References
1 Current address: Constellation Pharmaceuticals,
Cambridge, MA, USA; alex.gagnon@constellationpharma.com.
For an excellent review on molecular
interactions in medicinal chemistry, see:
2a
Bissantz C.
Kuhn BK.
Stahl M.
J.
Med. Chem.
2010,
53:
5061
2b See also: Gagnon A.
Duplessis M.
Fader L.
Org. Prep. Proced. Int.
2010,
42:
1
3 See: Han C.
Buchwald SL.
J. Am. Chem. Soc.
2009,
131:
7532 ; and references cited therein
4a
Luo X.
Zhang H.
Duan H.
Liu Q.
Zhu L.
Zhang T.
Lei A.
Org.
Lett.
2007,
9:
4571
4b
Zhang H.
Lu X.
Wongkhan K.
Duan H.
Li Q.
Zhu L.
Wang J.
Batsanov AS.
Howard JAK.
Marder TB.
Lei A.
Chem.
Eur. J.
2009,
15:
3823
5a
Luh T.-Y.
Leung M.-K.
Wong K.-T.
Chem. Rev.
2000,
100:
3187
5b
Frisch AC.
Beller M.
Angew. Chem. Int.
Ed.
2005,
44:
674
6a
Kondolff I.
Doucet H.
Santelli M.
Tetrahedron
2004,
60:
3813
6b
Wang B.
Sun H.-X.
Sun Z.-H.
Lin G.-Q.
Adv. Synth. Catal.
2009,
351:
415
6c
Wang B.
Sun H.-X.
Sun Z.-H.
Eur.
J. Org. Chem.
2009,
3688
6d
Chemler SR.
Trauner D.
Danishefsky SJ.
Angew. Chem. Int. Ed.
2001,
40:
4544
7a
Manolikakes G.
Muñoz Hernandez C.
Schade MA.
Metzger A.
Knochel P.
J. Org.
Chem.
2008,
73:
8422
7b
Liu J.
Deng Y.
Wang H.
Zhang H.
Yu G.
Wu B.
Zhang H.
Li Q.
Marder TB.
Yang Z.
Lei A.
Org. Lett.
2008,
10:
2661
7c
Liu Q.
Duan H.
Luo X.
Tang Y.
Li G.
Huang R.
Lei A.
Adv. Synth. Catal.
2008,
350:
1349
7d
Wang H.
Liu J.
Deng Y.
Min T.
Yu G.
Wu X.
Yang Z.
Lei A.
Chem.
Eur. J.
2009,
15:
1499
8a
Kondolff I.
Feuerstein M.
Doucet H.
Santellli M.
Tetrahedron
2007,
63:
9514
8b
Hamaguchi H.
Uemura M.
Yasui H.
Yorimitsu H.
Oshima K.
Chem. Lett.
2008,
37:
1178
9a
Shenglof M.
Gelman D.
Heymer B.
Schumann H.
Molander GA.
Blum J.
Synthesis
2003,
302
9b
Pena MA.
Pérez Sestelo J.
Sarandeses LA.
Synthesis
2005,
485
9c
Chupak LS.
Wolkowski JP.
Chantigny YA.
J. Org. Chem.
2009,
74:
1388
For reviews on bismuth chemistry,
see:
10a
Finet J.-P.
Chem.
Rev.
1989,
89:
1487
10b
Suzuki H.
Ikegami T.
Matano Y.
Synthesis
1997,
249
11a
Barton DHR.
Ozbalik N.
Ramesh M.
Tetrahedron
1988,
44:
5661
11b
Rao MLN.
Yamazaki O.
Shimada S.
Tanaka T.
Suzuki Y.
Tanaka M.
Org. Lett.
2001,
3:
4103
11c
Shimada S.
Yamazaki O.
Tanaka T.
Rao MLN.
Suzuki Y.
Tanaka M.
Angew. Chem. Int. Ed.
2003,
42:
1845
11d
Kang S.-K.
Ryu H.-C.
Kim JW.
Synth. Commun.
2001,
31:
1021
11e
Kang S.-K.
Ryu H.-C.
Hong Y.-T.
Kim M.-S.
Lee S.-W.
Jung J.-H.
Synth. Commun.
