Suzuki reaction of vinyl triflates from six- and seven-membered N-alkoxycarbonyl lactams with boronic acids and esters

Article abstract of DOI:10.1021/jo001807c

The Pd(0)-catalyzed reaction of vinyl triflates from N-alkoxycarbonyl lactams with different boron compounds has been studied. The coupling reaction of alkenylboronates and arylboronic acids with six- and seven-membered lactam-derived N-alkoxycarbonyl vin

Full text of DOI:10.1021/jo001807c

J . Org. Chem. 2001, 66, 2459-2465
2459
Su zu k i Rea ction of Vin yl Tr ifla tes fr om Six- a n d Seven -Mem ber ed
N-Alk oxyca r bon yl La cta m s w ith Bor on ic Acid s a n d Ester s
Ernesto G. Occhiato,* Andrea Trabocchi, and Antonio Guarna
Dipartimento di Chimica Organica “U. Schiff” and Centro di Studio sulla Chimica e la Struttura dei
Composti Eterociclici e loro Applicazioni, CNR, Universita` di Firenze, Via G. Capponi 9,
I-50121 Firenze, Italy
occhiato@chimorg.unifi.it
Received December 30, 2000
The Pd(0)-catalyzed reaction of vinyl triflates from N-alkoxycarbonyl lactams with different boron
compounds has been studied. The coupling reaction of alkenylboronates and arylboronic acids with
six- and seven-membered lactam-derived N-alkoxycarbonyl vinyl triflates was feasible under very
mild conditions in THF-water employing (Ph3P)2PdCl2 as a catalyst and Na2CO3 as a base, which
provided in high yields the corresponding 6- or 7-substituted N-alkoxycarbonyl-3,4-dihydro-2H-
pyridines and N-alkoxycarbonyl-2,3,4,5-tetrahydroazepines. Allylboronates reacted slower but, with
vinyl triflates from δ-valerolactam, still gave acceptable yields of the coupling product. Alkylboronic
acids required different reaction conditions, in particular the presence of Ag2O together with a
base in anhydrous toluene and (dppf)PdCl2 as a catalyst, affording the corresponding 6-alkyl-N-
alkoxycarbonyl-3,4-dihydro-2H-pyridines in high yields.
Sch em e 1
In tr od u ction
In recent years there has been a growing interest in
the chemistry of lactam-derived vinyl triflates. It has
been shown that these compounds can undergo pal-
ladium-mediated displacement of the triflate group with
nucleophiles such as organotin and organozinc deriva-
tives, as well as methoxycarbonylation reactions.1 Cou-
pling reactions with organocuprates and organotin
compounds2-4 and Sonogashira-type cross-coupling reac-
tions with monosubstituted acetylenes5-7 have been
described by some authors, too. Most of these reactions
have been carried out on vinyl triflates from six-
membered lactams (Scheme 1) and on pyrrolidin-2-one-
derived triflates. These methodologies have been ex-
ploited in the synthesis of naturally occurring compounds
such as pipecolic acid,2 clavepictines A and B,6 desoxo-
prosophylline,8 and lepadin B.9
of lactam-derived vinyl triflates have been yet reported,
apart from our recent communication in which we
described the reaction of a small number of boron
derivatives with a δ-valerolactam-derived vinyl triflate.11
The possibility of forming new C-C bonds by Pd(0)-
catalyzed coupling of boronic acids or their esters with
vinyl triflates from N-alkoxycarbonyl lactams would
certainly extend the utility and scope of this reaction in
the preparation of heterocyclic compounds. Various meth-
odologies for the preparation of differently substituted
boronic acids and esters are indeed known,10a,12 and
moreover, a large number of them are now commercially
available. Moreover, unlike many organometallic deriva-
tives, boronic acids and their esters are usually stable to
Although the use of organoboron compounds as nu-
cleophiles in Pd-catalyzed cross-coupling reactions with
vinyl and aryl triflates is a powerful methodology in
organic synthesis,10 no examples of Suzuki-type reactions
* To whom correspondence should be addressed at Dipartimento di
Chimica Organica “Ugo Schiff”. Tel: 0039-055-2757611. Fax: 0039-
055-2476964.
(1) (a) Luker, T.; Hiemstra, H.; Speckamp, W. N. J . Org. Chem.
1997, 62, 8131-8140. (b) Luker, T.; Hiemstra, H.; Speckamp, W. N.
Tetrahedron Lett. 1996, 37, 8257-8260. (c) Bernabe´, P.; Rutjes, F. P.
J . T.; Hiemstra, H.; Speckamp, W. N. Tetrahedron Lett. 1996, 37,
3561-3564.
(2) Foti, C. J .; Comins, D. L. J . Org. Chem. 1995, 60, 2656-2657.
(3) Tsushima, K.; Hirade, T.; Hasegawa, H.; Murai, A. Chem. Lett.
1995, 9, 801-802.
(4) Beccalli, E. M.; Marchesini, A. Tetrahedron 1995, 51, 2353-2362.
(5) Okita, T.; Isobe, M. Tetrahedron 1995, 51, 3737-3744.
(6) Ha, J . D.; Lee, D.; Cha, J . K. J . Org. Chem. 1997, 62, 4550-
4551.
(7) Lindstro¨m, S.; Ripa, L.; Hallberg, A. Org. Lett. 2000, 2, 2291-
2293.
(8) Luker, T.; Hiemstra, H.; Speckamp, W. N. J . Org. Chem. 1997,
62, 3592-3596.
(9) Toyooka, N.; Okumura, M.; Takahata, H. J . Org. Chem. 1999,
64, 2182-2183.
(10) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457-2483.
(b) Oh-e, T.; Miyaura, N.; Suzuki, A. J . Org. Chem. 1993, 58, 2201-
2208.
(11) Occhiato, E. G.; Trabocchi, A.; Guarna, A. Org. Lett. 2000, 2,
1241-1242.
(12) (a) Brown, H. C.; Gupta, S. K. J . Am. Chem. Soc. 1975, 97,
5249-5255. (b) Miyaura, N.; Suzuki, A. Org. Synth. 1990, 68, 130-
136. (c) For the preparation of arylborinates and as an excellent source
of references for the preparation of boronic acids and esters, see:
Murata, M.; Oyama, T.; Watanabe, S.; Masuda, Y. J . Org. Chem. 2000,
65, 164-168.
10.1021/jo001807c CCC: $20.00 © 2001 American Chemical Society
Published on Web 03/14/2001

2460 J . Org. Chem., Vol. 66, No. 7, 2001
Occhiato et al.
Sch em e 2a
Sch em e 4
a
Key: (a) LiHMDS (1 M in THF), HMPA, PhNTf2, THF, -78
Ta ble 1. P d (0)-Ca ta lyzed Cr oss-Cou p lin g Rea ction of
Vin yl Tr ifla te 4 w ith Bor on a te 7
°C to rt, 16 h.
