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DOI: 10.1055/s-0029-1218551
A New Entry to Benzo[4,5]furo[3,2-b]pyridines via N-(Benzofuran-3-yl)iminophosphorane
Publikationsverlauf
Publikationsdatum:
10. Dezember 2009 (online)
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Abstract
Mild thermal reaction of enones with N-(benzofuran-3-yl)iminophosphorane, newly prepared by Staudinger reaction of 3-azidobenzofuran with triphenylphosphine, provides a synthetic entry to virtually unknown benzo[4,5]furo[3,2-b]pyridines via a tandem aza-Wittig-electrocyclization process.
Key words
iminophosphoranes - azides - aza-Wittig - electrocyclization - benzofuropyridines
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1a
Kovtunenko VO. In Drug Methods Acting on the Central Nervous System Perun; Kiev: 1997. p.373 -
1b
Silvermann RB. In The Organic Chemistry of Drug Design and Drug Action 2nd ed: Elsevier Academic Press; New York: 2004. p.617 - 2
Wakelin LPG.Waring MJ. In Comprehensive Medicinal ChemistrySammes PG. Pergamon Press; Oxford: 1990. p.703 -
3a
Venkat RG,Qi L,Pierce M,Robbins PB,Sahasrabudhe SR, andSelliah R. inventors; WO 2007076085. ; Chem. Abstr. 2007, 147, 143456 -
3b
Burstein HJ.Overmoyer B.Gelman R.Silverman P.Savoie J.Clarke K.Dumadag L.Younger J.Ivy P.Winer EP. Invest. New Drugs 2007, 25: 161 -
3c
Brachwitz K.Hilgeroth A. Bioorg. Med. Chem. Lett. 2002, 12: 411 -
3d
Voigt B.Meijer L.Lozach O.Schaechtele C.Totzke F.Hilgeroth A. Bioorg. Med. Chem. Lett. 2005, 15: 823 -
3e
Xie Y,Zhang G,Wang X,Gray NS, andLiu Y. inventors; WO 2007021795. ; Chem. Abstr. 2007, 146, 274386 - Selected examples:
-
4a
Yoon WS.Lee JS.Kang SK.Ha DC.Ha JD. Tetrahedron Lett. 2009, 50: 4492 -
4b
Yue WS.Li JJ. Org. Lett. 2002, 4: 2201 -
4c
Mukhanova TI.Alekseeva LM.Kuleshova EF.Grank VG. Mendeleev Commun. 1993, 4: 146 -
4d
Jaen JC.Wise LD. J. Heterocycl. Chem. 1987, 24: 1317 -
4e
Ueki A,Kawakubo H,Okazaki K, andHase T. inventors; JP 01100172. ; Chem. Abstr. 1989, 111, 194745 -
4f
Klioze SS. inventors; EP 100046 A1. ; Chem. Abstr. 1984, 101, 55087 -
4g
Boigegrain R,Gachon M,Maffrand JP, andMaire G. inventors; DE 2812950. ; Chem. Abstr. 1979, 90, 23019 -
5a
Iaroshenko VO.Wang Y.Zhang B.Volochnyuk D.Sosnovskikh VY. Synthesis 2009, 2393 -
5b
Iaroshenko VO.Groth U.Kryvokhyzha NV.Obeid S.Tolmachev AA.Wesh T. Synlett 2008, 343 -
5c
Degl’Innocenti A.Funicello M.Scafato P.Spagnolo P. Tetrahedron Lett. 1997, 38: 2171 -
5d
Stolle WAW.Marcelis ATM.Koetsier A.van der Plas HC. Tetrahedron 1989, 45: 6511 - 7 Tricycle 3a was
originally reported in low yield via a troublesome six-step sequence
from an N-(aryloxy)-pyridinium salt,
see:
Abramovitch RA.Inbasekaran MN.Kato S.Radzikowska TA.Tomask P. J. Org. Chem. 1983, 48: 690 - For leading reviews on the chemistry of iminophosphoranes and their use in aza-Wittig electrocyclization reactions, see:
-
8a
Wamhoff H.Richard G.Stolben S. Adv. Heterocycl. Chem. 1995, 64: 159 -
8b
Molina P.Vilaplana MJ. Synthesis 1994, 1197 -
8c
Fresneda P.Molina P. Synlett 2004, 1 -
8d
Funicello M.Spagnolo P. In Targets in Heterocyclic Systems Vol. 8:Attanasi OA.Spinelli D. Società Chimica Italiana; Roma: 2004. p.274 - Selected examples:
-
9a
Molina P.Pastor A.Vilaplana MJ. J. Org. Chem. 1996, 61: 8094 -
9b
Kobayashi T.Nitta M. Chem. Lett. 1981, 1459 -
9c
Iino Y.Nitta M. Bull. Chem. Soc. Jpn. 1988, 61: 2235 -
9d
Molina P.Pastor A.Vilaplana MJ. Tetrahedron Lett. 1993, 34: 3773 -
9e
Molina P.Pastor A.Vilaplana MJ.Foces-Foces C. Tetrahedron 1995, 51: 1265 -
10a
Degl’Innocenti A.Funicello M.Scafato P.Spagnolo P.Zanirato P. J. Chem. Soc., Perkin Trans. 1 1996, 2561 -
10b
Bonini C.Chiummiento L.Funicello M.Spagnolo P. Tetrahedron 2000, 56: 1517 -
10c
Bonini C.D’Auria M.Funicello M.Romaniello G. Tetrahedron 2002, 58: 3507 -
10d
Bonini C.Funicello M.Scialpi R.Spagnolo P. Tetrahedron 2003, 59: 7515 - 11
Bonini C.Funicello M.Spagnolo P. Synlett 2006, 1574 - 12
Foresti E.Spagnolo P.Zanirato P. J. Chem. Soc., Perkin Trans. 1 1989, 1354 - 13
Tamura Y.Chun MW.Kwon S.Bayomi SM.Okada T.Ikeda M. Chem. Pharm. Bull. 1978, 26: 3515 -
14a
Unlike aryl azides, the (electron-rich) five-membered heteroaryl counterparts are usually hardly available from corresponding amines via diazonium salts.
