References and Notes
1a
Fretz H.
Tetrahedron Lett.
1996,
37:
8479
1b
Boussie TR.
Murphy V.
Hall KA.
Coutard C.
Dales C.
Petro M.
Carlson E.
Turner HW.
Powers TS.
Tetrahedron
1999,
55:
11699
2 An earlier report described a mixed
benzoin condensation on a solid support yielding benzils in trace
amounts (4-6%) only. However, further reaction
of the resin-bound benzils towards heterocycles was not reported.
See: Lenzhoff CC.
Wong JY.
Can. J. Chem.
1973,
51:
3756
3a
Cironi P.
Tulla-Puche J.
Barany G.
Albericio F.
Álvarez M.
Org. Lett.
2004,
6:
1405
3b
Cironi P.
Manzanares I.
Albericio F.
Álvarez M.
Org. Lett.
2003,
5:
2959
3c
Bräse S.
Köbberling J.
Griebenow N.
Organopalladium Reactions
in Combinatorial Chemistry, In Handbook
of Organopalladium Chemistry for Organic Synthesis
Vol.
2:
Negishi E.
John
Wiley and Sons;
New York:
2002.
p.3031
3d
Ljungdahl N.
Bromfield K.
Kann N.
Top.
Curr. Chem.
2007,
278:
89
3e
Nelson JC.
Young JK.
Moore JS.
J. Org. Chem.
1996,
61:
8160
3f
Erdélyi M.
Gogoll A.
J. Org. Chem.
2003,
68:
6431
4 The solid-phase oxidation of aromatic
TMS-protected acetylenes to α-ketocarboxylic acids with
OsO4 and NMO has been reported recently. See: Le Quement ST.
Nielsen TE.
Meldal M.
J. Comb. Chem.
2008,
10:
546
5
Mousset C.
Provot O.
Hamze A.
Bignon J.
Brion J.-D.
Alami M.
Tetrahedron
2008,
64:
4287
6a
Yusubov MS.
Filimonov VD.
Synthesis
1991,
131
6b
Yusubov MS.
Filimonov VD.
Vasilyeva VP.
Chi K.-W.
Synthesis
1995,
1234
7
Chi K.-W.
Yusubov MS.
Filimonov VD.
Synth. Commun.
1994,
24:
2119
8
Wolfe S.
Pilgrim WR.
Garrard TF.
Chamberlain P.
Can.
J. Chem.
1971,
49:
2941
9
Sieber P.
Tetrahedron
Lett.
1987,
28:
6147
10 Purities and product identities were
determined by LC-MS analysis using a Hewlett-Packard HP 1100 liquid
chroma-tography system coupled to a Micromass ZMD-400 spectrometer
equipped with an Intersil column (ODS-3, 50 × 2.1 mm).
The mobile phase was H2O (A) and MeCN (B), both containing
0.1% TFA. A gradient was used increasing from 10-95% B
in 9 min followed by a hold at 95% B for 1 min and then
re-equilibration for 3 min at a flow rate of 0.5 mL/min.
The column was maintained at 35 ˚C. Mass spectra were
acquired in either the positive or negative ion mode under electrospray
ionization (ESI). The compound purity was monitored based on the
UV absorbency at 210 nm. The presence of all desired compounds was
confirmed by their molecular mass.
11 Yields refer to the crude products
and were calculated on the basis of the initial loading of the resin.
12
Representative
Experimental Procedure for the Preparation of 1,2-Diketones
Wang
resin (6.00 g, 7.14 mmol, loading of 1.19 mmol/g, 1% cross-linking,
100-200 mesh) was suspended in DMF (40 mL). The suspension
was charged with 4-idodobenzoic
acid (3.19 g, 1.8 equiv,
12.85 mmol), 2,6-dichlorobenzoyl chloride (2.99 g, 2.0 equiv, 14.27
mmol), and pyridine (1.91 mL, 1.86 g, 3.3 equiv, 23.55 mmol), and
the reaction mixture was shaken at r.t. for 18 h. The resin was
filtered off and washed successively with DMF, MeOH, THF, as well
as CH2Cl2. Residual traces of solvent were
removed in vacuo overnight to provide the derivatized resin 2 with a theoretical loading capacity of
0.93 mmol/g based on 100% conversion. Under an
atmosphere of argon 4-iodobenzoic acid functionalized Wang resin 2 (3.00 g, 2.80 mmol, loading: 0.93 mmol/g)
was suspended in a solution of phenyl-acetylene (3.0 equiv, 858
mg, 8.41 mmol) in DMF-DIPEA (15 mL, v/v = 3:1).