Sch em e 3
T
time yieldb
(°C) (h) (%)
entry
conditionsa
1
2
3
4
dioxane, K3PO4, 5% (Ph3P)4Pd
DMF, Cs2CO3, 5% (Ph3P)2PdCl2
DMF/2 M Cs2CO3 (aq) (4:1), 5% (Ph3P)2PdCl2
THF/2 M Na2CO3 (aq) (4:1), 5% (Ph3P)2PdCl2
85
40
40
5
4
4
c
c
72
82
82
20 16
40
40
80
6
2d 82d
2
81
16
c
45
27e
76
5
6
7
8
9
a
THF/2 M Na2CO3 (aq) (4:1), 5% (o-tol3P)2PdCl2 20 48
air and moisture and are of low toxicity and environ-
mental impact. In this paper, we thus wish to report on
the Pd(0)-catalyzed reaction of vinyl triflates from six-
and seven-membered N-alkoxycarbonyl lactams 4-6
(Schemes 2 and 3) with aryl-, alkenyl-, allyl-, and
alkylboronic acids or their esters and describe, for each
case, the best reaction conditions found for the new C-C
bond formation.13
THF/2 M Na2CO3 (aq) (4:1), 5% (dppe)PdCl2
THF/2 M Na2CO3 (aq) (4:1), 5% (dppf)PdCl2
THF/2 M NaOH (aq) (4:1), 5% Pd(dba)2
THF/2 M KF(aq), (3:1), 5% (Ph3P)2PdCl2
40
40
40
40
2
2
3
3
Reactions carried out with 1.5 equiv of 7 under nitrogen
atmosphere; reactions in entries 3-8 were carried out on about
0.3 mmol of 4 in 4 mL of organic solvent with 6.7 equiv of base;
the ratio between the volumes of the organic solvent and solution
b
of the base is reported in brackets. Yield of 8 after chromatog-
raphy. c Unreacted 4 was recovered in these cases. Experiment
d
carried out with distilled 7. e Conversion calculated by 1H NMR
Resu lts a n d Discu ssion
analysis of the crude reaction mixture.
Vinyl triflates 4-6 were prepared by treatment of
N-alkoxycarbonyl lactams 1-3 with LiHMDS and N-
phenyltriflimide, in the presence of HMPA at -78 °C and
then being left at room temperature for 16 h (Scheme
2), according to the method reported by Murai.3,14 N-Boc
and N-Cbz vinyl triflate 4 and 5 were obtained in 75%
and 92% yield, respectively, after chromatography. These
two compounds are stable at room or higher tempera-
tures and can be stored in the refrigerator for several
months. Seven-membered N-Cbz vinyl triflate 6 (obtained
in 65% yield), in our hands, was more prone to degrada-
tion, and during chromatographic purification it gave
back a considerable amount (about 25%) of its N-Cbz
caprolactam precursor 3. It was also less stable at room
temperature than compounds 4 and 5 and had to be
stored in the refrigerator to avoid a slow darkening of
the neat liquid.
In our study, we initially used N-Boc as the electron-
withdrawing protecting group. Since it is removable
under acid conditions, N-Boc can in fact provide possible
synthetic alternatives to other protecting groups such as
Cbz or Ts in the elaboration toward target heterocycles.
We also chose 2-[(E)-1-hexenyl]-1,3,2-benzodioxaborole
712a,b as the boron derivative counterpart, as in the
seminal work of Miyaura and Suzuki on the Pd(0)-
catalyzed reaction ofvinyltriflates with boron compounds.10b
The reaction of 4 with 7 (Scheme 4) to give 6-[(E)-1-
hexenyl]-3,4-dihydro-2H-piperidine derivative 8 was first
attempted under the conditions reported by these au-
thors, i.e., using (Ph3P)4Pd catalyst in dioxane at 85 °C
and K3PO4 as a base (Table 1, entry 1). However the
reaction did not occur at all, and we recovered after 5 h
the unreacted starting material 4. Also by carrying out
the reaction in anhydrous DMF, with Cs2CO3 as a base,
and 5% (Ph3P)2PdCl2 as a catalyst (entry 2), we were
unable to obtain the coupling product. Instead, the
addition of an aqueous base as 2 M Cs2CO3 (about 7
equiv) (entry 3) allowed the reaction to occur, affording
8 in 72% yield after 4 h at 40 °C with maintenance of
the double-bond geometry. Yields were improved using
THF as a solvent: when we used (Ph3P)2PdCl2 as a
catalyst (5% mol) in a THF-water mixture and in the
presence of an excess of Na2CO3 (about 7 equiv) as a base
(entry 4) the reaction proceeded quite fast at 40 °C,
affording 8 after 6 h in 82% yield; the reaction was
slightly slower at 20 °C and it reached completion (82%
yield) after 16 h, while at 80 °C proceeded fast and was
complete (yield 81%) after 2 h. In the above experiments,
we used crude 2-[(E)-1-hexenyl]-1,3,2-benzodioxaborole
7 obtained from the reaction of 1-hexyne and catecholbo-
rane for carrying out the reactions.12b However, when we
employed distilled 7, the reaction was much faster and
it reached completion after 2 h at 40 °C under the
conditions of entry 4.
We also tested (o-tol3P)2PdCl2 and (dppe)PdCl2 as
catalysts for the reaction of 4 with 7. In the first case,
the reaction was slower, furnishing 8 in 16% yield after
chromatography (the conversion was 35%) after 48 h at
room temperature (entry 5). With (dppe)PdCl2 we recov-
ered the unreacted starting material. Better results were
obtained by using 5% (dppf)PdCl2 (entry 7), which gave
8 in 45% yield after 2 h at 40 °C (the conversion was
65%). With Pd(dba)2 as a catalyst and 2 M NaOH as a
base (entry 8), without phosphine ligands, the conversion
was very low after 3 h at 40 °C (27%) (some Pd black
precipitated).
(13) We did not extend this study to N-alkoxycarbonylpyrrolidin-
2-one-derived vinyl triflates since they are highly unstable and of
difficult isolation due to rapid decomposition. The corresponding
N-tosyl-protected compounds are moderately stable only if an alkoxy
group is at the R-position to the nitrogen atom (see refs 1a,b and 2).
(14) Comins’ reagent N-(5-chloro-2-pyridyl)triflimide gives also
excellent yields in the preparation of vinyl triflates from lactams (see
refs 1a and 2).

Suzuki Reaction of Vinyl Triflates
J . Org. Chem., Vol. 66, No. 7, 2001 2461
Ta ble 2. P d (0)-Ca ta lyzed Cr oss-Cou p lin g Rea ction of Vin yl Tr ifla te 4 w ith Bor on Der iva tives 9-16a
a
Conditions: THF/2 M Na2CO3 (aq) v/v ratio 4:1 (entries 1-3) or 2:1 (entries 4-8), 5% (Ph3P)2PdCl2, 40 °C, 1.5 equiv of boron compound,
b
under nitrogen atmosphere. Yield of product after chromatography, with the exception of entry 2 (yield of the crude reaction mixture).
c Conversion calculated by 1H NMR analysis of the crude reaction mixture.
