylates 2b-j in 59% to 90% yields range. Most
remarkably, almost all (hetero)aryl chlorides proved to be better
coupling partners than iodo- and bromo(hetero)arenes for direct
coupling since 2-(hetero)aryloxazole-4-carboxylates 2b-j were
obtained in higher yields (66-98%). As expected, both 5-(het-
ero)arylated and 2,5-diarylated products were not formed with
1 equiv of (hetero)aryl halides. Nevertheless, an excess of
(hetero)aryl halides could be useful sometimes along with
a Reaction conditions: [1]/[Ar2X]/[Pd(OAc)2]/[ligand]/[Cs2CO3]
)
0.35:0.35:0.017:0.035:0.7 (in mmol), in dioxane or toluene (1 mL) under
N2 atmosphere at 110 °C for 18 h; n.r. ) no reaction. b Yield of isolated
product over two runs. c Buchwald’s JohnPhos ligand: 2-(dicyclohexyl-
e
phosphino)biphenyl. d 0.7 mmol of halogeno(hetero)aromatic. [1]/[Ar2X]/
[Pd(OAc)2]/[ligand]/[Cs2CO3] ) 0.35:0.7:0.035:0.07:0.7 (in mmol). f 36%
of 2,5 diarylated oxazole. g 22% of 2,5 diarylated oxazole.
increasing amounts of catalyst (10 mol %) and ligand (20 mol
%) to optimize the yield of C-2 (hetero)aryloxazoles versus the
side-production of bis-arenes arising from the (hetero)aryl
halides homocoupling (entries 1, 3, 5, 6, 9, 13, and 18). It should
also be noted that the direct (hetero)arylation of 1 is fully
compatible with such reactive functions as cyano and formyl
(entries 1-4) as well as the electron-rich amino group of
4-aminoiodobenzene (entry 7). Surprisingly, P(o-tol)3 in toluene
proved to be an effective ligand in the direct coupling of 1 with
the deactivated 4-methoxychlorobenzene (entry 6), whereas the
same reaction with 4-aminochlorobenzene remained unsuccess-
ful whatever catalyst was used (entry 8).
The second C-5 (hetero)arylation step of 2-(hetero)aryl-
oxazole-4-carboxylates with various (hetero)aryl halides was
then studied. Preliminary results of the C-5 direct phenylation
of 2a with phenyl iodide (Table 1) showed that P(o-tol)3 in
toluene can be used with (hetero)aryl iodides (entry 1), whereas
Buchwald’s JohnPhos ligand in dioxane or toluene is better in
the case of (hetero)aryl chlorides (entry 5). Under these
conditions, the second C-5 coupling step of 2a with various
(hetero)aryl halides led to the expected 5-(hetero)aryl-2-phe-
nyloxazole-4-carboxylates 3b-f in fair to good yields (Table
3). Iodo- and bromo(hetero)arenes proved to be very reactive
and allowed good to excellent yields (72-95%) of oxazole-4-
carboxylates 3b-f. As with chlorobenzene, 2 equiv of 2-chlo-
ropyridine and 2-chlorothiophene were required to produce 3d
7384 J. Org. Chem. Vol. 73, No. 18, 2008

TABLE 3. Direct C-5 (Hetero)arylation of 2-Phenyloxazole-
4-carboxylate (2a) with Iodo-, Bromo-, and
Chloro(hetero)aromaticsa
TABLE 4. 2,5-Di(hetero)arylated Oxazole-4-carboxylates
Synthesisa
a Reaction conditions: [2]/[Ar5X]/[Pd(OAc)2]/[ligand]/[Cs2CO3]
)
0.35:0.35:0.017:0.035:0.7 (in mmol), in dioxane or toluene (1 mL) under
N2 atmosphere at 110 °C for 18 h; n.r. ) no reaction. b Yield of isolated
a Reaction conditions: [2a]/[Ar5X]/[Pd(OAc)2]/[ligand]/[Cs2CO3]
)
c
product over two runs. [2]/[Ar5X]/[Pd(OAc)2]/[ligand]/[Cs2CO3]
)
0.35:0.35:0.017:0.035:0.7 (in mmol), in dioxane or toluene (1 mL) under
N2 atmosphere at 110 °C for 18 h; n.r. ) no reaction. b Yield of isolated
product over two runs. c Buchwald’s JohnPhos ligand: 2-(dicyclohexyl-
0.35:0.7:0.035:0.07:0.7 (in mmol).
d [2a]/[Ar5X]/[Pd(OAc)2]/[ligand]/[Cs2CO3]
)
TABLE 5. 2-(Hetero)arylated- and 2,5-Di(hetero)arylated Oxazoles
Synthesis
phosphino)biphenyl.
