Bismuth-triflate-catalyzed Prins-Ritter reaction - An efficient synthesis of 4-amidotetrahydropyrans

Article abstract of DOI:10.1139/V08-080

Bismuth(III) triflate is found to be an effective Lewis acid in catalyzing a three-component reaction of homoallylic alcohol, carbonyl compound, and nitrile at ambient temperature via the Prins-Ritter sequence to furnish 4-amidotetrahydropyrans in high yi

Full text of DOI:10.1139/V08-080

769
Bismuth-triflate-catalyzed Prins–Ritter reaction —
An efficient synthesis of 4-amidotetrahydropyrans
J.S. Yadav, B.V. Subba Reddy, D.N. Chaya, G.G.K.S. Narayana Kumar
Abstract: Bismuth(III) triflate is found to be an effective Lewis acid in catalyzing a three-component reaction of
homoallylic alcohol, carbonyl compound, and nitrile at ambient temperature via the Prins–Ritter sequence to furnish
4-amidotetrahydropyrans in high yields, all with cis selectivity. Spirocyclic 4-amidotetrahydropyrans are obtained in
case of cyclic ketones.
Key words: Prins cyclization, bismuth(III) triflate, homoallyl alcohol, 4-amidotetrahydropyrans.
Résumé : On a trouvé que le triflate de bismuth(III) agit comme acide de Lewis efficace dans la catalyse de la réac-
tion à trois composantes d’un alcool homoallylique, d’un composé carbonylé et d’un nitrile à la température ambiante,
par le biais d’une séquence de Prins–Ritter, qui conduit à la formation de 4-amidotétrahydropyranes, avec des rende-
ments élevés et une sélectivité complètement cis. Dans les cas où le produit de départ est une cétone cyclique, le pro-
duit obtenu est un 4-amidotétrahydropyrane spirocyclique.
Mots-clés : cyclisation de Prins, bismuth(III), triflate, alcool homoallylique, 4-amidotétrahydropyranes.
[Traduit par la Rédaction] Yadav et al. 773
Introduction
Scheme 1.
Recently, multicomponent one-pot synthesis has received
considerable attention because of its wide range of applica-
tions in medicinal chemistry for the production of structural
scaffolds and combinatorial libraries in drug discovery (1).
The 4-aminotetrahydropyran ring system is found in many
biologically active natural products, such as ambruticins VS,
glycamino acid, and others (2, 3). Tetrahydropyran deriva-
tives are usually prepared by the Prins cyclization using acid
catalysis (4, 5) or by intramolecular hetero-Michael reaction
(6). However, the use of Ritter amidation to terminate Prins
cyclization is scarce (7); hence, an efficient and practical
methodology for the Prins–Ritter-type reaction would be of
great importance for the synthesis of natural products (8).
Lanthanide triflates are unique Lewis acids that are cur-
rently of great interest (9). The high catalytic activity, low
toxicity, moisture and air tolerance, and their recyclability
make lanthanide triflates attractive alternatives to conven-
tional Lewis acids (10). However, lanthanide triflates are
rather expensive and their use in large-scale synthesis is lim-
ited. Therefore, cheaper and more efficient catalysts are de-
sirable. In this direction, bismuth triflate has evolved as
remarkable Lewis acid catalyst for effecting various organic
transformations (11). Compared with lanthanide triflates,
bismuth triflate is cheap and is easy to prepare, even on a
multi-gram scale, from commercially available bismuth ox-
ide and triflic acid (12). However, there have been no re-
ports on the use of bismuth triflate for the synthesis of
tetrahydropyrans.
Results and discussion
In this article, we describe a direct and efficient method
for the synthesis of 4-amidotetrahydropyrans via the Prins–
Ritter sequence using bismuth triflate. In a preliminary
study, 3-phenylpropanal (1) was treated with but-3-en-1-ol
(2) in acetonitrile in the presence of 10 mol% of bismuth
triflate. The reaction went to completion in 4.5 h at room
temperature, and the product 4-acetamidotetrahydropyran 3a
was obtained, instead of tetrahydropyranyl-4-triflate, in 93%
yield with cis selectivity (Scheme 1).