Sch em e 5
The presence of water seems necessary for the reaction
to occur. With the aqueous base the trans-metalation
process could be accelerated by the OH- ions that, by
quaternization of the boron atom, render the alkenyl
group more nucleophilic.10a Accordingly, also using 2 M
aqueous KF (entry 9), the conversion to product 8 was
complete in 3 h at 40 °C (76% yield). In this case, the
fluoride ion could have the same role of hydroxide anion
in the quaternization of the B atom.15 The weak basicity
and poor nucleophilicity of the fluoride ion could make
its use particularly useful in the case of base-sensitive
substrate.
with 4 (entry 3) was complete after 3 h at 40 °C, affording
6-phenyl-substituted N-Boc-3,4-dihydro-2H-pyridine 19
in 85% yield. The same compound was obtained in 87%
yield after 2 h at 40 °C using phenylboronic acid 12 (entry
4). In this case, we increased the volume of the aqueous
2 M Na2CO3. All the other boronic acids reacted smoothly
with 4 under these conditions, affording coupling prod-
ucts in high yields (entries 5, 6, and 8). The only exception
was the electron-poor 3-formylfuran-2-boronic acid 15,
which reacted slowly, furnishing coupling product 22
with a conversion of 50% after 6 h.16
The best conditions found in the first set of experiments
(Table 1, entry 4) are of general use for alkenylboronates
obtained from catecholborane and the corresponding
alkynes, as compounds 9-1012a-b (Table 2, entries 1 and
2). The reactions, carried out in THF with (Ph3P)2PdCl2
and Na2CO3 (aq) as a base, were successful in providing
the corresponding products 17 and 18 in 76 and 77%
yield, respectively (after 6 h at 40 °C the conversion was
complete in both cases). Compounds 17 and 18 both
maintained the geometry of the double bond.
The introduction of an aryl or heteroaryl group was
possible with the same methodology by using arylboronic
acids or their esters, such as the commercially available
compounds 11-16 (Table 2). The reaction of borinane 11
Alkenyl and aryl derivatives 8 and 17-23 (also as
N-Cbz derivatives) are stable under basic or neutral
conditions, but they are quite acid sensitive in the
(16) 1H NMR data of 22 (from the crude reaction mixture): δ 9.96
(s, 1 H), 7.30 (d, J ) 2.2 Hz, 1 H), 6.77 (d, J ) 2.2 Hz, 1 H), 5.59 (t, J
) 3.9 Hz, 1 H), 3.70 (m, 2 H), 2.34 (m, 2 H), 1.91 (m, 2 H), 1.20 (s, 9
H).
(15) Wright, S. W.; Hageman, D. L.; McClure, L. D. J . Org. Chem.
1994, 59, 6095-6097.

2462 J . Org. Chem., Vol. 66, No. 7, 2001
Occhiato et al.
Ta ble 3. P d (0)-Ca ta lyzed Cr oss-Cou p lin g Rea ction of Vin yl Tr ifla te 4 w ith Bor on Der iva tives 24-27
a
Method A: THF/2 M Na2CO3 (aq) v/v ratio 4:1 (entries 1-2) or 2:1 (entry 3), 5% (Ph3P)2PdCl2, 1.5 equiv of boron compound, under
nitrogen atmosphere. Method B: toluene, 3 equiv of K2CO3, 2 equiv of Ag2O, 3% (dppf)PdCl2, 2 equiv of boron compound, under nitrogen
atmosphere. Yield of product after chromatography. c The conversion was 66% after 3 h. Unreacted 4 was recovered in these cases.
b
d
presence of water. They can undergo ring opening to give
the corresponding open-chain unsaturated ketones
(Scheme 5). Compound 17 was the most acid sensitive
and even when left in CDCl3 (not stored over K2CO3)
underwent ring opening to give 38 in a 6:1 ratio with 17
after 48 h. Therefore, the chromatographic purification
of these compounds must be performed using 1‰ Et3N
in the eluant to avoid ring opening.17 This acid sensitivity
is instead lacking in the 6-alkyl and 6-allyl derivatives
(see later), since the equilibrium in these cases favors
the cyclic compounds.
As expected, alkylboronic acids were worse nucleo-
philes than alkenyl- and arylboronic acids in the reaction
with 4. The difficulties in Suzuki coupling reactions with
these compounds are known.18 In fact, the conditions
found for the reaction of the latter classes of boron
derivatives with 4 failed to give coupling products when
we used alkylboronates or alkylboronic acids (Table 3
entry 2-3) such as 25-26.19 Allylboron pinacolate 24
instead reacted with 4, but the yield of coupling product
28 was only 45% after 3 h at 80 °C. When we carried out
the reaction at 40 °C, we recovered the unreacted starting
material 4 even after 24 h. Prolonging the reaction time
at 80 °C did not considerably improve the conversion,
probably due to decomposition of the catalyst.
chlorides, using 3% (dppf)PdCl2, K2CO3, and Ag2O in
anhydrous toluene.21 The reaction failed to give the
coupling product with n-propylboronate 27, while it was
successful with n-butylboronic acid 26: after 9 h at 80
°C the coupling product 29 was obtained in 88% yield
after chromatography. The formation of a very small
amount of N-Boc-3,4-dihydro-2H-pyridine (less than 8%),
derived from â-hydride elimination from the trans-
1
metalated complex, was observed in the H NMR spec-
trum of the crude reaction mixture.
The reaction of N-Cbz-protected vinyl triflate 5 with
one representative of each class of boron derivatives
employed in this work was performed under the best
conditions previously found in the reactions with 4 (Table
4). We found a slightly higher reactivity compared to the
corresponding N-Boc derivative although, again, with the
allylboronate 24 (entry 3) the conversion was not com-
plete after 3 h at 80 °C (75% versus 66% after 3 h with
N-Boc derivative 4). Also, with 26 the reaction occurred
only when performed at 80 °C (entry 4) as with N-Boc
vinyl triflate 4, affording 6-alkyl derivative 33 in 93%
yield (in this case â-H elimination occurred for less than
5%).