-
14b For the first report of
azido-group-transfer reaction with thiophenes and benzothiophenes,
see:
Spagnolo P.Zanirato P. J. Org. Chem. 1978, 43: 3539 -
14c For original general information on
the synthesis of five-membered heteroaromatic azides, see:
Funicello M.Spagnolo P.Zanirato P. Acta Chem. Scand. 1993, 47: 231
References and Notes
The 2- and 3-amines derived from electron-rich,
five-membered heteroaromatic compounds usually are highly unstable
compounds, unless electron-withdrawing substituents are present,
and therefore find uncommon
use in synthetic annulation
processes.
Synthesis of 3-Azidobenzofuran (4) via Azido-Group-Transfer Reaction To a solution of 3-bromobenzofuran (1.07 mmol) in dry Et2O (6 mL) n-BuLi (1.6 M in hexane, 1.07 mmol) was added at -70 ˚C under a stream of nitrogen. After 1 h, tosyl azide (1.07 mmol in 4 mL of dry Et2O) was added dropwise, and the mixture was stirred for 5 h at -70 ˚C. The resulting yellow mixture was slowly led to r.t. and then treated with an aq solution of sodium pyrophosphate (5 mL, 1.07 mmol). After stirring for 30 min, the eventual reaction mixture was extracted with Et2O and then with EtOAc; the collected organic layers were dried over Na2SO4 and finally evapo-rated in vacuo. Column chromatography of the crude on a Florisil column using PE as eluant isolated the title azide (0.71 mmol, 66%) as yellow thick oil. Physical and IR and NMR spectral data were fully consistent with those originally reported.
16
Synthesis of Triphenyliminophosphorane
5
3-Azidobenzofuran (4, 1
mmol) in dry Et2O (3 mL) was slowly added to a solution
of Ph3P (1 mmol) in dry Et2O (3 mL) at 0 ˚C
under a stream of nitrogen. The mixture was stirred at 0 ˚C
for 3 h and then at r.t. for an additional 1 h. Removal of the solvent
in vacuo afforded the title imino-phosphorane as yellow thick oil
in 95% yield. ¹H NMR (500 MHz, CDCl3): δ = 7.23-7.70
(m, 16 H), 7.20 (t, J = 10.5
Hz, 2 H), 7.03 (d, J = 9.0
Hz, 1 H), 6.94 (d, J = 8.0
Hz, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 132.78,
132.71, 132.59, 132.51, 131.99, 131.75, 128.77, 128.67, 128.53,
128.44, 123.57, 121.18, 120.05, 119.84, 110.88, 110.67.
Synthesis of Benzofuropyridines 3a-f: Typical Procedure A mixture of iminotriphenylphosphorane 5 (1 mmol) and methyl trans-4-oxo-2-pentenoate (6e, 1 mmol) in dry toluene (5 mL) was stirred at 90 ˚C for ca. 20 h under a stream of nitrogen. After cooling, the solvent was removed in vacuo, and the resultant crude was purified on a silica gel column by progressive elution with PE-EtOAc mixtures to give the benzofuropyridine 3e in 80% yield as a dark-yellow thick oil. ¹H NMR (500 MHz, CDCl3): δ = 8.27 (d, J = 7.0 Hz, 1 H), 7.76 (s, 1 H), 7.72 (d, J = 8.0 Hz, 1 H), 7.62 (t, J = 7.0 Hz, 1 H), 7.47 (t, J = 8.0 Hz, 1 H), 4.10 (s, 3 H), 2.81 (s, 3 H). ¹³C NMR (125 MHz, CDCl3): δ = 165.7, 164.3, 156.2, 153.6, 133.5, 130.2, 126.2, 124.2, 121.7, 118.6, 114.1, 113.2, 52.7, 29.7. MS (EI): m/z = 241 [M]. The parent benzofuropyridine 3a had spectral data consistent with those previously reported.4b The hitherto unknown benzofuro-pyridines 3b-d,f were identified on the basis of ¹H NMR, ¹³C NMR, and MS spectral data.
18Reactions of enones with (benzothien-3-yl)iminophos-phoranes bearing methyl substituent(s) on phosphorus were shown to form b-fused pyridines due to aza-Wittig electrocyclization along with those due to opposite regiochemistry, see ref. 10b,c.
19Replacement of phenyl with electron-donating methyl group(s) on phosphorus could enhance the reactivity of previous (benzothien-2-yl)- and, especially, (benzothien-3-yl)imino-phosphoranes with enones, see ref. 10b,c.