This result encouraged us to study the reaction with
various aldehydes, homoallylic alcohols, and nitriles. Inter-
estingly, 3-buten-1-ol reacted smoothly with cyclohexane-
carboxaldehyde, isobutyraldehyde, trans-cinnamaldehyde,
1-naphthaldehyde, 3,4-dichlorobenzaldehyde, 3,4,5-trimeth-
oxybenzaldehyde, and m-nitrobezaldehyde in acetonitrile to
produce the corresponding 4-acetamidotetrahydropyrans in
high yields (Table 1, entries b–h,). The substituted homo-
allylic alcohols like 1-phenylbut-en-1-ol and 1-cyclo-
hexylbut-en-1-ol also participated well in this transformation
(Table 1, entries o and p). This reaction proceeded well even
with cyclic ketones such as cyclopentanone, cyclohexanone,
and 4-phenyl-1-cyclohexanone to give spirocyclic-4-acet-
Received 20 February 2008. Accepted 18 April 2008.
Published on the NRC Research Press Web site at
canjchem.nrc.ca on 17 June 2008.
J.S. Yadav,1 B.V. Subba Reddy, D.N. Chaya, G.G.K.S.
Narayana Kumar. Division of Organic Chemistry, Indian
Institute of Chemical Technology, Hyderabad 500 007, India.
1Corresponding author (e-mail: yadavpub@iict.res.in).
Can. J. Chem. 86: 769–773 (2008)
doi:10.1139/V08-080
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Can. J. Chem. Vol. 86, 2008
Table 1. Preparation of 4-amidotetrahdyropyrans via the Prins–Ritter reaction sequence.
1
aAll products were characterized by H NMR, 13C NMR, IR, and mass spectroscopy.
bIsolated and unoptimized yields.
Scheme 2.
amidotetrahydropyrans comparably in good yields (Table 1,
entries i–k; Scheme 2).
The reaction succeeded with other nitriles such as 2-
phenyl acetonitrile, 3,3-dimethylbutanenitrile, and benzonitrile
(Table 1, entries l–n). In the absence of bismuth triflate, the
© 2008 NRC Canada

Yadav et al.
771
Scheme 3.
reaction did not proceed even after a long reaction time
(16 h). The reactions were clean, and the products were ob-
tained at room temperature in excellent yields and with high
diastereoselectivity as determined from the NMR spectra of
the crude products. Only one diastereoisomer was obtained
in each case, the structure of which was confirmed on the
basis of coupling constants and also by nOe experiments
(8e). The formation of the products could be explained by
hemi-acetal formation followed by Prins cyclization and
subsequent Ritter amidation (Scheme 3).
A tentative reaction mechanism to realize the cis selectiv-
ity could be explained by assuming the formation of an (E)-
oxocarbenium ion via a chairlike transition state, which has
an increased stability relative to the open oxocarbenium ion
owing to delocalization. The optimal geometry for this
delocalization places the hydrogen atom at C-4 in a pseudo-
axial position, which favours equatorial attack of the
nucleophile (13). The effects of various metal triflates such
as In(OTf)3, Yb(OTf)3, Sm(OTf)3, Dy(OTf)3, and Ce(OTf)3
were examined in this reaction. Of these, bismuth triflate
was found to be efficient in terms of conversion. The scope
and generality of this process is illustrated with respect to
various carbonyl compounds, homoallylic alcohols, and
nitriles, and the results are presented in Table 1. It is note-
worthy to highlight that both aromatic and aliphatic sub-
strates worked well for this transformation.
