Diastereoselective tandem addition-cyclization reactions of unsaturated tertiary amines initiated by photochemical electron transfer (PET)

Article abstract of DOI:10.1021/jo001166l

Polycyclic molecules and tetrahydroquinoleines were obtained in a tandem reaction involving the diastereoselective addition of α-aminoalkyl radicals to (5R)-5-menthyloxy-2[5H]-furanone 1. The facial diastereoselectivity on 1 is ≥90%. The α-aminoalkyl radicals were produced from tertiary amines by photochemical-induced electron transfer. When N, N-dialkylanilines 19 were used as starting tertiary amines, a rearomatization step was involved and important side reactions of 1 were observed. A mechanistic study involving isotopic labeling of the starting amine indicated that the byproducts resulted from reduction of I during the rearomatization process. An efficient optimization of the reaction was obtained by simply adding acetone or cyclopentanone as mild oxidants to the reaction mixture. The side products resulting from reduction of the furanone 1 were completely suppressed under these conditions, and the yields of the tetrahydroquinolines 21ai, 22a-f, and 26g-i were doubled.

Full text of DOI:10.1021/jo001166l

8690
J . Org. Chem. 2000, 65, 8690-8703
Dia ster eoselective Ta n d em Ad d ition -Cycliza tion Rea ction s of
Un sa tu r a ted Ter tia r y Am in es In itia ted by P h otoch em ica l Electr on
Tr a n sfer (P ET)
Samuel Bertrand, Norbert Hoffmann,* Ste´phane Humbel, and J ean Pierre Pete
Laboratoire de Re´actions Se´lectives et Applications, UMR CNRS et Universite´ de Reims
Champagne-Ardenne, UFR Sciences, B.P. 1039, F-51687 REIMS, Cedex 2, France
norbert.hoffmann@univ-reims.fr
Received J uly 31, 2000
Polycyclic molecules and tetrahydroquinoleines were obtained in a tandem reaction involving the
diastereoselective addition of R-aminoalkyl radicals to (5R)-5-menthyloxy-2[5H]-furanone 1. The
facial diastereoselectivity on 1 is g90%. The R-aminoalkyl radicals were produced from tertiary
amines by photochemical-induced electron transfer. When N,N-dialkylanilines 19 were used as
starting tertiary amines, a rearomatization step was involved and important side reactions of 1
were observed. A mechanistic study involving isotopic labeling of the starting amine indicated that
the byproducts resulted from reduction of 1 during the rearomatization process. An efficient
optimization of the reaction was obtained by simply adding acetone or cyclopentanone as mild
oxidants to the reaction mixture. The side products resulting from reduction of the furanone 1
were completely suppressed under these conditions, and the yields of the tetrahydroquinolines 21a -
i, 22a -f, and 26g-i were doubled.
In tr od u ction
benzophenone were used as sensitizers. Unfortunately,
the yields of these reactions were moderate and never
exceeded 60% despite the fact that the sensitizers were
used in stoichiometric amounts.6 Furthermore, large
quantities of reduction products, pinacols and other side
products resulting from a degradation of the sensitizer
or from a polymerization of the starting materials were
also observed.
Recently, we reported that the radical addition of
tertiary amines to electron-deficient alkenes became very
efficient when aromatic ketones, having electron-donor
substituents and T1 states with ππ* or charge-transfer
character, were used as a sensitizer.7-9 In contrast to
their analogues acetophenone and benzophenone, which
possess T1 states with nπ* character, the quantum yields
of photoreduction or pinacolization of aromatic ketones
having T1 states with ππ* or charge transfer character
Radical reactions have become an important tool in
preparative organic chemistry,1 but considerable efforts
are still needed to improve their selectivity to become
competitive with polar reactions.2
The radical addition of simple tertiary amines to
alkenes has been known for a long time.3 However, up
to now, the yields of these reactions were low to moderate,
independent of the initiation of the radical chain process.
Various methods have been proposed to produce R-
aminoalkyl radicals,4 but only few reports describe their
direct formation from tertiary amines. This type of
nucleophilic radicals can be easily added to electron-
deficient alkenes thus making available γ-aminobutyric
acid derivatives and a large variety of biological active
compounds. Among the initiation processes applied to
the generation of R-aminoalkyl radicals, the photo-
chemical electron transfer (PET)5 has also been tested,
and most frequently, ketones such as acetophenone and
(5) (a) Kavarnos, G. J . Fundamentals of Photoinduced Electron
Transfer; VCH: New York, 1993. (b) Mattay, J . Synthesis 1989, 233-
252. (c) Mattay, J .; Vondenhof, M. Top. Curr. Chem. 1991, 159, 219-
255. (d) Albini, A.; Fasani, E.; Mella, M. Top. Curr. Chem. 1993, 168,
143-173. (e) Pandey, G. Top. Curr. Chem. 1993, 168, 175-221. (f)
Lewis, F. Advances in Electron-Transfer Chemistry; Mariano, P. S.,
Ed.; J .A.I. Press Inc.: 1996; Vol. 5, pp 1-39. (g) Cossy, J .; Pete, J . P.