The same series of boron derivatives was used for the
reaction with ꢀ-caprolactam derived N-Cbz vinyl triflate
6 (Table 5). In all cases, decomposition of the starting
material to the corresponding lactam 3 occurred in some
extent during the reaction, although this was negligible
(about 15%) when the reaction was very fast as with
boron derivatives 7 and 12 (entries 1 and 2). In fact, with
7 and 12 the reaction was complete just after 15 min at
40 °C, affording compounds 34 and 35 in 56 and 57%
yield after chromatography. Unexpectedly, in the reaction
carried out under the same conditions and at 40 °C with
allylboronate 24 we recovered only N-Cbz lactam 3. The
low temperature was not sufficient to promote the
reaction, and thus decomposition occurred. Decomposi-
tion to lactam 3 was still the main pathway when the
reaction was carried out at 80 °C, but in this case we
Because Ag2O is reported to accelerate the trans-
metalation process,20 we tried the conditions reported by
Deng for the reaction of cyclopropylboronic acids with acyl
(17) Ring opening does not occur in the presence of acids under
anhydrous conditions. For example, reduction of the double bond in
related 6-alkynyl derivatives has been successfully carried out in
anhydrous TFA without ring opening (ref 6). Also, we were able to
remove the N-Boc protection from 19 by treatment with TMSOTf in
anhydrous CH2Cl2, thus obtaining the corresponding cyclic imine (6-
phenyl-2,3,4,5-tetrahydropyridine) in good yield.
(18) Molander, G. A.; Ito, T. Org. Lett. 2001, 3, 393-396 and
references therein.
(19) Compound 25 was prepared as reported (see ref 12a).
(20) (a) Uenishi, J .; Beau, J .-M.; Armstrong, R. W.; Kishi, Y. J . Am.
Chem. Soc. 1987, 109, 4756-4758. (b) Gillmann, T.; Weeber, T. Synlett
1994, 649-650. (c) Gronowitz, S.; Bjo¨rk, P.; Malm, J .; Ho¨rnfeldt, A.
B. J . Organomet. Chem. 1993, 460, 127-129.
(21) Chen, H.; Deng, M.-Z. Org. Lett. 2000, 2, 1649-1651.

Suzuki Reaction of Vinyl Triflates
J . Org. Chem., Vol. 66, No. 7, 2001 2463
Ta ble 4. P d (0)-Ca ta lyzed Cr oss-Cou p lin g Rea ction of Vin yl Tr ifla te 5 w ith Selected Bor on Der iva tives
a
Method A: THF/2 M Na2CO3 (aq) v/v ratio 4:1 (entries 1 and 3) or 2:1 (entry 2), 5% (Ph3P)2PdCl2, 1.5 equiv of boron compound, under
nitrogen atmosphere. Method B: toluene, 3 equiv of K2CO3, 2 equiv of Ag2O, 3% (dppf)PdCl2, 2 equiv of boron compound, under nitrogen
b
atmosphere. Yield of product after chromatography with the exception of entry 2 (yield of the crude reaction mixture). c The conversion
was 75% after 3 h.
Ta ble 5. P d (0)-Ca ta lyzed Cr oss-Cou p lin g Rea ction of Vin yl Tr ifla te 6 w ith Selected Bor on Der iva tives
a
Method A: THF/2 M Na2CO3 (aq) v/v ratio 4:1 (entries 1 and 3) or 2:1 (entry 2), 5% (Ph3P)2PdCl2, 1.5 equiv of boron compound, under
nitrogen atmosphere. Method B: toluene, 3 equiv of K2CO3, 2 equiv of Ag2O, 3% (dppf)PdCl2, 2 equiv of boron compound, under nitrogen
b
atmosphere. Yield of product after chromatography. c Conversion calculated by 1H NMR analysis of the crude reaction mixture.
observed a 27% conversion to 36.22 Analogously, the
reaction did not proceed well under Deng’s conditions
(method B) and we obtained, after 7 h at 80 °C, again
mainly decomposition to 3 and coupling product 37 in
22% yield after chromatography. From these results, it
appears that the triflates from a seven-membered ring,
although more reactive, are more susceptible to decom-
position when the reaction is slow23 and only those boron
reagents that react quickly with 6 appear useful for the
C-C bond formation.
groups on piperidine and azepine rings by coupling with
the corresponding N-alkoxycarbonyl vinyl triflates. The
coupling reaction of alkenylboronates and arylboronic
acids with six- and seven-membered lactam-derived
N-alkoxycarbonyl vinyl triflates is feasible under very
mild conditions in THF-water, employing (Ph3P)2PdCl2
as a catalyst, which provides in high yields the corre-
sponding 6- or 7-substituted N-alkoxycarbonyl-3,4-dihy-
dro-2H-pyridines and N-alkoxycarbonyl-2,3,4,5-tetrahy-
droazepines. Allylboronates react slower under those
conditions but, with vinyl triflates from δ-valerolactam,
still give acceptable yields of the coupling product.
Alkylboronic acids require different reaction conditions,
in particular the presence of Ag2O together with a base
in anhydrous toluene and (dppf)PdCl2 as catalyst. Under
these conditions, vinyl triflates 4 and 5 react smoothly
to give the corresponding 6-alkyl-3,4-dihydro-2H-pip-
eridines in high yields. The application of this methodol-
ogy to the synthesis of heterocyclic compounds is cur-
rently investigated in our laboratory.
Con clu sion
In conclusion, we have shown that the Suzuki reaction
is suitable for introducing aryl, alkenyl, allyl, and alkyl
(22) 1H NMR data of 36 (from the crude reaction mixture): δ 7.42-
7.27 (m, 5 H), 5.85-5.60 (m, 1 H), 5.43 (t, J ) 5.5 Hz, 1 H), 5.14 (s, 2
H), 5.00-4.85 (m, 2 H), 3.56 (m, 2 H), 2.92 (d, J ) 7.3 Hz, 2 H), 2.23
(m, 2 H), 2.13 (m, 2 H), 1.57-1.44 (m, 4 H).
(23) If the trans-metalation process is slow, either the high tem-
perature or the presence of water cause progressive degradation of the
starting material during the course of the reaction.

2464 J . Org. Chem., Vol. 66, No. 7, 2001
Occhiato et al.
mmol), but heating at 40 °C for 6 h. Pure 17 (52 mg, 76%)
was obtained after purification by chromatography (CH2Cl2-
petroleum ether 1:2, Et3N 1‰, Rf 0.14) as a colorless oil: 1H
NMR (CDCl3) δ 7.40-7.13 (m, 5 H), 6.55 (AB system, J ) 16
Hz, 2 H), 5.43 (t, J ) 3.8 Hz, 1 H), 3.57 (m, 2 H), 2.22 (m, 2
H), 1.79 (m, 2 H), 1.37 (s, 9 H); 13C NMR (CDCl3) δ 138.5 (s),
137.4 (s), 128.5 (d, 2 C), 127.9 (s), 127.7 (d), 127.1 (d), 126.3
(d), 126.2 (d, 2 C), 115.7 (d), 80.5 (s), 44.4 (t), 28.3 (q, 3 C),
23.7 (t), 23.4 (t); MS m/z 285 (M+, 1), 186 (26), 103 (40), 57
(100). Anal. Calcd for C18H23NO2: C, 75.76; H, 8.12; N, 4.91.
Found: C, 75.61; H, 8.46; N, 4.77.