General procedure
A mixture of but-3-en-1-ol (1 mmol), 3-phenylpropanal
(1.2 mmol), and bismuth triflate (10 mol%) in acetonitrile
(5 mL) was stirred at 23 °C for a specified time (Table 1).
After completion of the reaction as indicated by TLC, the re-
action mixture was quenched with water and extracted with
ethyl acetate (2 × 10 mL). The combined organic layers
were dried over anhyd. Na2SO4. Removal of solvent fol-
lowed by purification on silica gel (Merck, 100–200 mesh,
ethyl acetate/hexane, 4:6) gave pure 4-amidotetrahydropyran.
The products thus obtained were characterized by IR and
NMR spectroscopy. Characterization data was found to be
consistent with that of authentic samples (6).
a: N-(2-phenethyltetrahydro-2H-4-pyranyl)acetamide
Pale yellow solid, mp 90–92 °C. IR (KBr) ν: 3308, 2923,
2852, 1648, 1543, 1368, 1083, 946, 745 cm–1. 1H NMR
(300 MHz, CDCl3) δ: 1.26 (m, 2H), 1.31 (dq, 1H, J = 4.2,
12.2 Hz), 1.36 (q, 1H, J = 12.0 Hz), 1.85 (t, 2H, J = 7.5 Hz),
1.93 (s, 3H), 2.66 (ddt, 1H, J = 2.2, 4.2, 12.0 Hz), 2.74 (ddq,
1H, J = 2.2, 12.0, 12.0 Hz), 3.28 (m, 1H), 3.44 (dt, 1H, J =
1.5, 12.0 Hz), 3.89 (m, 1H), 4.13 (m, 1H), 5.28 (d, 1H, J =
8.3 Hz), 7.07–7.26 (m, 5H). 13C NMR (75 MHz, CDCl3) δ:
23.1, 31.4, 32.5, 37.7, 38.3, 45.9, 66.3, 75.4, 125.6, 127.8,
128.1, 141.7, 169.5. LC-MS: m/z (%): (M + Na) 270. HR-
MS calcd. for C15H21NO2Na: 270.1469. Found: 270.1478.
b: N-(2-cyclohexyltetrahydro-2H-4-pyranyl)acetamide
Colourless solid, mp 148–150 °C. IR (KBr) ν: 3280,
3089, 2944, 2930, 2822, 1648, 1543, 1422, 1373, 1091, 966,
804 cm–1.1H NMR (300 MHz, CDCl3) δ: 0.89–1.38 (m,
10H), 1.56–1.90 (m, 5H), 1.93 (s, 3H), 3.04 (m, 1H), 3.41
(dt, 1H, J = 2.0, 12.0 Hz), 3.86 (m, 1H), 3.90 (m, 1H), 5.36
(d, 1H, J = 7.5 Hz). 13C NMR (75 MHz, CDCl3) δ: 169.4,
80.9, 66.2, 46.4, 35.6, 32.8, 32.7, 28.6, 28.4, 25.1, 23.2. LC-
Conclusion
In summary, we described a novel and efficient Prins–
Ritter reaction to produce highly substituted 4-amidotetrahy-
dropyrans in high yields, all with cis selectivity. The use of
inexpensive and readily available bismuth triflate makes this
procedure simple, convenient, and practical. In addition to
its simplicity, efficiency, and milder reaction conditions, this
method provides an easy access for 4-amidotetrahydropyran
derivatives in a single-step operation.
MS: m/z (%): (M
+ Na) 248. HR-MS calcd. for
C13H23NO2Na: 248.1626. Found: 248.1636.
c: N-(2-isopropyltetrahydro-2H-4-pyranyl)acetamide
Colourless solid. mp 74–76 °C. IR (KBr) ν: 3320, 2928,
2838, 1412, 1370, 1256, 1140, 1088, 1046, 986, 876 cm–1.