Advances in Electron-Transfer Chemistry; Mariano, P. S., Ed.; J .A.I.
Press Inc.: 1996; Vol. 5, pp 141-195. (h) Yoon, U. C.; Mariano, P. S.;
Givens, R. S.; Atwater, B. W., III Advances in Electron-Transfer
Chemistry; Mariano, P. S., Ed.; J .A.I. Press Inc.: 1994; Vol. 4, pp 117-
205. (i) Khim, S. K.; Cederstrom, E.; Ferri, D. C.; Mariano, P. S.
Tetrahedron 1996, 52, 3195-3222. (j) Photoinduced Electron Transfer,
Part A to D; Fox, M. A., Chanon, M., Eds.; Elsevier: Amsterdam, 1988.
(k) J ulliard, M.; Chanon, M. Chem. Rev. 1983, 83, 425-506. (l) Pandey,
G. Synlett 1992, 546-552.
(6) (a) Challand, B. D. Can. J . Chem. 1969, 47, 687-688. (b) Rubin,
G. M. B. Tetrahedron Lett. 1982, 23, 4615-4618. (c) de Alvarenga, E.
S.; Cardin, C. J .; Mann, J . Tetrahedron 1997, 53, 1457-1466.
(7) (a) Bertrand, S.; Glapski, C.; Hoffmann, N.; Pete, J . P. Tetra-
hedron Lett. 1999, 40, 3169-3172. (b) Bertrand, S.; Hoffmann, N.; Pete,
J . P. Tetrahedron Lett. 1999, 40, 3173-3174.
(8) Bertrand, S.; Hoffmann, N.; Pete, J . P. Eur. J . Org. Chem. 2000,
2227-2238.
(9) Turro, N. J . Modern Molecular Photochemistry; University
Science Books: Mill Valley, 1991.
(1) (a) Fossey, J .; Lefort, D.; Sorba, J . Free Radicals in Organic
Chemistry; Wiley: Chichester, 1995. (b) Giese, B. Radicals in Organic
Synthesis: Formation of Carbon-Carbon Bonds; Pergamon Press:
Oxford, 1986. (c) Curran, D. P. Comprehensive Organic Synthesis;
Trost, B. M., Fleming, I., Semmelhack, M. F., Eds.; Pergamon Press:
Oxford, 1991; Vol. 4, pp 715-777 and 779-831.
(2) Curran, D. P.; Porter, N. A.; Giese, B. Stereochemistry of Radical
Reactions; VCH: Weinheim, 1996.
(3) (a) Urry, W. H.; J uveland, O. O.; J . Am. Chem. Soc. 1958, 80,
3322-3328. (b) Cookson, R. C.; Hudec, J .; Mirza, N. A. J . Chem. Soc.,
Chem. Commun. 1968, 180. (c) de Alvarenga, E. S.; Mann, J . J . Chem.
Soc., Perkin Trans. 1 1993, 2141-2142. (d) Farrand, E.; Mann; J . J .
Chem. Soc., Perkin Trans. 1 1997, 1083-1084.
(4) (a) Renaud, P.; Giraud, L. Synthesis 1996, 913-926. For
structure and stability, see: (b) Wayner, D. D. M.; Clark, K. B.; Rauk,
A.; Yu, D.; Armstrong, D. A. J . Am. Chem. Soc. 1997, 119, 8925-8932.
(c) Dombrowski, G. W.; Dinnocenzo, J . P.; Farid, S.; Goodman, J . L.;
Gould, I. R. J . Org. Chem. 1999, 64, 427-431. For the nucleophilicity
of radicals, see also: (d) Giese, B.; Mehl, W. Tetrahedron Lett. 1991,
32, 4275-4278. (e) Lefort, D.; Fossey, J .; Sorba, J . New J . Chem. 1992,
16, 219-232. (f) Tedder, J . M. Angew. Chem., Int. Ed. Engl. 1982, 21,
401-410.
10.1021/jo001166l CCC: $19.00 © 2000 American Chemical Society
Published on Web 11/14/2000

Tandem Reactions of Unsaturated Tertiary Amines
J . Org. Chem., Vol. 65, No. 25, 2000 8691
Sch em e 1. P r op osed Mech a n ism for th e Efficien t Ster eoselective Ra d ica l Ad d ition of Ter tia r y Am in es to
Electr on -Deficien t Alk en es
Sch em e 2. P ossible P a th w a ys for Ra d ica l Ta n d em Rea ction s of Un sa tu r a ted Ter tia r y Am in es w ith
Electr on -Deficien t Alk en es
is only very small.10 However, if 4,4′-bis-N,N-dimethyl-
aminobenzophenone (Michler’s ketone) is used in the
presence of amines polymerization reactions can be
initiated.11 As a result of their lack of reactivity, aromatic
ketones with electron-donating substituents have rarely
been considered as efficient sensitizers in radical reac-
tions induced by PET.12,13 Nevertheless, we recently
found that the initiation of a radical chain by a PET
process between a tertiary amine and aromatic ketones
such as 4,4′-dimethoxybenzophenone as a sensitizer can
induce very efficient radical reactions. Interestingly, most
of the sensitizer could be recovered after the reaction,
despite the fact that it was used in very small quantities.