Exp er im en ta l Section
All solvents were degassed before use. Chromatographic
separations were performed under pressure on silica gel using
flash-column techniques; Rf values refer to TLC carried out
on 25-mm silica gel plates (Merck F254), with the same eluant
indicated for the column chromatography. 1H and 13C NMR
spectra were recorded at 200 and 50.33 MHz, respectively.
Boron derivatives 11-16, 24, 26, and 27 are commercially
available.
6-Tr iflu or om eth a n esu lfon yloxy-3,4-d ih yd r o-2H-p yr i-
d in e-1-ca r boxylic Acid ter t-Bu tyl Ester (4). To a solution
of 1 (1.0 g, 5.02 mmol) in anhydrous THF (30 mL), cooled to
-78 °C, was added a 1 M solution of LiHMDS in THF (6.25
mL, 6.25 mmol) over 35 min, and the mixture was stirred for
70 min. Distilled HMPA (1.75 mL, 10.04 mmol) was added,
the solution was stirred for an additional 15 min, and then a
solution of PhNTf2 (2.23 g, 6.25 mmol) in anhydrous THF (5
mL) was added and the mixture allowed to warm to room
temperature and left to react for 15 h. Water (50 mL) was
added, and the organic products were extracted with diethyl
ether (3 × 40 mL), washed with 10% aqueous NaOH, and dried
over anhydrous K2CO3. The crude product was purified by
flash chromatography (CH2Cl2-petroleum ether 1:2, Rf 0.27)
affording compound 4 (1.24 g, 75%) as a pale yellow oil: 1H
NMR (CDCl3) δ 5.27 (t, J ) 4.0 Hz, 1 H), 3.58 (m, 2 H), 2.24
(m, 2 H), 1.74 (m, 2 H), 1.47 (s, 9 H).
6-Tr iflu or om eth a n esu lfon yloxy-3,4-d ih yd r o-2H-p yr i-
d in e-1-ca r boxylic Acid Ben zyl Ester (5). A solution of 2
(2.61 g, 11.2 mmol) in anhydrous THF (60 mL) was cooled to
-78 °C, a 1 M solution of LiHMDS in THF (14 mL, 14.0 mmol)
was added over 30 min, and the mixture was stirred for 70
min. Distilled HMPA (3.92 mL, 22.5 mmol) was added, the
solution was stirred for an additional 15 min, and then a
solution of PhNTf2 (5.0 g, 14.0 mmol) in anhydrous THF (12
mL) was added and the mixture allowed to warm to room
temperature and left to react for 15 h. Water (100 mL) was
added, and the organic products were extracted with diethyl
ether (3 × 60 mL), washed with 10% aqueous NaOH, and dried
over anhydrous K2CO3. The crude mixture was purified by
flash chromatography (EtOAc-petroleum ether 1:5, Rf 0.41)
yielding pure compound 4 (3.76 g, 92%) as a yellowish oil: 1H
NMR (CDCl3) δ 7.34 (m, 5 H), 5.32 (t, J ) 4.0 Hz, 1 H), 5.19
(s, 2 H), 3.66 (m, 2 H), 2.25 (m, 2 H), 1.76 (m, 2 H).
7-Tr iflu or om e t h a n e su lfon yloxy-2,3,4,5-t e t r a h yd r o-
a zep in e-1-ca r boxylic Acid Ben zyl Ester (6). Compound 6
was prepared according to the procedure reported for 5 starting
from 3 (2.2 g, 8.9 mmol). Pure 6 (2.19 g, 65%) was obtained as
a yellow oil after a rapid purification by chromatography on
silica gel using a more polar eluant (EtOAc-petroleum ether
1:2, Rf 0.76): 1H NMR (CDCl3) δ 7.33 (m, 5 H), 5.69 (t, J ) 7.0
Hz, 1 H), 5.19 (s, 2 H), 3.58 (m, 2 H), 2.13 (m, 2 H), 1.73 (m,
2 H), 1.55 (m, 2 H).
6-[(E)-(1-Eth yl-bu t-1-en yl)-3,4-d ih yd r o-2H-p yr id in e-1-
ca r boxylic Acid ter t-Bu tyl Ester (18). Compound 18 was
prepared as reported for 8 starting from 4 (52 mg, 0.16 mmol)
and 10 (48 mg, 0.24 mmol), but heating at 40 °C for 6 h.
Compound 18 (33 mg, 77%) was obtained after usual workup
as a sufficiently pure oil: 1H NMR (CDCl3) δ 5.37 (t, J ) 7.0
Hz, 1 H), 5.12 (t, J ) 3.7 Hz, 1 H), 3.51 (m, 2 H), 2.36-1.98
(m, 6 H), 1.76 (m, 2 H), 1.38 (s, 9 H), 0.96 (t, J ) 7.7 Hz, 3 H),
0.85 (t, J ) 7.3 Hz, 3 H); 13C NMR (CDCl3) δ 141.0 (s), 126.9
(s), 126.1 (d), 113.1 (d), 112.1 (s), 80.2 (s), 44.3 (t), 28.3 (q, 3
C), 23.8 (t), 23.4 (t), 21.4 (t), 21.0 (t), 14.3 (q), 13.3 (q); MS m/z
265 (M+, 0.5), 164 (70), 57 (100). Anal. Calcd for C16H27NO2:
C, 72.41; H, 10.25; N, 5.28. Found: C, 72.13; H, 10.03; N, 4.98.
6-P h en yl-3,4-d ih yd r o-2H-p yr id in e-1-ca r boxylic Acid
ter t-Bu tyl Ester (19). To a solution of 4 (70 mg, 0.21 mmol)
in THF (4 mL) were added, under a nitrogen atmosphere,
(Ph3P)2PdCl2 (7.5 mg, 10.5 µmol), phenylboronic acid 12 (122
mg, 0.32 mmol), and a 2 M aqueous Na2CO3 solution (2 mL).
The mixture continued stirring for 2 h at 40 °C. Water (10
mL) was then added and the mixture extracted with diethyl
ether and dried over anhydrous sodium sulfate. Chromatog-
raphy (CH2Cl2-petroleum ether 1:2, Et3N 1‰, Rf 0.15) af-
forded 19 (47 mg, 87%) as an oil: 1H NMR (CDCl3) δ 7.26 (m,
5 H), 5.31 (t, J ) 3.7 Hz, 1 H), 3.71 (m, 2 H), 2.26 (dt, J ) 7.0,
3.7 Hz, 2 H), 1.87 (m, 2 H), 1.06 (s, 9 H); 13C NMR (CDCl3) δ
140.8 (s), 131.9 (s), 128.7 (s), 127.8 (d, 2 C), 126.7 (d), 125.2
(d, 2 C), 115.0 (d), 80.3 (s), 44.4 (t), 27.7 (q, 3 C), 23.7 (t), 23.6
(t); MS m/z 259 (M+, 10), 159 (51), 158 (86), 84 (83), 57 (83).
Anal. Calcd for C16H21NO2: C, 74.10; H, 8.16; N, 5.40. Found:
C, 73.92; H, 8.34; N, 5.09.