1H NMR (300 MHz, CDCl3) δ: 0.88 (d, 3H, J = 6.7 Hz),
0.91 (d, 3H, J = 6.7 Hz), 1.06 (m, 1H), 1.23–1.42 (m, 2H),
1.64 (m, 1H), 1.76–1.93 (m, 1H), 1.94 (s, 3H), 3.01 (dq, 1H,
J = 1.5, 6.7 Hz), 3.41 (dt, 1H, J = 1.5, 12.0 Hz), 3.84–4.00
(m, 2H), 6.47 (d, 1H, J = 7.5 Hz). 13C NMR (75 MHz,
CDCl3) δ: 169.4, 81.4, 66.4, 46.3, 35.1, 32.8, 32.7, 23.1,
18.2, 18.0. LC-MS: m/z: (M + Na) 208. HR-MS calcd. for
C10H19NO2Na: 208.1313. Found: 208.1322.
Experimental
Melting points were recorded on Buchi R-535 apparatus
and are uncorrected. IR spectra were recorded on a
PerkinElmer FTIR 240-c spectrophotometer using KBr op-
1
tics. H, 13C NMR spectra were recorded on Gemini-200
spectrometer in CDCl3 using TMS as internal standard.
Mass spectra were recorded on a Finnigan MAT 1020 mass
spectrometer operating at 70 eV. TLC was monitored on
0.25 mm pre-coated silica-gel plates (60F-254).
© 2008 NRC Canada

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Can. J. Chem. Vol. 86, 2008
4.49 (dd, 1H, J = 2.0, 11.2 Hz), 5.23 (d, 1H, J = 7.0 Hz),
7.50–8.08 (m, 4H). 13C NMR (75 MHz, CDCl3) δ: 169.4,
148.2, 144.0, 131.7, 129.1, 122.3, 120.5, 77.1, 66.9, 46.1,
40.4, 32.2, 23.2. LC-MS: m/z: (M + Na) 287. HR-MS calcd.
for C18H26O2Na: 287.1007. Found: 287.1010.
d: N-2-[2-phenyl-(E)-1-ethenyl]tetrahydro-2H-4-
pyranylacetamide
Yellow solid, mp 114–116 °C. IR (KBr) ν: 3294, 2956,
2926, 2230, 1648, 1553, 1366, 1087, 1042, 802, 730 cm–1.
1H NMR (300 MHz, CDCl3) δ: 1.18–1.50 (m, 2H), 1.94 (m,
1H), 1.98 (s, 3H), 2.13 (m, 1H), 3.60 (dt, 1H, J = 1.5,
12.0 Hz), 4.02–4.15 (m, 3H), 5.37 (d, 1H, J = 6.8 Hz), 6.14
(dd, 1H, J = 5.3, 15.8 Hz), 6.57 (d, 1H, J = 15.8 Hz), 7.18–
7.40 (m, 5H). 13C NMR (75 MHz, CDCl3) δ: 169.4, 131.2,
130.3, 129.5, 128.3, 127.4, 126.1, 77.3, 66.6, 46.1, 38.9,
32.9, 23.2. LC-MS: m/z: (M + Na) 268. HR-MS calcd. for
C15H19NO2Na: 268.1313. Found: 268.1305.
i: N-(6-oxaspiro[4.5]dec-9-yl)acetamide
Light yellow solid, mp 112–114 °C. IR (KBr) ν: 3335,
2954, 2922, 2851, 1632, 1536, 1367, 1206, 1083, 821,
743 cm–1.1H NMR (200 MHz, CDCl3) δ: 1.24–1.75 (m,
12H), 1.87 (s, 3H), 3.45–3.71 (m, 2H), 3.91 (m, 1H), 5.81
(d, 1H, J = 8.0 Hz). 13C NMR (CDCl3, 75 MHz) δ: 23.1,
24.5, 33.1, 41.1, 42.1, 44.3, 61.0, 83.9, 169.2 ppm. LC-MS:
m/z (%): (M + H+) 198. HR-MS calcd. for C11H20NO2:
198.1494. Found: 198.1505.
e: N-[2-(1-naphthyl)tetrahydro-2H-4-pyranyl]acetamide
Pale yellow solid, mp 130–132 °C. IR (KBr) ν: 3294,
2956, 2926, 1648, 1553, 1366, 1087, 1042, 802, 730 cm–1.