These observations led us to conclude that the efficiency
of the initiation process was due to the high delocalization
and stability of the aromatic ketyl radicals and to the
inefficient back electron transfer within the radical ion
pair.8 The efficient regeneration of the sensitizer was
explained by a hydrogen transfer from the ketyl radical
derived from the aromatic ketone to the oxoallyl radical
involved in the radical chain of cycle A (Scheme 1). The
chain process of cycle B was the result of a hydrogen
abstraction from the tertiary amine by the same oxoallyl
radical to regenerate the R-aminoalkyl radical and pro-
duce the final adduct. With N-alkyl pyrrolidines, the
radical is preferentially formed on the pyrrolidine ring.
The preference for nucleophilic radical addition to
electron-deficient alkenes led us to consider the reactivity
of N-alkenylpyrrolidines and aniline derivatives. In the
presence of electron-deficient alkenes in the reaction
mixture, either an intramolecular cyclization or an
intermolecular addition process could be possible with
the R-aminoalkyl radical and tandem reactions might be
expected. With N-allylpyrrolidines the intramolecular
process should be less favorable for reasons of ring strain,
and we anticipated that the intermolecular process might
be possible for the nucleophilic R-aminoalkyl radical.
After addition to the electron-deficient alkene, an elec-
trophilic radical intermediate should be formed in the
first step of a radical tandem process. In the second step,
an intramolecular attack of the electrophilic radical on
the electron-rich double bond should be realized by a
7-endo or 6-exo trig process. Finally, the products would
result from a hydrogen abstraction by the cyclized radical
intermediate as shown in Scheme 2.
(10) (a) Kavarnos, G. J .; Turro, N. J . Chem. Rev. 1986, 86, 401-
449. (b) Cohen, S. G.; Parola, A. H.; Parson, G. H., J r. Chem. Rev. 1973,
73, 141-161.
(11) Fouassier, J . P.; Ruhlmann, D.; Graff, B.; Morlet-Savary, F.;
Wieder, F. Prog. Org. Coat. 1995, 25, 235-271.
(12) Das, S.; Dileep Kumar, J . S.; Shivaramayya, K.; George, M. V.
J . Photochem. Photobiol. A 1996, 97, 139-150.
(13) Cossy, J .; Rakotoarisoa, H. Tetrahedron Lett. 2000, 41, 2097-
2099.

8692 J . Org. Chem., Vol. 65, No. 25, 2000
Bertrand et al.
Sch em e 3. Rea ction of N-Allylp yr r olid in e 2 w ith F u r a n on e 1 u n d er P h otoch em ica lly In d u ced Electr on
Tr a n sfer Con d ition s
Sch em e 4. F or m a tion of P er h yd r oa za a zu len e a n d In d olizid in e Der iva tives in th e Ra d ica l Ta n d em
Rea ction of th e Un sa tu r a ted Ter tia r y Am in e 4 w ith 1
We now report that the production of R-aminoalkyl
radicals by a PET process can be applied to the stereo-
selective radical tandem reaction14 of unsaturated ter-
tiary amines with the electron-deficient alkene (5R)-5-
menthyloxy-2[5H]-furanone 1. This chiral synthon, which
is readily available and frequently used in asymmetric
synthesis,15 has been recently applied to radical reac-
tions.7,8,16,17
To avoid this complication, we replaced 2 by the
dimethylated product 4. Four new compounds 5a ,b and
6a ,b were isolated in almost equal amounts, resulting
from a consecutive two-step radical process (Scheme 4).
The products correspond to endo trig (5a ,b) and exo trig
(6a ,b) cyclization. The configuration of all chiral centers
created during the reaction has been controlled, except
for the chiral center at the R position of the nitrogen
atom. As expected, the attack of the R-aminoalkyl radical
was highly stereoselective and anti with respect to the
menthyloxy substituent on the furanone 1.
Resu lts a n d Discu ssion
Ad d ition of N-Allylp yr r olid in e Der iva tives to
(5R)-5-Men th yloxy-2[5H]-fu r a n on e 1. We started our
investigation by irradiating a solution of N-allylpyrroli-
dine 2, (5R)-5-menthyloxy-2[5H]-furanone 1, and cata-
lytic amounts (5 mol %) of 4,4′-dimethoxybenzophenone
as sensitizer. No radical addition of R-aminyl radicals to
the furanone 1 could be observed in the reaction mixture.
The only new product (3), which could be isolated,
resulted from a Michael reaction (Scheme 3),8 indicating
that pyrrolidine had been liberated during the irradia-
tion. This secondary amine, known to add rapidly to 1,18
might be initiated by hydrogen abstraction on the allyl
side chain.