0.35:0.7:0.035:0.07:0.7 (in mmol). e Toluene as solvent.
and 3f in good 72% yields. The same procedure with P(o-tol)3
in toluene was further successfully used to prepare 2,5-
di(hetero)aryloxazole-4-carboxylates 4-8 in good to excellent
yields (81-100%) (Table 4).
With a selective C-2 and subsequent C-5 (hetero)arylation
process of ethyl oxazole-4-carboxylate 1 in hand, we turned
our attention to the preparation of 2-mono(hetero)aryl- and 2,5-
di(hetero)aryloxazoles by removal of the ester group through a
two-step LiOH-hydrolysis followed by a CuO-induced decar-
boxylation sequence. This protocol turned out to be very
effective especially with sensitive functions such as formyl and
cyanide groups and provided the expected (hetero)aryloxazoles
9-14 in good (75%) to quantitative yields (Table 5). Some of
these 2,5-di(hetero)aryloxazoles are natural products, such as
balsoxin 11 and texaline 13 isolated from Amyris species of
plants in the Caribbean.7
In conclusion, we have developed a general palladium-
catalyzed C-2 and subsequent C-5 direct (hetero)arylation
process of ethyl oxazole-4-carboxylate 1. It appeared to be very
efficient and general with regard to both halogens (I, Br, Cl)
and coupling partners, giving a clean access to a great variety
of ethyl 2-(hetero)aryloxazole-4-carboxylates and ethyl 2,5-
di(hetero)aryloxazole-4-carboxylates. The carboxylic ester func-
tion at C-4 could be then easily removed to readily afford the
corresponding 2-(hetero)aryloxazoles and 2,5-di(hetero)aryl-
oxazoles. This first versatile approach toward 2-(hetero)aryl-
oxazoles and 2,5-di(hetero)aryloxazoles based upon a direct C-H
a Yield of isolated product.
arylation strategy was successfully applied to the synthesis of
natural 2,5-di(hetero)aryloxazoles. Thus balsoxin and texaline
were cleanly prepared in three steps in 54% and 61% overall
(7) (a) Dom´ınguez, X. A.; de la Fuenta, G.; Gonza´lez, A. G.; Reina, M.;
Timo´n, I. Heterocycles 1988, 27, 35–38. (b) Burke, B.; Parkins, H.; Talbot, A. M.
Heterocycles 1979, 12, 349–351.
J. Org. Chem. Vol. 73, No. 18, 2008 7385

Celite and concentration under vacuo, the crude product was purified
by flash column chromatography on silica gel using a mixture of
ethyl acetate/petrolum ether as the eluent to get 2,5-diarylated
oxazolecarboxylates 3b-f and 4-8.
yields, respectively, from 1 using optimized experimental
conditions.8,9
Experimental Section
Ethyl 2-phenyl-5-(2-nitrophenyl)oxazole-4-carboxylate (3b): white
1
General Procedure for C-2 Direct Coupling of Oxazole-
4-carboxylate 1 with (Hetero)aryl Iodides and Bromides
(Chlorides). To a 10-mL sealed tube were added oxazolecarboxy-
late 1 (0.35 mmol), (hetero)aryl bromide or iodide (chloride) (0.35
mmol), Pd(OAc)2 (4 mg, 0.017 mmol,), Cs2CO3 (231 mg, 0.70
mmol), JohnPhos (P(o-tol)3) (12 mg (11 mg)), 0.035 mmol), and
dioxane (toluene) (1 mL). The resulting mixuture was stirred under
N2 at 110 °C. After filtration through Celite and concentration under
vacuo, the crude product was purified by flash column chromatog-
raphy on silica gel using a mixture of ethyl acetate/petrolum ether
as the eluent to get 2-arylated oxazolecarboxylates 2b-j.
Ethyl 2-(4-cyanophenyl)oxazole-4-carboxylate (2b): white solid
(65% (85%)), mp ) 123-124 °C. 1H NMR (CDCl3, 300 MHz) δ
1.40 (t, 3H, J ) 7.1 Hz), 4.43 (q, 2H, J ) 7.1 Hz), 7.77 (d, 2H, J
) 8.7 Hz), 8.22 (d, 2H, J ) 8.7 Hz), 8.32 (s, 1H); 13C NMR (CDCl3,
75 MHz) δ 14.3, 62.3, 114.0, 115.0, 118.0, 127.5, 129.0, 130.6,
132.3, 132.8, 144.6, 153.6, 161.6; IR (KBr) υ 1551, 1572, 1654,
1717, 2230, 3100 cm-1. Anal. Calcd for C13H10N2O3 (242.2): C,
64.46; H, 4.16; N, 11.56. Found: C, 64.63; H, 4.10; N, 11.54.