1H NMR (300 MHz, CDCl3) δ: 1.42–1.67 (m, 2H), 1.97 (s,
3H), 2.04 (m, 1H), 2.42 (m, 1H), 3.84 (dt, 1H, J = 2.2,
12.0 Hz), 4.24–4.38 (m, 2H), 5.12 (dd, 1H, J = 1.7,
11.3 Hz), 5.27 (d, 1H, J = 7.5 Hz), 7.42 (m, 3H), 7.79 (m,
4H). 13C NMR (75 MHz, CDCl3) δ: 169.4, 137.4, 133.7,
130.2, 128.8, 128.1, 126.1, 125.5, 125.4, 123.1, 122.9, 75.9,
67.2, 46.6, 39.7, 33.0, 23.4. LC-MS: m/z: (M + Na) 292.
HR-MS calcd. for C17H19NO2Na: 292.1313. Found:
292.1320.
j: N-[1-oxaspiro[5.5]undec-4-yl]acetamide
Colourless solid, mp 148–150 °C. IR (KBr) ν: 3350,
2954, 2922, 2851, 1632, 1536, 1367, 1206, 1083, 821,
1
743 cm–1. H NMR (300 MHz, CDCl3) δ: 1.20–1.71 (m,
12H), 1.85 (dq, 1H J = 4.6, 12.0 Hz), 1.93 (s, 3H), 2.04
(ddq, 1H, J = 12.0, 4.4, 2.2 Hz), 3.63 (dt, 1H, J = 2.2,
12.0 Hz), 3.68 (m, 1H), 4.11 (m, 1H), 5.10 (d, 1H, J =
6.7 Hz). 13C NMR (75 MHz, CDCl3) δ: 169.3, 138.4, 137.2,
129.0, 125.6, 78.5, 66.9, 46.4, 40.6, 32.8, 23.4, 21.0. LC-
MS: m/z (%): (M
+ Na) 234. HR-MS calcd. for
C12H21NO2Na: 234.1469. Found: 234.1476.
f: N-[2-(3,4-dichlorophenyl)tetrahydro-2H-4-
pyranyl]acetamide
Pale yellow solid. mp 110–112 °C. IR (KBr) ν: 3316,
2945, 2852, 1643, 1543, 1376, 1077, 942, 812, 735 cm–1. 1H
NMR (300 MHz, CDCl3) δ: 1.23–1.55 (m, 2H), 1.95 (m,
1H), 1.99 (s, 3H), 2.22 (m, 1H), 3.67 (dt, 1H, J = 2.2,
12.0 Hz), 4.07–4.23 (m, 2H), 4.38 (dd, 1H, J = 1.7,
11.3 Hz), 5.34 (d, 1H, J = 7.5 Hz), 7.24 (m, 3H). 13C NMR
(75 MHz, CDCl3) δ: 169.8, 131.7, 131.2, 130.4, 130.2,
127.7, 124.9, 77.0, 66.8, 46.2, 40.4, 32.3, 23.2. LC-MS: m/z:
(M + Na) 311. HR-MS calcd. for C13H15Cl2NO2Na:
310.0377. Found: 310.0380.
k: N-[9-phenyl-1-oxaspiro[5.5]undec-4-yl]acetamide
Colourless solid, mp 172–174 °C. IR (KBr) ν: 3434,
3320, 2926, 2860, 1645, 1543, 1446, 1375, 1078, 971, 759,
1
701 cm–1. H NMR (200 MHz, CDCl3) δ: 1.13–1.38 (m,
3H), 1.32–1.77 (m, 6H), 1.84–1.98 (m, 5H), 2.39–2.55 (m,
2H), 3.64 (dt, 1H, J = 2.2, 12.0 Hz), 3.77 (ddd, 1H, J = 1.5,
5.2, 12.0 Hz), 4.15 (m, 1H), 5.58 (d, 1H, J = 7.5 Hz), 7.08–
7.25 (m, 5H). 13C NMR (75 MHz, CDCl3) δ: 169.3, 146.9,
128.1, 126.7, 125.7, 71.8, 59.3, 43.9, 43.5, 42.4, 39.8, 33.0,
29.4, 28.6, 28.0, 23.3. LC-MS: m/z (%): (M + Na) 310. HR-
MS calcd. for C18H25NO2Na: 310.1782. Found: 310.1788.
g: N-[2-(3,4,5-trimethoxyphenyl)tetrahydro-2H-4-
pyranyl]acetamide
l: N-(2-ethyltetrahydro-2H-4-pyranyl)-2-
phenylacetamide
Yellow solid, mp 210–212 °C. IR (KBr) ν: 3296, 2944,
2936, 1648, 1548, 1376, 1078, 1042, 814, 720 cm–1. 1H
NMR (300 MHz, CDCl3) δ: 1.32 (q, 1H, J = 12.4 Hz), 1.38
(dq, 1H, J = 4.5, 12.4 Hz), 1.93 (s, 3H), 2.06 (ddq, 1H, J =
12.6, 4.5, 2.2 Hz), 2.12 (ddt, 1H, J = 12.6, 4.5, 2.2 Hz), 3.63
(dt, 1H, J = 2.4, 12.2 Hz), 3.77 (s, 9H), 4.06 (m, 1H), 4.11
(m, 1H), 4.32 (dd, 1H, J = 2.0, 11.3 Hz), 5.30 (d, 1H, J =
7.5 Hz), 7.15–7.26 (m, 2H). 13C NMR (75 MHz, CDCl3) δ:
169.2, 153.0, 137.4, 137.1, 102.7, 78.3, 68.1, 66.2, 60.7,
55.9, 42.9, 35.2, 23.2. LC-MS: m/z: (M + Na) 332. HR-MS
calcd. for C16H23NO5Na: 332.1473. Found: 332.1484.
Light yellow solid, mp 90–92 °C. IR (KBr) ν: 3434, 3320,
2926, 2860, 1645, 1543, 1446, 1375, 1078, 971, 759,
1
701 cm–1. H NMR (200 MHz, CDCl3) δ: 1.13–1.38 (m,
3H), 1.32–1.77 (m, 6H), 1.84–1.98 (m, 5H), 2.39–2.55 (m,
2H), 3.64 (dt, 1H, J = 2.2, 12.0 Hz), 3.77 (ddd, 1H, J = 1.5,
5.2, 12.0 Hz), 4.15 (m, 1H), 5.58 (d, 1H, J = 7.5 Hz), 7.08–
7.25 (m, 5H). 13C NMR (75 MHz, CDCl3) δ: 179.6, 134.6,
130.8, 128.2, 127.0, 76.5, 66.4, 46.1, 38.1, 32.9, 28.9, 23.3,
9.6. LC-MS: m/z (%): (M + Na) 270. HR-MS calcd. for
C18H25NO2Na: 270.1469. Found: 270.1478.
h: N-[2-(3-nitrophenyl)tetrahydro-2H-4-
pyranyl]acetamide
m: N-(2-cyclohexyltetrahydro-2H-4-pyranyl)-2,2-
dimethylpropanamide
Yellow solid, mp 188–190 °C. IR (KBr) ν: 3308, 2956,
2926, 1648, 1625, 1515,1456, 1102, 1032, 812, 726 cm–1.