When the alkyne derivative 7 was irradiated under the
same conditions, a higher regioselectivity was observed
(Scheme 5), with the formation of only endo dig products
8 (32%) and 9 (29%). Here again, the attack of the
R-aminoalkyl radical was highly stereoselective and anti
with respect to the menthyloxy substituent, while the
configuration of the chiral center at the R position of the
nitrogen atom was not controlled. Formation of the
conjugated lactone 9 implied an isomerization process of
the deconjugated intermediate 10, which could not be
characterized in the reaction mixture. Under the reaction
conditions, a corresponding conjugated product is not
formed from lactone 8. Furthermore, when 8 was dis-
solved in triethylamine, no isomerization could be de-
tected after 1 week at room temperature.
(14) For the concept of tandem or domino reactions, see: (a) Tietze,
L. F.; Beifuss, U. Angew. Chem., Int. Ed. Eng. 1993, 32, 131-163. (b)
Tietze, L. F. Chem. Rev. 1996, 96, 115-136.
(15) (a) Martel, J .; Tessier, J .; Demoute, J . P. European Patent 23454
(Roussel Uclaf) 1981. (b) Feringa, B. L.; De Lange, B.; J ansen, J . F. G.
A.; De J ong, J . C.; Lubben, J . C.; Faber, W.; Schudde, E. P. Pure Appl.
Chem. 1992, 64, 1865-1871. (c) Feringa, B. L.; De J ong, J . C. Bull.
Soc. Chim. Belg. 1992, 101, 627-640.
(16) Bertrand, S.; Hoffmann, N.; Pete, J . P.; Bulach, V. Chem.
Commun. 1999, 2291-2292.
(17) (a) Hoffmann, N. Tetrahedron: Asymmetry 1994, 5, 879-886.
(b) Belokon, Y. N.; Kotchekov, K. A.; Moskalenko, M. A.; Raevsky, N.
I.; Saveleva, T. F.; Tararov, V. I.; Churkina, T. D. Izv. Akad. Nauk,
Ser. Khim. 1995, 534-536.
The structure and the relative configuration of 5a ,b,
8, and 9 have been determined by using NMR spectros-
copy. The configuration of the asymmetric carbon created
at the R position to the nitrogen was determined by NOE
measurements (Scheme 6). The absence of the NOE on
H4, when the irradiation was carried out on the acetal
(18) de Lange, B.; van Bolhuis, F.; Feringa, B. L. Tetrahedron 1989,
45, 6799-6818.

Tandem Reactions of Unsaturated Tertiary Amines
J . Org. Chem., Vol. 65, No. 25, 2000 8693
Sch em e 5. Ra d ica l Ta n d em Rea ction of N-(3,3-Dim eth ylp r op in -3-yl)p yr r olid in e 7 w ith 1
Sch em e 6. Deter m in a tion of th e Con figu r a tion of
Com p ou n d s 5a , 5b, 8, a n d 9 by NOE Mea su r em en ts
proton H5, additionally confirmed the radical attack anti
with respect to the menthyloxy substituent.
Compounds 6a ,b and 7a , which possess NMR data
very similar to the corresponding data of analogues 5a ,b,
also result from an anti addition of the R-aminoalkyl
radical on the lactone ring. Furthermore, the stereo-
chemistry of the methyl group at 3′′ appeared to be the
same for 6a and 6b. The coupling constant J (H3′′,H3) ) 4.5
Hz in both compounds indicated an anti orientation of
the hydrogen atoms.19
To explain why the conjugation of the unsaturated
lactone depends on the configuration at C5′′ and why the
F igu r e 1. Shape of the isomers 11-14 as optimized at the
corresponding enol intermediate led by tautomerization
to the conjugated and compound 9, we carried out a
theoretical investigation. To save computational require-
ments, we replaced the menthyloxy substituent by a
methoxy group and we optimized the structures of the
corresponding deconjugated lactones 11 and 14 and their
conjugated isomers 13 and 12, respectively (Figure 1).
Our investigation started with a conformational search.20,21
B3LYP/6-31G level of calculation. The nitrogen atom is dark,
and the oxygen atoms are gray.
The structures of lowest energy were reoptimized22 at the
Density Functional Theory level B3LYP/6-31G for a
better comparison of the energies of the various com-
pounds.
These results show that the compounds 12 and 13
possessing a conjugate CdC double bond are more stable
than their isomers 11 and 14. The energy gain by
conjugation with the CdO bond is almost the same for
both diastereoisomers 13 and 12 (Table 1). Therefore,
thermodynamic stability cannot explain why the isomer
(19) Gosselin, P.; Bourdy, C.; Mille, S.; Perrotin, A. J . Org. Chem.
1999, 64, 9557-9565.
(20) One thousand structures were requested to be processed. The
lowest structures of each compound were found about 80 times.
(21) (a) Macromodel 6.0, Columbia University, 1997. (b) Allinger,
N. L.; Yuh, Y. H.; Lii, J .-H. J . Am. Chem. Soc. 1989, 111, 8552-8566.

8694 J . Org. Chem., Vol. 65, No. 25, 2000
Bertrand et al.