2001,
31:
2365
11f
Moiseev DV.
Malysheva YB.
Shavyrin AS.
Kurskii YA.
Gushchin AV.
J. Organomet.
Chem.
2005,
690:
3652
11g
Rao MLN.
Banerjee D.
Jadhav DN.
Tetrahedron Lett.
2007,
48:
2707
11h
Rao MLN.
Banerjee D.
Jadhav DN.
Tetrahedron Lett.
2007,
48:
6644
For the coupling of methyl groups
using dialkoxymethylbismuth and diarylmethylbismuth species, see:
12a
Rao MLN.
Shimada S.
Tanaka M.
Org. Lett.
1999,
1:
1271
12b
Rao MLN.
Shimada S.
Yamazaki O.
Tanaka M.
J. Organomet.
Chem.
2002,
659:
117
12c
Yamazaki O.
Tanaka T.
Shimada S.
Suzuki Y.
Tanaka M.
Synlett
2004,
1921
13
Gagnon A.
St-Onge M.
Little K.
Duplessis M.
Barabé F.
J.
Am. Chem. Soc.
2007,
129:
44
14
Gagnon A.
Duplessis M.
Alsabeh P.
Barabé F.
J. Org. Chem.
2008,
73:
3604
15 The organomagnesium reagents were
titrated before use using diphenylditelluride: Aso Y.
Yamashita H.
Otsubo T.
Ogura F.
J. Org. Chem.
1989,
54:
5627
16
General Procedure
for the Preparation of 4, 6a-o, and 8
In a round-bottom
flask equiped with a condenser and sparged with argon, BiCl3 (173
mg, 0.55 mmol) was suspended in anhydrous THF (3 mL) and cooled
to 0 ˚C. The organomagnesium reagent (1.705 mmol, THF or
Et2O solution) was slowly added dropwise, and the solution
was stirred at 0 ˚C for 30 min, warmed to r.t., and then
heated at 65 ˚C for an additional 30 min. The reaction
mixture was cooled to r.t. and diluted with DMF (1 mL). A DMF solution of
the aryl or heteroaryl halide or pseudo halide (0.500 mmol in 4
mL) was then added, followed by K2CO3 or Cs2CO3 (1.00
mmol) and Pd(PPh3)4 (28 mg, 0.025 mmol). The solution
was degassed by bubbling argon during 15 min, and then stirred at
110 ˚C for 18 h. The reaction mixture was cooled to r.t.,
diluted with sat. aq NaHCO3 (10 mL) and extracted with
EtOAc (2 × 10 mL). The combined organic phases
were washed with brine (3 × 10 mL), dried
over Na2SO4, filtered, and concentrated under
reduced pressure. The residue was purified by flash chromatography
(1% to 15% EtOAc-hexanes or Et2O-hexanes)
to afford the desired products 4, 6a-o,
and 8.
Spectral
Data for 6n
R
f
= 0.41 (20% EtOAc-hexanes). ¹H
NMR (400 MHz, CDCl3): δ = 8.81 (d, J = 1.8 Hz,
1 H), 8.08 (d, J = 8.4
Hz, 1 H), 7.94 (s, 1 H), 7.76 (d, J = 8.1
Hz, 1 H), 7.66 (t, J = 8.2 Hz,
1 H), 7.53 (t, J = 7.0
Hz, 1 H), 4.56 (t, J = 5.1
Hz, 1 H), 4.12 (dd, J = 10.0,
5.0 Hz, 2 H), 3.76 (dt, J = 12.5,
2.4 Hz, 2 H), 2.93 (t, J = 7.8
Hz, 2 H), 2.13-2.04 (m, 1 H), 2.02-1.99 (m, 2
H), 1.35 (d, J = 13
Hz, 1 H). ¹³C NMR (100 MHz, CDCl3): δ = 152.5,
147.2, 134.8, 134.7, 129.6, 129.0, 128.6, 127.8, 127.0, 101.4, 67.3,
36.6, 27.7, 26.2. IR (neat): 2959, 2850, 1494, 1378, 1240, 1138,
1082, 1043, 1002 cm-¹. HRMS (EI): m/z calcd for C15H17NO2 [M]:
243.1259; found: 244.1328 [M + H].