1H NMR (300 MHz, CDCl3) δ: 1.22 (q, 1H, J = 12.3 Hz),
1.44 (dq, 1H, J = 4.4, 12.3 Hz), 1.95 (s, 3H), 2.20 (ddq, 1H,
J = 12.3, 4.5, 2.4 Hz), 2.26 (ddt, 1H, J = 12.3, 4.5, 2.3 Hz),
3.67 (dt, 1H, J = 1.8, 12.0 Hz), 4.12 (m, 1H), 4.20 (m, 1H),
Colourless solid, mp 136–138 °C. IR (KBr) ν: 3434,
3320, 2926, 2860, 1645, 1543, 1446, 1375, 1078, 971, 759,
1
701 cm–1. H NMR (300 MHz, CDCl3) δ: 1.13–1.38 (m,
3H), 1.32–1.77 (m, 6H), 1.84–1.98 (m, 5H), 2.39–2.55 (m,
2H), 3.64 (dt, 1H, J = 2.2, 12.0 Hz), 3.77 (ddd, 1H, J = 1.5,
5.2, 12.0 Hz), 4.15 (m, 1H), 5.58 (d, 1H, J = 7.5 Hz), 7.08–
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Yadav et al.
773
7.25 (m, 5H). 13C NMR (75 MHz, CDCl3) δ: 177.7, 80.9,
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66.6, 46.2, 35.5, 33.1, 28.8, 27.4, 26.4, 26.1, 26.0, 25.3. LC-
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+ Na) 290. HR-MS calcd. for
2. K.C. Nicolaou and E.J. Sorensen. Classics in total synthesis.
VCH. Weinheim, Germany. 1996.
C18H25NO2Na: 290.2095. Found: 290.2089.
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n: 2-cyclohexyl-4-phenylcarboxamidotetrahydro-2H-
pyran
Pale brown solid, mp 112–114 °C. IR (KBr) ν: 3434,
3320, 2926, 2860, 1645, 1543, 1446, 1375, 1078, 971, 759,
1
701 cm–1. H NMR (200 MHz, CDCl3) δ: 1.13–1.38 (m,
3H), 1.32–1.77 (m, 6H), 1.84–1.98 (m, 5H), 2.39–2.55 (m,
2H), 3.64 (dt, 1H, J = 2.2, 12.0 Hz), 3.77 (ddd, 1H, J = 1.5,
5.2, 12.0 Hz), 4.15 (m, 1H), 5.58 (d, 1H, J = 7.5 Hz), 7.08–
7.25 (m, 5H). 13C NMR (75 MHz, CDCl3) δ: 166.8, 134.4,
131.4, 128.4, 126.8, 80.9, 68.5, 46.8, 35.7, 35.4, 28.8, 26.1,
26.0, 25.2. LC-MS: m/z (%): (M + Na) 310. HR-MS calcd.
for C18H25NO2Na: 310.1782. Found: 310.1786.
o: N-[2-(4-bromophenyl)-6-cyclohexyltetrahydro-2H-4-
pyranyl]acetamide
Pale yellow solid, mp 186–188 °C. IR (KBr) ν: 3278,
2923, 2848, 1643, 1553, 1488, 1369, 1154, 1085, 1010,
1
812 cm–1. H NMR (300 MHz, CDCl3) δ: 0.95–1.32 (m,
5H), 1.12 (m, 1H), 1.24 (m, 1H), 1.49 (m, 1H), 1.63– 1.85
(m, 5H), 1.94 (s, 3H), 2.00 (ddt, 1H, J = 2.0, 4.2, 2.0 Hz),
2.16 (ddt, 1H, J = 12.0, 4.2, 2.0 Hz), 3.30 (ddd, 1H, J =
11.0, 6.2, 2.0 Hz), 4.11 (ddt, 1H, J = 4.4, 8.5, 12.0 Hz), 4.35
(dd, 1H, J = 1.4, 11.0 Hz), 5.23 (d, 1H, J = 7.3 Hz), 7.18 (d,
2H, J = 8.5 Hz), 7.41 (d, 2H, J = 8.5 Hz). 13C NMR (CDCl3,
75 MHz) δ: 23.4, 26.2, 26.5, 28.7, 34.8, 40.4, 42.8, 46.7,
77.5, 80.7, 121.0, 127.3, 131.3, 141.6, 169.4 ppm. LC-MS:
m/z (%): (M + H+) 381. HR-MS calcd. for C19H27BrNO2:
380.1225. Found: 380.1234
6. M. Reiter, H. Turner, and V. Gouverneur. Chem. Eur. J. 27,
7190 (2006).