Sch em e 7. Ra d ica l Ta n d em Rea ction of N,N-Dim eth yla n ilin e 19a a n d F u r a n on e 1 u n d er P ET Con d ition s
Ta ble 1. Den sity F u n ction n a l Th eor y (B3LYP )
Com p u ta tion a l Resu lts Usin g th e 6-31G Ba sis Set u n less
Oth er w ise Sp ecified
addition of N,N-dimethylaniline 19a . When a solution of
1 was irradiated in the presence of a large excess of N,N-
dimethylaniline 19a and a catalytic amount of Michler’s
ketone 20 as sensitizer, we obtained the tetrahydro-
quinolines 21a and 22a with a diastereomeric excess of
90%. (Scheme 7). Similar tandem reactions have already
been reported to give low yields or to result from side
reactions.23,24 Unfortunately, in our preliminary experi-
ments, the isolated yields were also low and the side
products 23 and 24, resulting from the reduction of 1,
were obtained in similar amounts. Normally, the ef-
ficiency of forming the reductive duplication product 24
should be sensitive to the relative concentration of the
starting materials. Accordingly, when the concentration
of 1 (5 × 10-3 mol L-1) was decreased, the side product
24 disappeared from the reaction mixture, while the yield
of the lactone 23 increased (23%). On the basis of the
NMR data, we established that the adducts 21a and 22a
contained a tetrahydroquinoline structure. The configu-
ration of the major isomer 21a was determined by X-ray
analysis.16
DFT B3LYP
absolute energy (au)
relative energy (kcal/mol)
11
13
14
12
-826.27969
-826.28777
-826.28173
-826.29096
0.0
-5.1
-1.3
-7.1
-5.1
-5.8
15
16
-826.24279
-826.25006
+23.2
+18.6
-4.6
17
18
-825.74151a
-825.75403a
-7.9a
a
6-31+G basis set.
13 was not formed by tautomerization of 11 in basic
conditions. To get some information on the kinetic
control, we also performed calculations on the corre-
sponding dienol (15, 16) and dienolate (17, 18) intermedi-
ates (Table 1, Figure 2). As required by the anionic
character of the dienolates, diffuse functions were added
to the basis set B3LYP/6-31+G. In the case of the
dienolates the calculations show a significant energy
difference between the two diastereoisomers 17 and 18
(7.9 kcal). That 17 is less stable is certainly due to the
fact that the torsion angle between the CdC bond and
the enolate moiety is about 153° (compared to 171° for
18), which diminishes the conjugation. The difference
between this torsion angle is even more important for
the corresponding dienols 15 (140°) and 16 (167°).
From these calculations, we conclude that the absence
of isomerization for 8 (Scheme 5) might be due to kinetic
reasons and especially to the difficulty in obtaining the
corresponding enol or enolate.
On the basis of these observations, we concluded that
the formation of the desired tetrahydroquinolines 21a
and 22a and the formation of the side products 23 and
24 could be linked. As tetrahydroquinoline derivatives
possess a great pharmaceutical interest,25 we tried to
optimize the reaction and reduce or eliminate the forma-
tion of byproducts. To improve the synthesis and to verify
the origin of the side reactions of 1, we carried out the
reaction with the aniline derivatives 19a ′ and 19a ′′
deuterated at the ortho and para position of the aromatic
ring or at the N-methyl groups respectively (Scheme 8).
In the presence of 19a ′, a deuterium transfer to the
furanone 1 was observed at the R position of the lacton
group of 23′ and at one of the corresponding positions of
the bislactone 24′. When the reaction was carried out
with amine 19a ′′ possessing two CD3 groups, deuterium
transfer could be detected at the â position of the lactone
23′′ and again at one of the R positions of the bislactone
24′.
Ad d ition of N,N-Dia lk yla n ilin e Der iva tives to 1.
To extend the scope of the radical tandem reactions, we
became interested in reactions of aromatic tertiary
amines under similar conditions. We first examined the
(22) Gaussian 98, Revision A.7; Frisch, M. J .; Trucks, G. W.;
Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; Cheeseman, J . R.;
Zakrzewski, V. G.; Montgomery, J r. J . A.; Stratmann, R. E.; Burant,
J . C.; Dapprich, S.; Millam, J . M.; Daniels, A. D.; Kudin, K. N.; Strain,
M. C.; Farkas, O.; Tomasi, J .; Barone, V.; Cossi, M.; Cammi, R.;
Mennucci, B.; Pomelli, C.; Adamo, C.; Clifford, S.; Ochterski, J .;
Petersson, G. A.; Ayala, P. Y.; Cui, Q.; Morokuma, K.; Malick, D. K.;
Rabuck, A. D.; Raghavachari, K.; Foresman, J . B.; Cioslowski, J .; Ortiz,
J . V.; Baboul, A. G.; Stefanov, B. B.; Liu, G.; Liashenko, A.; Piskorz,
P.; Komaromi, I.; Gomperts, R.; Martin, R. L.; Fox, D. J .; Keith, T.;
Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Gonzalez, C.; Challa-
combe, M.; Gill, P. M. W.; J ohnson, B.; Chen, W.; Wong, M. W.; Andres,
J . L.; Gonzalez, C.; Head-Gordon, M.; Replogle, E. S.; Pople, J . A.;
Gaussian, Inc.: Pittsburgh, PA, 1998.