6-(3-Acet oxyp h en yl)-3,4-d ih yd r o-2H -p yr id in e-1-ca r -
boxylic Acid ter t-Bu tyl Ester (20). Compound 20 was
prepared according to the procedure reported for 19 starting
from 4 (103 mg, 0.31 mmol) and 13 (76 mg, 0.47 mmol). Pure
20 (86 mg, 88%) was obtained after chromatography (CH2Cl2-
petroleum ether 1:2, Et3N 1‰, Rf 0.4) as an oil: 1H NMR
(CDCl3) δ 7.80 (m, 2 H), 7.50-7.26 (m, 2 H), 5.35 (t, J ) 3.7
Hz, 1 H), 3.69 (m, 2 H), 2.55 (s, 3 H), 2.25 (m, 2 H), 1.84 (m,
2 H), 1.02 (s, 9 H); 13C NMR (CDCl3) δ 197.9 (s), 153.6 (s),
141.3 (s), 139.3 (s), 136.8 (s), 129.8 (d), 128.1 (d), 126.6 (d),
125.1 (d), 116.0 (d), 80.4 (s), 44.4 (t), 27.7 (q, 3 C), 26.6 (q),
23.7 (t), 23.4 (t); MS m/z 301 (M+-15, 1), 201 (40), 57 (100).
Anal. Calcd for C18H23NO4: C, 68.12; H, 7.30; N, 4.41. Found:
C, 68.00; H, 6.98; N, 4.33.
6-Fu r an -2-yl-3,4-dih ydr o-2H-pyr idin e-1-car boxylic Acid
ter t-Bu tyl Ester (21). Compound 21 was prepared according
to the procedure reported for 19 starting from 4 (50 mg, 0.15
mmol) and 14 (25 mg, 0.23 mmol). Pure 21 (35 mg, 94%) was
obtained after chromatography (CH2Cl2-petroleum ether 1:2,
Et3N 1‰, Rf 0.38) as an oil: 1H NMR (CDCl3) δ 7.31 (br s, 1
H), 6.33 (m, 1 H), 6.20 (d, J ) 3.3 Hz, 1 H), 5.50 (t, J ) 3.8 Hz,
1 H), 3.64 (m, 2 H), 2.24 (m, 2 H), 1.83 (m, 2 H), 1.24 (s, 9 H);
13C NMR (CDCl3) δ 152.8 (s), 141.6 (s), 140.2 (d), 131.4 (s),
114.3 (d), 110.8 (d), 104.7 (d), 80.4 (s), 44.1 (t), 27.8 (q, 3 C),
23.5 (t), 23.2 (t); MS m/z 249 (M+, 8), 183 (11), 149 (34), 84
(100). Anal. Calcd for C14H19NO3: C, 67.45; H, 7.68; N, 5.62.
Found: C, 67.32; H, 7.74; N, 5.42.
6-Th iop h en -2-yl-3,4-d ih yd r o-2H -p yr id in e-1-ca r b oxyl-
ic Acid ter t-Bu tyl Ester (23). Compound 23 was prepared
according to the procedure reported for 19 starting from 4 (50
mg, 0.15 mmol) and 16 (29 mg, 0.23 mmol). Pure 23 (36 mg,
91%) was obtained after chromatography (CH2Cl2-petroleum
ether 1:2, Et3N 1‰, Rf 0.43) as an oil: 1H NMR (CDCl3) δ 7.10
(dd, J ) 4.4, 2.2 Hz, 1 H), 6.92 (m, 2 H), 5.44 (t, J ) 3.8 Hz, 1
6-[(E)-H ex-1-en yl]-3,4-d ih yd r o-2H -p yr id in e-1-ca r b ox-
ylic Acid ter t-Bu tyl Ester (8). To a solution of 4 (93 mg, 0.28
mmol) in THF (4 mL) were added, under a nitrogen atmo-
sphere, (Ph3P)2PdCl2 (10 mg, 14 µmol), distilled 7 (85 mg, 0.42
mmol), and a 2 M aqueous Na2CO3 solution (1 mL). The
mixture continued stirring for 2 h at 40 °C. Water (10 mL)
was then added and the mixture extracted with diethyl ether
and dried over anhydrous sodium sulfate. Evaporation of the
solvent afforded a brown oil that was purified by chromatog-
raphy (CH2Cl2-petroleum ether 1:2, 1‰ Et3N, Rf 0.15) to give
8 (61 mg, 82%) as a colorless oil: 1H NMR (CDCl3) δ 5.85 (d,
J ) 15.6 Hz, 1 H), 5.67 (m, 1 H), 5.19 (t, J ) 3.8 Hz, 1 H), 3.50
(t, J ) 5.2 Hz, 2 H), 2.09 (m, 4 H), 1.75 (m, 2 H), 1.41 (s, 9 H),
1.29 (m, 4 H), 0.86 (t, J ) 6.6 Hz, 3 H); 13C NMR (CDCl3) δ
147.5 (s), 138.5 (s), 128.4 (d), 127.8 (d), 112.9 (d), 80.3 (s), 44.4
(t), 32.2 (t), 31.5 (t), 28.3 (q, 3 C), 23.5 (t), 23.4 (t), 22.4 (t),
14.0 (q); MS m/z 265 (M+, 0.2), 166 (8), 165 (2), 57 (100). Anal.
Calcd for C16H27NO2: C, 72.41; H, 10.25; N, 5.28. Found: C,
72.11; H, 10.43; N, 5.01.
6-[(E)-Styr yl]-3,4-dih ydr o-2H-pyr idin e-1-car boxylic Acid
ter t-Bu tyl Ester (17). Compound 17 was prepared as reported
for 8 starting from 4 (80 mg, 0.24 mmol) and 9 (80 mg, 0.36

Suzuki Reaction of Vinyl Triflates
J . Org. Chem., Vol. 66, No. 7, 2001 2465
H), 3.65 (m, 2 H), 2.24 (m, 2 H), 1.83 (m, 2 H), 1.19 (s, 9 H);
13C NMR (CDCl3) δ 144.5 (s), 134.3 (s), 131.9 (s), 126.5 (d),
122.9 (d), 122.3 (d), 115.2 (d), 80.6 (s), 44.6 (t), 27.8 (q, 3 C),
23.6 (t), 23.4 (t); MS m/z 265 (M+, 6), 165 (22), 84 (100). Anal.
Calcd for C14H19NO2S: C, 63.36; H, 7.22; N, 5.28. Found: C,
63.08; H, 7.44; N, 4.97.
