7622
J . Org. Chem. 1999, 64, 7622-7624
P r ep a r a tion of â-Am id o Keton es a n d Ald eh yd es via
Am id oa lk yla tion of En a m in es, En ol Silyl Eth er s, a n d Vin yl Eth er s
Alan R. Katritzky,* Yunfeng Fang, and Alina Silina
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received April 9, 1999
Novel syntheses of â-amidoalkyl ketones and aldehydes via amidoalkylations of enamines, silyl
enol ethers, and vinyl ethers with N-(1-benzotriazol-1-ylalkyl)amides are described.
In tr od u ction
â-Amido ketones and â-amido aldehydes are important
as building blocks and intermediates in synthesis: for
example, they are important precursors of 3-amino
alcohols, which are common units in both natural and
synthetic biologically active compounds.1 â-Amido alde-
hydes are a protected form of â-amino aldehydes, key
intermediates in the synthesis, e.g., of aminocyclitols.2
â-Amido aldehydes of type RCH2CH(NHCOR′)CHRCHO
can be prepared by condensation of primary amides with
aliphatic aldehydes (2 equiv) in the presence of trifluo-
romethanesulfonic acid.3 A diastereoselective synthesis
of â-amido aldehydes has been achieved by rearrange-
ment of O-vinyl-N,O-acetals.4
Many approaches to â-amido ketones have been re-
ported. These can be classified according to the bond
formed (Figure 1), and include preparations by formation
of the A bond by acylation of â-amino ketones,5 of the B
bond by Michael addition to an R,â-unsaturated ketone,6a-c
or of the D bond by photolysis of phthalimides.7 However,
most â-amido ketones are prepared by forming the C
bond: (i) Iqbal et al. report a cobalt-catalyzed synthesis
of â-amido ketones from enolates and R-acetoxyamides;8a,b
(ii) under Lewis acid catalysis, 4-acetoxyazetidin-2-one
reacts with various silyl enol ethers to give â-amido
ketones in good to excellent yields;9 (iii) in the presence
of 2.1 equiv of various metallic oxidants, 2-pivaloyl-1-
tributylstannyl-1,2,3,4-tetrahydroisoquinoline converts
diverse silyl enol ethers into â-amido ketones.10
F igu r e 1.
strated N-(1-benzotriazol-1-ylalkyl)amides to be versatile
reagents for the amidoalkylation13 of malonates and
acetoacetates,14 reactive aromatics,15 cyanide anion,16
mercaptans,17 alcohols,18 ammonia,19 ethyl diphenylphos-
phinite anion,20 primary and secondary amines,21 and
triallylstannanes22a,b giving in each case the expected
products. We have previously reported one example that
used an N-(benzotriazol-1-ylmethyl)benzamide to react
with isopropenyl acetate to afford a â-amido ketone in
relatively poor yield.23 We now report applications of
N-(benzotriazol-1-ylalkyl)amides for the synthesis of
â-amido ketones and aldehydes via the amidoalkylation
of enamines, enol silyl ethers, and vinyl ethers.
Resu lts a n d Discu ssion
The amidoalkylation reagents N-(1-benzotriazol-1-yl-
alkyl)amides 1a -j and 2-5, derived from primary or
(11) (a) Zaugg, H. E. Synthesis 1984, 85. (b) Zaugg, H. E. Synthesis
1984, 181.
(12) (a) Bott, K. Angew. Chem., Int. Ed. Engl. 1980, 19, 171. (b)
Danishefsky, S.; Guingant, A.; Prisbylla, M. Tetrahedron Lett. 1980,
21, 2033. (c) Shono, T.; Matsumura, Y.; Tsubata, K. J . Am. Chem. Soc.
1981, 103, 1172. (d) Wanner, K. Th.; Praschak, I. Heterocycles 1989,
29, 29. (e) Kraus, G. A.; Neuenschwander, K. Tetrahedron Lett. 1980,
21, 3841.
Amidoalkylations, which have been used widely in
organic synthesis,11a,b have provided many â-amidocar-
bonyl compounds.12a-e Our previous work has demon-
(1) Barluenga, J .; Viado, A. L.; Aguilar, E.; Fustero, S.; Olano, B. J .
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Chem. 1991, 56, 4439.
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M. Tetrahedron Lett. 1986, 27, 2607.
(15) Katritzky, A. R.; Pernak, J .; Fan, W. Q. Synthesis 1991, 868.
(16) Katritzky, A. R.; Shobana, N.; Harris, P. A. Org. Prep. Proced.
Int. 1992, 121.
(17) Katritzky, A. R.; Takahashi, I.; Fan, W. Q.; Pernak, J . Synthesis
1991, 1147.
(6) (a) Inubushi, Y.; Kikuchi, T.; Ibuka, T.; Tanaka, K.; Saji, I.;
Tokane, K. Chem. Comm. 1972, 1252. (b) J effs, P. W.; Redfearn, R.;
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(22) (a) Katritzky, A. R.; Chang, H. X.; Wu, J . Synthesis 1994, 907.
(b) Pearson, W. H.; Stevens, E. P. Synthesis 1994, 904.
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10.1021/jo990608u CCC: $18.00 © 1999 American Chemical Society
Published on Web 09/11/1999