The characterization data of compounds 2c-j and others detailed
C-2 direct arylating procedures are available in Supporting Informa-
tion.
solid (84%), mp ) 136-137 °C. H NMR (CDCl3, 300 MHz) δ
1.27 (t, 3H, J ) 7.2 Hz), 4.32 (q, 2H, J ) 7.2 Hz), 7.48-7.50 (m,
3H), 7.66-7.73 (m, 1H), 7.74-7.77 (m, 1H), 7.77-7.79 (m, 1H),
8.11-8.13 (m, 2H), 8.18 (d, 1H, J ) 7.9 Hz); 13C NMR (CDCl3,
75 MHz) δ 14.1, 61.7, 122.8, 124.9, 126.2, 127.1, 127.5, 129.0,
130.2, 131.3, 131.5, 132.7, 132.9, 148.6, 151.0, 161.5; IR (KBr) υ
1525, 1576, 1602, 1718, 1743, 2992, 3077 cm-1. Anal. Calcd for
C18H14N2O5 (338.3): C, 63.90; H, 4.17; N, 8.28. Found: C, 63.94;
H, 4.03; N, 8.45.
Ethyl 2-(4-cyanophenyl)-5-(4-methoxyphenyl)oxazole-4-carbox-
ylate (4): white solid (97%), mp ) 192-193 °C. 1H NMR (CDCl3,
300 MHz) δ 1.41 (t, 3H, J ) 6.9 Hz), 3.87 (s, 3H), 4.43 (q, 2H, J
) 6.9 Hz), 8.64 (d, 2H, J ) 8.6 Hz), 7.76 (d, 2H, J ) 8.1 Hz),
8.10 (d, 2H, J ) 8.6 Hz), 8.23 (d, 2H, J ) 8.1 Hz); 13C NMR
(CDCl3, 75 MHz) δ 14.4, 55.5, 61.6, 114.0, 114.1, 118.3, 119.1,
127.1, 127.6, 130.3, 130.4, 132.7, 156.4, 157.1, 161.5, 162.1; IR
(KBr) υ 1507, 1578, 1610, 1709, 2227, 2837, 2947, 2994 cm-1
.
Anal. Calcd for C20H16N2O4 (348.4): C, 68.96; H, 4.63; N, 8.04.
Found: C, 69.06; H, 4.85; N, 8.21.
The characterization data of compounds 3c-f and 5-8 and other
C-5 direct arylating procedures are available in Supporting Informa-
tion.
General Procedure for C-5 Direct Coupling of 2-Aryl
Oxazole-4-Carboxylate 2a (2b,f,g,j) with (Hetero)aryl Iodides
and Bromides. To a 10-mL sealed tube were added oxazolecar-
boxylate 2a (76 mg, 0.35 mmol), (hetero)aryl bromide (0.35 mmol),
Pd(OAc)2 (4 mg, 0.017 mmol,), Cs2CO3 (231 mg, 0.70 mmol), and
P(o-tol)3 (11 mg, 0.035 mmol) in toluene (1 mL). The resulting
mixture was stirred under N2 at 110 °C. After filtration through
Acknowledgment. This work has been supported by the
CNRS, the interregional CRUNCH network, INSA, and Uni-
versity of Rouen (I.U.T.).
Supporting Information Available: Experimental proce-
dures and spectroscopic characterization (IR, analytical analysis,
1H, 13C data) of all new (hetero)arylated oxazole-4-carboxylates.
The material is available free of charge via the Internet at
http://pubs.acs.org.
(8) For balsoxin and texaline synthesis via a combined cross-coupling or
condensation and direct arylation approach, see: (a) Hodgett, K. J.; Kershaw,
M. T. Org. Lett. 2002, 4, 2905–2907. (b) References 3a and 3b.
(9) For the unique texaline synthesis via a condensation approach, see: (a)
Gildens, A. C.; Boshoff, H. I. M.; Franzblau, S. G.; Barry, C.; Copp, B. R.
Tetrahedron Lett. 2005, 46, 7355–7357.
JO801093N
7386 J. Org. Chem. Vol. 73, No. 18, 2008