(23) (a) Fayadh, J . M.; Swan, G. A. J . Chem. Soc. C 1969, 1781-
1784. (b) Roy, R. B.; Swan, G. A. J . Chem. Soc. C 1969, 1886-1891.
(c) Murata, S.; Termoto, K.; Miura, M.; Nomura, M. Hetereocycles 1993,
36, 2147-2153. (d) Araneo, S.; Fontana, F.; Minisci, F.; Recpero, F.;
Serri, A. Tetrahedron Lett. 1995, 36, 4307-4310. (e) Mattay, J .;
Banning, A.; Bischof, E. W.; Heidbreder, A.; Runsink, J . Chem. Ber.
1992, 125, 2119-2127.
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52, 15031-15070.

Tandem Reactions of Unsaturated Tertiary Amines
J . Org. Chem., Vol. 65, No. 25, 2000 8695
F igu r e 2. Shape of the enols 15 and 16 as optimized at the B3LYP/6-31G level of calculation. Shape of the enolates 17 and 18
as optimized at the B3LYP/6-31+G level of calculation. The nitrogen atom is dark, and the oxygen atoms are gray. The number
in degrees indicates the dihedral angle between the double bonds.
Sch em e 8. Ra d ica l Ta n d em Rea ction of th e Deu ter a ted N,N-Dim eth yla n ilin es 19a ′ a n d 19a ′′ a n d
F u r a n on e 1a
a
The degree of deuteration in the products has been determined by signal integration of the corresponding protons in the 1H NMR
spectra.
The degree of deuteration was determined by integra-
tion of the corresponding signals of the H NMR spectra.
The intensity of the signals at 2.41 and 2.65 ppm for the
protons at R position of lactone 23′ and at 2.28 ppm for
the â protons of lactone 23′′ were decreased with respect
to the non deuterated analogues. The same effect was
observed for the signal at 2.81 ppm for the one proton at
the R position of the bis lactone 24′.
The results of the isotopic labeling experiments can
be explained by the mechanism depicted in Scheme 9.
1

8696 J . Org. Chem., Vol. 65, No. 25, 2000
Bertrand et al.
Sch em e 9. Mech a n ism of th e Ra d ica l Ta n d em Rea ction of th e Deu ter a ted N,N-Dim eth yla n ilin es 19a ′ a n d
19a ′′ a n d F u r a n on e 1
During the initiation step, nucleophilic R aminoalkyl
radicals A are generated via a photochemical induced
electron transfer.5,26 After addition to 1, the electrophilic
oxoallyl radical B adds to the phenyl ring by an intramo-
lecular reaction. A rearomatization process is needed to
produce the final products 21a ′ and 22a ′.
information is available on the nature of the oxidant and
the mechanistic details.24 After deuterium transfer to 1,
an O-deuterated oxyallyl radical D is produced. Then, D
undergoes a hydrogen abstraction from the methyl group
of 19a ′. After tautomerization, lactone 23′ is obtained
possessing one deuterium at the R position.
During the process, a deuterium is transferred from
the former ortho position of the aromatic ring to 1.
Although such rearomatization processes are frequently
observed in photochemical and radical reactions, little
The deuterium transfer from the methyl group of 19a ′′
to the â position of the lactone 23′′ can be explained by
the same mechanism. In this case, deuterium transfer
from the CD3 group of 19a ′′to the â position of the
hydroxyallyl radical D occurs.
(26) (a) Peters, K. S.; Cashin, A.; Timbers, P. J . Am. Chem. Soc.
2000, 122, 107-113. (b) Dreyer, J .; Peters, K. S. J . Phys. Chem. 1996,
100, 19412-19416. (c) Zhang, X.; Yeh, S.-R.; Hong, S.; Freccero, M.;
Albini, A.; Falvey, D. E.; Mariano, P. S. J . Am. Chem. Soc. 1994, 116,
4211-4220. (d) Pac, C.; Tosa, T.; Sakurai, H. Bull. Chem. Soc. J pn.
1972, 45, 1169-1175. (e) Su, Z.; Falvey, D. E.; Yoon, U. C.; Mariano,
P. S. J . Am. Chem. Soc. 1997, 119, 5261-5262. (f) Su, Z.; Mariano, P.
S.; Falvey, D. E.; Yoon, U. C.; Oh, S. W. J . Am. Chem. Soc. 1998, 120,
10676-10686. (g) Arimitsu, S.; Masuhara, H.; Mataga, N.; Tsubomura,
H. J . Phys. Chem. 1975, 79, 1255-1259. (h) Hendriks, B. M. P.; Walter,
R. I.; Fischer, H. J . Am. Chem. Soc. 1979, 101, 2378-2383. (i)
Bartholomew, R. F.; Davidson, R. S. J . Chem. Soc. (C) 1971, 2342-
2346. (j) Do¨pp, D.; Heufer, J . Tetrahedron Lett. 1982, 23, 1553-1556.