7. (a) E.H. Al-Mutairi, S.R. Crosby, J. Darzi, J.R. Harding, R.A.
Hughes, C.D. King, T.J. Simpson, R.W. Smith, and C.L. Wil-
lis. Chem. Commun. 835 (2001); (b) F. Perron and K.F.
Albizati. J. Org. Chem. 52, 4128 (1987); (c) O.L. Epstein, and
T. Rovis. J. Am. Chem. Soc. 128, 16480 (2006); (d) J.S.
Yadav, B.V. Subba Reddy, G.G.K.S. Narayana Kumar, and
M.G. Reddy. Tetrahedron Lett. 48, 4903 (2007).
8. (a) J.S. Yadav, M.S. Reddy, P.P. Rao, and A.R. Prasad. Tetra-
hedron Lett. 47, 4397 (2006); (b) J.S. Yadav, M.S. Reddy, and
A.R. Prasad. Tetrahedron Lett. 47, 4937 (2006); (c) J.S. Yadav,
M.S. Reddy, and A.R. Prasad. Tetrahedron Lett. 47, 4995
(2006); (d) J.S. Yadav, B.V. Subba Reddy, G.G.K.S. Narayana
Kumar, and T. Swamy. Tetrahedron Lett. 48, 2205 (2007);
(e) J.S. Yadav, B.V. Subba Reddy, S. Aravind, G.G.K.S.
Narayana Kumar, C. Madhavi, and A.C. Kunwar. Tetrahedron,
64, 3025 (2008).
p: N-(2-pentyl-6-phenyltetrahydro-2H-4-
pyranyl)acetamide
Pale yellow solid, mp 164–166 °C. IR (KBr) ν: 3434,
3320, 2926, 2860, 1645, 1543, 1446, 1375, 1078, 971, 759,
1
701 cm–1. H NMR (300 MHz, CDCl3) δ: 0.89 (t, 3H, J =
7.0 Hz), 0.98–1.64 (m, 10H), 1.94 (s, 3H), 2.02 (m, 1H),
2.19 (m, 1H), 3.53 (dt, 1H, J = 2.2, 12.0 Hz), 4.11 (m, 1H),
4.40 (m, 1H), 5.35 (d, 1H, J = 7.5 Hz), 7.14–7.33 (m, 5H).
LC-MS: m/z (%): (M + Na) 312. HR-MS calcd. for
C18H27NO2Na: 312.1939. Found: 312.1944.
9. (a) T. Imamoto. Lanthanides in organic synthesis. Academic
Press. London, UK. 1994. (b) G.A. Molander. Chem. Rev. 92,
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Synth. Org. Chem. Jpn. 53, 370 (1995); (c) S. Kobayashi. Eur.
J. Org. Chem. 15 (1999).
Acknowledgements
11. M.N. Leonard, L.C. Wieland, and R.S. Mohan. Tetrahedron
DNC, GGKSNK thank CSIR, New Delhi for the award of
fellowships and also thank DST for the financial assistance
under J.C. Bose fellowship scheme.
58, 8373 (2002).
12. S. Repichet, A. Zwick, L. Vendier, C. Le Roux, J. Dubac. Tet-
rahedron Lett. 43, 993 (2002).
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© 2008 NRC Canada