560
I. M. Lyapkalo et al.
LETTER
Table 1 Synthesis of Alkynes 2 from Aldehydes and Ketones 1 Ac-
dien-2-yl nonaflate. The result is somewhat surprising
since it indicates that the first deprotonation at one of the
distal methyl groups occurs in favour of that adjacent to
the carbonyl in the starting 4-methylpent-3-en-2-one (1u).
cording to Scheme 1 (Z = Nf)a (continued)
Reaction
conditions
Product 2
(isolated yield, %)
Starting material 1
O
In conclusion, we found that nonafluorobutane-1-sulfonyl
fluoride in combination with phosphazene bases16 induces
clean conversion of carbonyl compounds into alkynes.
The combined reagent is applicable to both aldehydes and
ketones thus enabling the hitherto most general one-pot
synthesis of acetylenes by formal elimination of H2O from
enolisable carbonyl functionality.
P1-base,b DMF,
4-MeO2CC6H4C
CH
6 h
4-MeO2CC6H4
2o (97)
1o
O
P1-base, DMF,
19 h
3-MeOC6H4C CH
3-MeOC6H4
2p (80)
1p
O
O
O
P1-base, DMF,
48 h
Acknowledgment
·
O
O
Generous donation of nonafluorobutane-1-sulfonyl fluoride by
Lanxess Deutschland GmbH is gratefully acknowledged.
2q (63)
1q
O
O
NfF (2.4 equiv),
P1-base (4.6 equiv),b
DMF, 15 h
·
·
References and Notes
(1) Modern Acetylene Chemistry; Stang, P. J.; Diederich, F.,
Eds.; VCH: Weinheim, 1995.
1r (78)
2s (49)
1r
1s
O
(2) (a) Nicolaou, K. C.; Dai, W.-M. Angew. Chem., Int. Ed.
Engl. 1991, 30, 1387; Angew. Chem. 1991, 103, 1453.
(b) Nicolaou, K. C.; Smith, A. L. The Enediyne Antibiotics,
In Modern Acetylene Chemistry; Stang, P. J.; Diederich, F.,
Eds.; VCH: Weinheim, 1995, 203. (c) Grissom, J. W.;
Gunawardena, G. U.; Klingberg, D.; Huang, D. H.
Tetrahedron 1996, 52, 6453.
(3) Kolb, H. C.; Finn, M. G.; Sharpless, K. B. Angew. Chem. Int.
Ed. 2001, 40, 2004; Angew. Chem. 2001, 113, 2056.
(4) (a) Yashima, E.; Maeda, K.; Okamoto, Y. Nature (London)
1999, 399, 449. (b) Nielsen, M. B.; Diederich, F. Synlett
2002, 544. (c) Liang, Z.; Northrop, B. H.; Zheng, Y.-R.;
Yang, H.-B.; Lee, H. J.; Lee, Y. M.; Park, J. Y.; Chi, K.-W.;
Stang, P. J. J. Org. Chem. 2008, 73, 6580.
(5) Negishi, E.; King, A. O.; Klima, W. L.; Patterson, W.;
Silveira, A. J. Org. Chem. 1980, 45, 2526; the authors
noticed that the procedures involving harsh reagents such as
PCl5, NaNH2, etc. described in earlier literature are of
limited synthetic applicability, see references therein.
(6) (a) Huang, D. F.; Shen, T. Y. Tetrahedron Lett. 1993, 34,
4477. (b) Hong, J. E.; Lee, C.-W.; Kwon, Y.; Oh, D. Y.
Synth. Commun. 1996, 26, 1563.
NfF (2.4 equiv),
P1-base (3.4 equiv),b
DMF, 18 h
NfO
·
HO
O
P1-base,b THF,
18 h
·
N
N
2t (66)
1t
P1-base,b
N-methyl-2-
pyrrolidone, 16 h
O
·
·
2u (55)c
1u
O
P1-base, DMF,
19 h
4-FC6H4C CMe
4-FC6H4
2v (88)
1v
O
P1-base,b DMF,
20 h
PhC CEt
Et
Ph
2w (95)
1w
O
(7) Clasby, M. C.; Craig, D. Synlett 1992, 825.
P1-base,b DMF,
5 h
Ph
·
·
CO2Et
CO2Et
(8) (a) Leclercq, M.; Brienne, M.-J. Tetrahedron Lett. 1990, 31,
3875. (b) A several examples using related 2-chloro-3-
ethylbenzo[d]oxazol-3-ium tetrafluoroborate are also
reported: Tsuji, T.; Watanabe, Y.; Mukaiyama, T. Chem.
Lett. 1979, 481.
(9) A complex, multistep redox transformation involving
n-Bu3SnLi, CBr4, Ph3P, DBU, and Pb(OAc)4 is reported:
Shibasaki, M.; Torisawa, Y.; Ikegami, S. Tetrahedron Lett.
1982, 23, 4607.
(10) Commercially available as a 2 M solution in THF,
pKa = 33.49 in MeCN, see: Schwesinger, R.; Schlemper, H.;
Hasenfratz, C.; Willaredt, J.; Dambacher, T.; Breuer, T.;
Ottaway, C.; Fletschinger, M.; Boele, J.; Fritz, H.; Putzas,
D.; Rotter, H. W.; Bordwell, F. G.; Satish, A. V.; Ji, G. Z.;
Peters, E. M.; Peters, K.; von Schnering, H. G.; Walz, L.
Liebigs Ann. Org. Bioorg. Chem. 1996, 7, 1055.
Ph
2 × (82)
1x
a P-Bases (2.2–2.4 equiv) and NfF (1.2–1.3 equiv) at ambient temper-
ature were employed, unless stated otherwise.14
b The base is added to the precooled mixture of all the other compo-
nents at –10 °C followed by warming to r.t. for 1–2 h.
c The product was isolated by recondensation from the reaction mix-
ture to a small cold (liquid N2) trap.
d Allene Me(CH2)9CH=C=CH2 (ca. 6 mol%) was also detected in the
isolated mixture of 2e and 2e¢.
e No conversion was observed with P1-base even upon heating up to
50 °C.
f THF was removed in vacuum from the solution of P2-base10 in N-me-
thyl-2-pyrrolidone before NfF and 1g were successively added.
(11) Recently, we reported an efficient procedure for purification
of NfF which was employed in synthesis of enol nonaflates
from aldehydes and cyclic ketones, see: Vogel, M. A. K.;
Stark, C. B. W.; Lyapkalo, I. M. Synlett 2007, 2907.
Exclusive formation of the internal enyne, 2-methylpent-
1-en-3-yne (2u)15 instead of expected 4-methylpent-3-en-
1-yne implies the intermediacy of 4-methylpenta-2,4-
Synlett 2009, No. 4, 558–561 © Thieme Stuttgart · New York