(k) Lin, J . Ph.D. Thesis, Universita¨t Gesamthochschule Duisburg, 1994.
To explain the incorporation of a deuterium atom at
only one R position of compound 24′, the addition of the
O-deuterated oxyallyl intermediate D to 1, followed by
hydrogen abstraction from the N-methyl groups of 19a ′,
has to be considered. When 19a ′′ was used, the deuterium
transfer from the CD3 group to the intermediate E occurs.
The labeling experiments indicate that a hydrogen
atom has to be transferred to the oxygen atom of a
carbonyl group. Such an unusual transfer might involve
a two-step process. First, a single electron transfer

Tandem Reactions of Unsaturated Tertiary Amines
J . Org. Chem., Vol. 65, No. 25, 2000 8697
Sch em e 10. Rea r om a tiza tion Step of th e F or m a tion of th e Tetr a h yd r oqu in olin e Der iva tives 21a a n d 22a
Ta ble 2. Rea ction of F u r a n on e 1 w ith
N,N-Dim eth yla n ilin e 19a in th e P r esen ce of Keton es a s
the R position of the amine nitrogen was not controlled.
Similar results were already obtained for the radical
Mild Oxid a n ts
addition of simple tertiary amines to electron-deficient
quantity irradiation timea yield of 21a , 22a
alkenes such as 1.7,8 The reaction of 1 with N-phenyl-
pyrrolidine 19h and N-phenylpiperidine 19i under the
same conditions produced benzoindolizidine (21h , 26h )
and benzoquinolizidine derivatives (21i, 26i), repectively.
It has to be noted that the stereoselectivity was higher
when phenylpiperidine 19i was used as the tertiary
amine.
ketone
acetone
(equiv)
(min)
(%)
5
30
solv
5
360
360
420
360
73
77
71
78
acetone
acetone
cyclopentanone
a
Michler’s ketone 20 was used as sensitizer.
The relative configurations of 21g and 26g have been
determined by NOE measurements (Scheme 14). The
structure of 21h ,i and 26h ,i was assigned by comparison
with 21g and 26g, which present analogue NMR data.
When radicals add to disubstituted sp2 carbons, an
important rate decrease is observed. To test the influence
of two ortho substituents on the addition process, we next
examined the reactivity of 27 with two protected ortho
positions of the aromatic ring. In the reaction of N-
mesitylpyrrolidine 27 with 1, no tandem reaction could
be detected in the reaction mixture. Two addition prod-
ucts 28 and 29 were formed in a faster reaction very
similar to the radical reaction of N-alkylpyrrolidine
derivatives to electron-deficient alkenes such as 1 (Scheme
15).7,8 The high reactivity observed for 27 can be ex-
plained by a suppression of nitrogen lone pair conjugation
with the aromatic π-system. As a result of steric hin-
drance of the ortho methyl groups, the aryl ring and the
pyrrolidine ring are oriented in an orthogonal arrange-
ment. Interestingly, the important steric hindrance of
the mesityl substituent also causes an increase in the
diastereoselectivity of the chiral center formed at the R
position of the nitrogen atom. The diastereomeric ratio
of 80:20 differs significantly from the ratio of 55:45
generally observed for the radical addition of N-alkyl-
pyrrolidine derivatives.8
between the radical C and the carbonyl might produce a
well stabilized carbenium ion F and an enolate anion G
(Scheme 10). After consecutive proton (deuterium) trans-
fer from F to G, a hydroxyallyl radical such as the
intermediate D and the final products 21a and 22a would
be formed.
As shown in Scheme 9, the furanone 1 can act as an
electrophilic alkene as well as an oxidant in the rearo-
matization step of radical C. To avoid the formation of
the side products 23 and 24 and to make the reaction
more efficient and applicable in organic synthesis, 1 had
to be replaced by a mild oxidant in the oxidation step.
We considered that simple ketones might play this role.
When acetone or cyclopentanone were added in excess
to the reaction mixture, the formation of side products
was completely suppressed while the yields of tetra-
hydroquinolines were doubled (Table 2). Under these
reaction conditions, ketyl radicals H were also generated
(Scheme 11). Such nucleophilic radicals are known to add
efficiently to 1.17 When indeed acetone or cyclopentanone
were introduced in the reaction mixture, we could detect
traces of the corresponding product 25.
We wondered if aliphatic ketones could replace aro-
matic ketones in the initiation of the radical process.