Bis(triphenylphosphine)palladium(II) dichloride (197 mg, 0.1 equiv,
0.28 mmol) and copper(I) iodide (213 mg, 0.4 equiv, 1.12 mmol) were
added, and the reaction mixture was shaken at r.t. for 18 h. After
filtration, the resin was washed with DMF, 50% aq AcOH,
MeOH, THF, and CH2Cl2. Residual traces of
solvent were removed in vacuo overnight to provide the derivatized
resin 3a with a theoretical loading capacity
of 0.96 mmol/g based on 100% conversion. An analytical
sample of the resin was treated with TFA in CH2Cl2 (v/v = 1:1)
for 1 h at r.t. Filtration and evaporation yielded 4-(phenylethynyl)benzoic
acid.
LC-MS: 2.52 min, 99% (210 nm), m/z = 221 [M - H-]. ¹H NMR
(400 MHz, DMSO-d
6): δ = 7.44-7.49
(m, 3 H), 7.57-7.62 (m, 2 H), 7.66-7.70 (m, 2
H), 7.96-8.00 (m, 2 H) ppm; one proton not observed in
this spectrum. HRMS: m/z calcd for
C15H11O2 [M + H+]:
223.0754; found: 223.0754.
4-(Phenylethynyl)benzoic acid
Wang resin (3a, 209 mg, 0.20 mmol, loading:
0.957 mmol/g) was suspended in anhyd DMSO (2 mL) and charged
with iodine (51 mg, 1 equiv, 0.20 mmol). The reaction mixture was
heated to 155 ˚C for 1 h. The resin was then filtered
off and successively washed with DMF, 50% aq AcOH, MeOH,
THF, as well as CH2Cl2. Residual traces of
solvent were removed in vacuo overnight to provide the derivatized
resin 4a with a theoretical loading capacity
of 0.93 mmol/g based on 100% conversion. The resin
was cleaved with TFA-CH2Cl2 (2 mL,
v/v = 1:1) at r.t. for 1 h,
filtered, and washed with CH2Cl2 (1 mL). The
filtrate was evaporated to dryness providing 26 mg of 4-[oxo-(phenyl)acetyl]benzoic
acid (5a) in 52% yield.
LC-MS:
2.20 min, 95% (210 nm), m/z = 253 [M - H-]. ¹H NMR
(400 MHz, DMSO-d
6): δ = 7.63-7.67
(m, 2 H), 7.83 (t, J = 7.60
Hz, 1 H), 7.97 (d, J = 7.72
Hz, 2 H), 8.06 (d, J = 8.16
Hz, 2 H), 8.15 (d, J = 8.16
Hz, 2 H) ppm; one proton not observed in this spectrum. ¹³C
NMR (100 MHz, DMSO-d
6): δ = 129.60,
129.86, 129.97, 130.04, 132.21, 135.17, 135.81, 136.41, 166.39,
194.21, 194.25 ppm. HRMS: m/z calcd
for C15H11O4 [M + H+]:
255.0652; found: 255.0653.
13a
Debus H.
Liebigs Ann. Chem.
1858,
107:
199
13b
Radziszewski B.
Ber.
Dtsch. Chem. Ges.
1882,
15:
2706
Trimethyl orthoformate was used
instead of molecular sieve as the dehydrating reagent. See:
14a
Look GC.
Murphy MM.
Campbell DA.
Gallop MA.
Tetrahedron
Lett.