6-Allyl-3,4-d ih yd r o-2H-p yr id in e-1-ca r boxylic Acid ter t-
Bu tyl Ester (28). Compound 28 was prepared as reported for
8 starting from 4 (106 mg, 0.32 mmol) and 24 (90 µL, 0.48
mmol) but heating at 80 °C for 3 h. Pure 28 (34 mg, 45%) was
obtained after purification by chromatography (CH2Cl2-MeOH
20:1, 1‰ Et3N, Rf 0.3): 1H NMR (CDCl3) δ 5.84-5.67 (m, 1
H), 5.03 (dd, J ) 9.9, 1.8 Hz, 1 H), 4.96 (m, 2 H), 3.50 (m, 2
H), 3.18 (dd, J ) 6.6, 1.5 Hz, 2 H), 2.04 (m, 2 H), 1.73 (m, 2
H), 1.41 (s, 9 H); 13C NMR (CDCl3): δ 152.2 (s), 140.1 (s), 136.0
(d), 115.8 (t), 112.6 (d), 80.4 (s), 44.9 (t), 39.5 (t), 28.4 (q, 3 C),
23.4 (t), 23.1 (t); MS m/z 122 (M+-101, 36), 57 (100). Anal. Calcd
for C13H21NO2: C, 69.92; H, 9.48; N, 6.27. Found: C, 70.04;
H, 9.22; N, 6.12.
2 H), 1.76 (m, 2 H); 13C NMR (CDCl3) δ 154.2 (s), 136.4 (s),
135.9 (d), 129.4 (s), 128.4 (d, 2 C), 128.0 (d, 3 C), 115.9 (t),
113.2 (d), 67.3 (t), 45.2 (t), 39.2 (t), 29.7 (t), 23.0 (t); MS m/z
257 (M+, 2), 91 (100). Anal. Calcd for C16H19NO2: C, 74.68; H,
7.44; N, 5.44. Found: C, 74.77; H, 7.22; N, 5.38.
6-Bu tyl-3,4-dih ydr o-2H-pyr idin e-1-car boxylic Acid Ben -
zyl Ester (33). Compound 33 was prepared as reported for
29 starting from 5 (180 mg, 0.49 mmol) and 26 (101 mg, 0.98
mmol), heating 8 h at 80 °C. Pure 33 (124 mg, 93%) was
obtained after chromatography (EtOAc-petroleum ether 1:4,
Rf 0.6): 1H NMR (CDCl3) δ 7.33 (m, 5 H), 5.13 (s, 2 H), 4.96 (t,
J ) 3.6 Hz, 1 H), 3.56 (m, 2 H), 2.44 (t, J ) 7.0 Hz, 2 H), 2.02
(m, 2 H), 1.75 (m, 2 H), 1.24 (m, 4 H), 0.82 (t, J ) 7.0 Hz, 3 H);
13C NMR (CDCl3) δ 154.1 (s), 139.8 (s), 136.3 (s), 128.3 (d, 2
C), 128.0 (d, 2 C), 127.9 (d), 112.4 (d), 67.2 (t), 45.1 (t), 34.7
(t), 29.9 (t), 23.4 (t), 22.8 (t), 22.2 (t), 13.9 (q); MS m/z 182 (M+
- 91, 2), 91 (100). Anal. Calcd for C17H23NO2: C, 74.69; H,
8.48; N, 5.12. Found: C, 74.45; H, 8.18; N, 5.01.
7-[(E)-Hex-1-en yl]-2,3,4,5-tetr a h yd r oa zep in e-1-ca r box-
ylic Acid Ben zyl Ester (34). Compound 34 was prepared as
reported for 8 starting from 6 (80 mg, 0.21 mmol) and 7 (63
mg, 0.32 mmol), but heating for 15 min at 40 °C. Pure 34 (37
mg, 56%) was obtained after purification by chromatography
(EtOAc-petroleum ether 1:4, 1‰ Et3N, Rf 0.75) as an oil: 1H
NMR (CDCl3) δ 7.34 (m, 5 H), 6.02-5.86 (m, 1 H), 5.72-5.41
(m, 1 H), 5.21-5.00 (m, 1 H), 5.15 (s, 2 H), 3.70 (m, 2 H), 2.02
(m, 2 H), 1.74 (m, 4 H), 1.34-1.15 (m, 6 H), 0.87 (t, J ) 6.6
Hz, 3 H); 13C NMR (CDCl3) δ 152.2 (s), 133.5 (s), 130.1 (s),
129.7 (d), 128.4 (d, 2 C), 127.7 (d, 2 C), 122.3 (d), 112.1 (d),
67.8 (t), 47.7 (t), 35.7 (t), 35.2 (t), 30.5 (t), 30.3 (t), 25.5 (t),
22.2 (t), 13.9 (q); MS m/z 313 (M+, 2), 178 (10), 91 (100). Anal.
Calcd for C20H27NO2: C, 76.64; H, 8.68; N, 4.47. Found: C,
76.51; H, 8.79; N, 4.48.
6-Bu tyl-3,4-dih ydr o-2H-pyr idin e-1-car boxylic Acid ter t-
Bu tyl Ester (29). To a solution of 4 (110 mg, 0.33 mmol) in
anhydrous toluene (2 mL) were added, under a nitrogen
atmosphere, (dppf)PdCl2 (7 mg, 9.9 µmol), 26 (67 mg, 0.66
mmol), Ag2O (152 mg, 0.66 mmol), and finely triturated K2-
CO3 (137 mg, 0.99 mmol). The mixture continued stirring for
9 h at 80 °C. Diethyl ether (10 mL) was then added, Ag2O
filtered out, and the filtrate washed with water and dried over
anhydrous sodium sulfate. After evaporation of the solvent,
the crude mixture was purified by chromatography (EtOAc-
petroleum ether 1:15, Rf 0.56) to give 29 (69 mg, 88%) as an
oil: 1H NMR (CDCl3) δ 4.92 (t, J ) 3.6 Hz, 1 H), 3.48 (m, 2 H),
2.44 (t, J ) 7.4 Hz, 2 H), 2.04 (m, 2 H), 1.78-1.70 (m, 2 H),
1.46 (s, 9 H), 1.37-1.19 (m, 4 H), 0.86 (t, J ) 7.0 Hz, 3 H); 13
C
NMR (CDCl3): δ 140.1 (s), 128.2 (s), 111.9 (d), 80.2 (s), 44.9
(t), 35.1 (t), 29.9 (t), 28.4 (q, 3 C), 23.6 (t), 23.1 (t), 22.3 (t),
14.1 (q); MS m/z 239 (M+, 6), 141 (60), 97 (100). Anal. Calcd
for C14H25NO2: C, 70.25; H, 10.53; N, 5.85. Found: C, 70.51;
H, 10.37; N, 5.72.
