S. J. Pridmore et al. / Tetrahedron Letters 48 (2007) 5111–5114
5113
ediols were converted into the required furan derivatives
with good to excellent selectivities with ruthenium dihy-
dride [Ru(PPh3)3(CO)H2] 4 and Xantphos 5 system,
which also displayed good functional group tolerance21
(Table 4).
OH
1. -BuLi (2 equiv.)
n
THF, -78 °C
OH
R1
R2
OH
R1
O
H
R2
6
1
7
In summary, we have shown the use of alkynediols as
attractive starting materials for the synthesis of 2,5-
disubstituted furans. The use of 1,4-alkynediols can
overcome some of the problems often associated with
the classical Paal–Knorr synthesis such as availability
and stability of the 1,4-diketone substrates. Using ruthe-
nium dihydride [Ru(PPh3)3(CO)H2] 4 and Xantphos 5
system with an organic acid co-catalyst, various furans
could be made in one tandem reaction.
Scheme 3. Preparation of 1,4-alkynediols.
Table 3. Alkynediols synthesised (isolated yields)
Diol
R1
R2
Yield (%)
1a
1b
1c
1d
1e
1f
Me
Me
Me
Me
Me
H
Ph
82
65
63
78
51
52
74
35
57
76
59
58
58
48
55
64
44
67
70
38
22
nPr
iPr
tBu
CH2CH2Ph
Ph
tBu
Acknowledgement
1g
1h
1i
Ph
Ph
CH2CH2Ph
m-ClC6H4
o-BrC6H4
p-MeC6H4
m-MeC6H4
o-MeC6H4
p-FC6H4
p-NCC6H4
p-MeOC6H4
p-O2NC6H4
p-MeO2CC6H4
Naphthyl–
2-Furyl–
2-Thienyl–
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
Me
The authors wish to thank the EPSRC for funding.
1j
1k
1l
References and notes
1m
1n
1o
1p
1q
1r
1s
1t
1. (a) Shipman, M. Contemp. Org. Synth. 1995, 2, 1; (b)
Lipshutz, B. H. Chem. Rev. 1986, 86, 795.
2. Patrick, G. L. An Introduction to Medicinal Chemistry, 2nd
ed.; Oxford University Press: Oxford, 2001; p 581.
3. (a) Paal, C. Chem. Ber. 1884, 17, 2756; (b) Knorr, L.
Chem. Ber. 1884, 17, 2863.
4. Cormier, R. A.; Francis, M. D. Synth. Commun. 1981, 11,
365.
1u
5. Cornforth, J. A. J. Chem. Soc. 1958, 1310.
6. Seyferth, H. E. Chem. Ber. 1968, 101, 619.
7. For
a recent review on transition metal catalysed
Table 4. Conversion of alkynediols into furansa
approaches to the synthesis of furans and pyrroles, see:
Patil, N. T.; Yamamoto, Y. ARKIVOC 2007, x, 121.
8. Ziegler, F. E.; Jeroncic, L. O. J. Org. Chem. 1991, 56,
5774.
9. Sheng, H.; Lin, S.; Huang, Y. Synthesis 1987, 1022.
10. Fukuda, Y.; Shiragami, H.; Utimoto, K.; Nozaki, H. J.
Org. Chem. 1991, 56, 5816.
O
R2
+
R1
R1
R2
O
O
3
2
Diol
Conversion (%)
Ketone 2 (%)
Furan 3 (%)
11. Hashimi, A. S. K. Angew. Chem., Int. Ed. Engl. 1995, 107,
1749.
12. Cacchi, S.; Fabrizi, G.; Moro, L. J. Org. Chem. 1997, 62,
5327.
13. Lu, X.; Ji, J.; Ma, D.; Shen, W. J. Org. Chem. 1991, 56,
5774.
14. Lu, X.; Ji, J. J. Chem. Soc., Chem. Commun. 1993, 764.
15. Edwards, M. G.; Jazzar, R. F. R.; Paine, B. M.; Shermer,
D. J.; Whittlesey, M. K.; Williams, J. M. J.; Edney, D. D.
Chem. Commun. 2004, 90.
16. Edwards, M. G.; Williams, J. M. J. Angew. Chem., Int. Ed.
2002, 41, 4740; Black, P. J.; Cami-Kobeci, G.; Edwards,
M. G.; Slatford, P. A.; Whittlesey, M. K.; Williams, J. M.
J. Org. Biomol. Chem. 2006, 4, 116.
17. For a recent review, see Gladiali, S.; Alberico, E. Chem.
Soc. Rev. 2006, 35, 226.
18. Slatford, P. A.; Whittlesey, M. K.; Williams, J. M. J.
Tetrahedron Lett. 2006, 47, 6787.
19. Freixa, Z.; van Leeuwen, P. W. N. M. Dalton Trans. 2003,
1890.
1a
1b
1c
1d
1e
1f
100
95b
15
22b
15b
7b
9b
4
20
24
23
18
19
19
23
17
12
20
10
0
85
73b
79b
93b
91b
96
80
76
77
82
81
81
77
83
88
80
40
100
82
94b
100b
100b
100
100c
100c
100
100
100c
100c
100
100
100
100
50c
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
1s
1t
100
100
100
100
18
19
22
81
78
20. Procedure for synthesis of 1-phenylpent-2-yne-1,4-diol.
Butyn-2-ol (5 mL, 4.47 g, 65 mmol) was added to anhy-
drous THF (50 mL) under an Ar atmosphere and cooled
to ꢀ78 ꢁC. n-BuLi (10 N) (12.75 mL, 130 mmol) was
added dropwise and the reaction mixture stirred at
1u
a Using benzoic acid (5 mol %), reactions analysed by 1H NMR.
b Analysed by GC.
c Using propanoic acid (5 mol %).