1995,
36:
2937
14b Quinoxaline synthesis
using molecular sieve: Ott S.
Faust R.
Synthesis
2005,
3135
15
Sarshar S.
Siev D.
Mjalli AMM.
Tetrahedron
Lett.
1996,
37:
835
16
Representative
Experimental Procedure for the Synthesis of Quinoxalines
4-[Oxo(phenyl)acetyl]benzoic
acid functionalized Wang resin (4a, 108
mg, 0.10 mmol, loading of 0.93 mmol/g) was suspended in
TMOF (3 mL) and charged with 2-amino-aniline (270 mg, 25 equiv,
2.50 mmol). The reaction mixture was shaken at r.t. for 18 h. The
resin was filtered off and washed successively with DMF, THF, as
well as CH2Cl2. The resin was cleaved with
TFA-CH2Cl2 (2 mL, v/v = 1:1) at
r.t. for 1 h, filtered, and washed with CH2Cl2 (1
mL). The filtrate was evaporated to dryness providing 22 mg of 4-(3-phenylquinoxalin-2-yl)benzoic
acid (6a) in 69% yield.LC-MS:
5.70 min, 88% (210 nm), m/z = 327 [M + H+]. ¹H NMR
(400 MHz, DMSO-d
6): δ = 7.36-7.43
(m, 3 H), 7.48-7.50 (m, 2 H), 7.59 (d, J = 8.1,
2 H), 7.90-7.94 (m, 4 H), 8.18-8.20 (m, 2 H),
13.21 (br s, 1 H) ppm. ¹³C NMR (100 MHz,
DMSO-d
6): δ = 128.16,
128.86, 128.90, 128.94, 129.54, 129.78, 129.89, 130.61, 130.80,
131.31, 138.44, 140.39, 140.62, 142.76, 152.35, 153.06, 167.05.
HRMS:
m/z calcd for
C21H15O2N2 [M + H+]:
327.1128; found 327.1125. For further analytical data see: van Es T.
Backeberg OG.
J.
Chem. Soc.
1963,
1371
17
Representative
Experimental Procedure for the Synthesis of Imidazoles
4-[Oxo(phenyl)acetyl]benzoic
acid functionalized Wang resin (4a, 215
mg, 0.20 mmol, loading of 0.93 mmol/g) was suspended in
AcOH (3 mL) and charged with benzaldehyde (420 mg, 20 equiv, 4.00
mmol), and NH4OAc (310 mg, 20 equiv, 4.00 mmol). In case
of 7c 40 equiv benzaldehyde, 40 equiv benzylamine,
and 1.5 equiv NH4OAc was used. The reaction mixture was
heated to 110 ˚C for 16 h. The resin was filtered
and washed successively with 50% aq AcOH, DMF, MeOH, THF,
as well as CH2Cl2. The resin was cleaved with
TFA-CH2Cl2 (2 mL, v/v = 1:1)
at r.t. for 1 h, filtered, and washed with CH2Cl2 (1
mL). The filtrate was evaporated to dryness providing 38 mg of 4-(2,5-diphenyl-1H-imidazol-4-yl)benzoic acid (7a) in 56% yield.
LC-MS:
3.83 min, 69% (210 nm), m/z = 341 [M + H+]. ¹H NMR
(400 MHz, DMSO-d
6): δ = 7.43-7.51
(m, 3 H), 7.52-7.59 (m 5 H), 7.67 (d, J = 8.60
Hz, 2 H), 7.96 (d, J = 8.60
Hz, 2 H), 8.13 (d, J = 7.45
Hz, 2 H) ppm; two protons not observed in this spectrum. ¹³C
NMR (100 MHz, DMSO-d
6): δ = 126.08,
127.64, 128.27, 128.43, 128.54, 128.74, 128.78, 128.89, 129.18,
129.50, 129.63, 129.89, 130.12, 130.99, 145.24, 166.83. HRMS: m/z calcd for C22H17O2N2 [M + H+]: 341.1285;
found: 341.1280.