7-P h en yl-2,3,4,5-tetr a h yd r oa zep in e-1-ca r boxylic Acid
Ben zyl Ester (35). Compound 35 was prepared according to
the procedure reported for 19, starting from 6 (80 mg, 0.21
mmol) and 12 (38 mg, 0.32 mmol), but heating for 15 min at
40 °C. Pure 35 (37 mg, 57%) was obtained after chromatog-
raphy (EtOAc-petroleum ether 1:4, 1‰ Et3N, Rf 0.56) as a
6-[(E)-H ex-1-en yl]-3,4-d ih yd r o-2H -p yr id in e-1-ca r b ox-
ylic Acid Ben zyl Ester (30). Compound 30 was prepared as
reported for 8 starting from 5 (365 mg, 1.00 mmol) and 7 (303
mg, 1.50 mmol), but heating 1.5 h at 40 °C. Pure 30 (257 mg,
86%) was obtained after purification by chromatography
(EtOAc-petroleum ether 1:5, 1‰ Et3N, Rf 0.56) as an oil: 1H
NMR (CDCl3) δ 7.37-7.29 (m, 5 H), 5.90 (d, J ) 15.7 Hz, 1
H), 5.74-5.60 (m, 1 H), 5.27 (t, J ) 4.0 Hz, 1 H), 5.14 (s, 2 H),
3.60 (m, 2 H), 2.15 (m, 2 H), 2.02 (m, 2 H), 1.80 (m, 2 H), 1.28
(m, 4 H), 0.86 (m, 3 H); 13C NMR (CDCl3) δ 154.8 (s), 138.2
(s), 136.2 (s), 128.6 (d), 128.4 (d), 128.2 (d, 2 C), 127.8 (d, 2 C),
127.7 (d), 113.8 (d), 67.3 (t), 44.8 (t), 32.0 (t), 31.3 (t), 23.3 (t),
23.1 (t), 22.2 (t), 13.9 (q); MS m/z 299 (M+, 2), 91 (100). Anal.
Calcd for C19H25NO2: C, 76.22; H, 8.42; N, 4.68. Found: C,
76.04; H, 8.19; N, 4.51.
6-P h en yl-3,4-d ih yd r o-2H-p yr id in e-1-ca r boxylic Acid
Ben zyl Ester (31). Compound 31 was prepared according to
the procedure reported for 19, starting from 5 (180 mg, 0.50
mmol) and 12 (91 mg, 0.75 mmol). Compound 31 (123 mg, 84%)
was obtained after usual workup in sufficiently pure form as
an oil: 1H NMR (CDCl3) δ 7.29-7.18 (m, 8 H), 6.79 (m, 2 H),
5.43 (t, J ) 4.0 Hz, 1 H), 4.93 (s, 2 H), 3.79 (m, 2 H), 2.28 (m,
2 H), 1.89 (m, 2 H); 13C NMR (CDCl3) δ 154.9 (s), 139.8 (s),
132.0 (s), 131.8 (s), 128.0 (d, 2 C), 127.9 (d, 2 C), 127.5 (d),
127.4 (d, 2 C), 127.0 (d), 125.0 (d, 2 C), 116.3 (d), 67.4 (t), 45.1
(t), 23.5 (t, 2 C); MS m/z 293 (M+, 4), 91 (100). Anal. Calcd for
1
white solid: mp 82-83 °C; H NMR (CDCl3) (3:1 mixture of
rotamers) δ 7.60-7.25 (m, 6 H), 7.11 (m, 2 H), 6.68 (dd, J )
8.1, 2.2 Hz, 2 H), 6.03 (t, J ) 6.6 Hz, 1 H), 4.92 (br s, 1 H),
3.80-3.40 (br s, 2 H), 2.28 (m, 2 H), 1.86 (m, 2 H), 1.56 (m, 2
H) (major rotamer), 6.10 (t, J ) 6.6 Hz, 1 H) and 5.14 (s, 2 H)
(minor rotamer); 13C NMR (CDCl3) δ 143.6 (s), 138.4 (s), 128.6
(s), 128.3 (d, 2 C), 127.9 (d, 2 C), 127.4 (d), 127.3 (d), 127.1 (s),
127.0 (d, 2 C), 124.6 (d, 2 C), 123.9 (d), 66.9 (t), 48.5 (t), 29.7
(t), 27.3 (t), 24.1 (t); MS m/z 307 (M+, 14), 172 (36), 91 (100).
Anal. Calcd for C20H21NO2: C, 78.15; H, 6.89; N, 4.56. Found:
C, 78.10; H, 6.76; N, 4.51.
7-Bu t yl-2,3,4,5-t et r a h yd r oa zep in e-1-ca r b oxylic Acid
Ben zyl Ester (37). Compound 37 was prepared as reported
for 29 starting from 6 (93 mg, 0.25 mmol) and 26 (40 mg, 0.38
mmol), heating 7 h at 80 °C. Pure 37 (15 mg, 22%) was
obtained after chromatography (EtOAc-petroleum ether 1:4,
Rf 0.95) as an oil: 1H NMR (CDCl3) (1.5:1 mixture of rotamers)
δ 7.35-7.06 (m, 5 H), 5.40 (t, J ) 6.2 Hz, 1 H), 5.16 (s, 2 H),
3.70 (m, 2 H), 2.35-2.04 (m, 4 H), 1.86-1.17 (m, 8 H), 0.85
(m, 3 H) (major rotamer), 5.51 (t, J ) 6.5 Hz, 1 H), 5.14 (s, 2
H), and 3.78 (m, 2 H) (minor rotamer), 13C NMR (CDCl3) δ
153.6 (s), 136.4 (s), 130.1 (s), 129.1 (d), 128.4 (d, 2 C), 127.8
(d, 2 C), 115.8 (d), 66.8 (t), 47.7 (t), 37.9 (t), 28.1 (t), 26.7 (t),
25.1 (t), 24.6 (t), 22.4 (t), 13.9 (q); MS m/z 287 (M+, 1), 91 (100).
Anal. Calcd for C18H25NO2: C, 75.22; H, 8.77; N, 4.87. Found:
C, 75.12; H, 8.99; N, 4.52.
C
19H19NO2: C, 77.79; H, 6.53; N, 4.77. Found: C, 77.82; H,
6.54; N, 4.68.
6-Allyl-3,4-dih ydr o-2H-pyr idin e-1-car boxylic Acid Ben -
zyl Ester (32). Compound 32 was prepared as reported for 8
starting from 5 (92 mg, 0.25 mmol) and 24 (70 µL, 0.37 mmol),
but heating for 3 h at 80 °C. Pure 32 (42 mg, 65%) was
obtained after purification by chromatography (EtOAc-
petroleum ether 1:4, Rf 0.68) as a pale yellow oil: 1H NMR
(CDCl3) δ 7.34 (m, 5 H), 5.85-5.65 (m, 1 H), 5.14 (s, 2 H), 5.16-
4.93 (m, 3 H), 3.59 (m, 2 H), 3.21 (d, J ) 5.5 Hz, 2 H), 2.06 (m,
Ack n ow led gm en t. We thank MURST and the
University of Florence (COFIN 2000) and Consiglio
Nazionale delle Ricerche (CNR) for financial support.
Mr. Sandro Papaleo and Mrs. Brunella Innocenti are
acknowledged for their technical support.
J O001807C