When the irradiation of 1 and N,N-dimethylaniline was
carried out at λ ) 300 or 350 nm in the presence of a
large excess of acetone but in the absence of the sensitizer
20, only a slow and very unselective reaction was
observed. The complex mixture obtained under these
conditions is very similar to what is obtained for a radical
addition of tertiary amines to alkenes when conventional
sensitizers such as acetophenone or benzophenone are
used to induce the electron transfer.6-8
Under optimized conditions, we next examined the
reaction of 1 with several N,N-dimethylaniline deriva-
tives (19a -f) (Scheme 12). In all cases, the tetrahydro-
quinoline derivatives (21a -f and 22a -f) were obtained
in high yield with 90% de. The reaction of the meta
toluidine derivative 19e yielded regioisomers 21e, 22e
and 21′e, 22′e. The azasteroid like compounds 21f, 22f
were obtained from the reaction of the tetrahydronaph-
thylamine derivative 19f.
When the reaction was carried out with other N,N-
dialkylated aniline derivatives, like N,N-diethylaniline
19g, the radical attack occurred diastereospecifically anti
with respect to the menthyloxy substituent of 1 (Scheme
13). However, the configuration of the chiral center at
Con clu sion
We have described an efficient and diastereoselective
tandem addition reaction, involving a radical process,
between (5R)-5-menthyloxy-2[5H]-furanone 1 with N,N-
dialkylanilines and pyrrolidine derivatives possessing
an unsaturated side chain on the nitrogen atom. Poly-
cyclic molecules having a tetrahydroquinoline skeleton,
indolizidine, benzoquinolizidine, and perhydroazaazulene
derivatives, were obtained in this way. The radical chain
process was initiated by a photochemically induced
electron transfer. During the reaction of the N,N-dialkyl-
anilines, considerable amounts of reduction products of
1 were formed in side reactions. A mechanistic study,
based on isotopically labeled N,N-dimethylaniline, indi-
cated that the furanone 1 was involved in a rearomati-
zation step. When ketones such as acetone or cyclo-
pentanone were added to the reaction mixture as hydro-
gen acceptors, the yield of the tetrahydroquinoline de-
rivatives doubled and the formation of reduction side
products was completely suppressed.

8698 J . Org. Chem., Vol. 65, No. 25, 2000
Bertrand et al.
Sch em e 11. Rea r om a tiza tion Step of th e F or m a tion of th e Tetr a h yd r oqu in olin e Der iva tives 21a a n d 22a
in th e P r esen ce of Keton es a s Mild Oxid a n ts
Sch em e 12. Asym m etr ic Syn th esis of Tetr a h yd r oqu in olin e a n d Aza ster oid Der iva tives by th e Ra d ica l
Ta n d em Ad d ition of N,N-Dim eth yla n ilin e Der iva tives w ith 1
241 Polarimeter. Acetonitrile was dried with calcium hydride,
then with magnesium sulfate before distillation. Starting
amines were dried and distillated on calcium hydride. (5R)-
5-Menthyloxy-2-[5H]-furanone 1 was prepared from furfural
and (-)-menthol according to literature procedure.15
Irradiations of the solution were carried out in Pyrex tubes
(Φ ) 1 cm), at 350 nm, with a Rayonet apparatus (model RPR-
100) from the Southern New England Ultraviolet Company.
Solutions were degassed with argon before irradiation. HPLC
chromatography was carried out on a SHIMADZU LC-10AS
(detector, UV SPD-10A; column, Lichrosorb Si60 7 µm; length
) 25 cm, i.d. ) 9 mm, o.d. ) 0.5 in.
Exp er im en ta l Section
Gen er a l Meth od s. 1H NMR and 13C NMR spectra were
recorded with a Bruker AC 250 (250 MHz for 1H and 62 MHz
1
for 13C) or Bruker DRX 500 (500 MHz for H and 126 MHz for
13C). Coupling constants are reported in hertz. Chemical shifts
are given in ppm relative to tetramethylsilane as an internal
standard. IR spectra were recorded with MIDAC Prospect IR
(FTIR). MS spectra were recorded with J EOL D-300. Prepara-
tive chromatography was carried out with Merck 9385
Kieselgel 60. GC was carried out on a Hewlett-Packard
6890HP with a capillary column (HP-1). Specific rotation
values were recorded in CH2Cl2 as solvent with a Perkin-Elmer

Tandem Reactions of Unsaturated Tertiary Amines
J . Org. Chem., Vol. 65, No. 25, 2000 8699
Sch em e 13. Asym m etr ic Syn th esis of Nitr ogen -Con ta in in g P olycyclic Com p ou n d s by Ra d ica l Ta n d em
Ad d ition of N,N-Dia lk yla n ilin e Der iva tives 19g-i w ith 1
mmol) in 20 mL of ethanol was added to 1,4-dibromobutane.
The mixture was then stirred at 60 °C for 72 h. A solution of
K2CO3 (10%) and 100 mL ether was added. The organic phase
was washed with brine and dried over MgSO4. The solvent
was evaporated, and the residue was recrystallized from ethyl
Sch em e 14. Deter m in a tion of th e Con figu r a tion
of Com p ou n d s 21g a n d 26g by NOE Mea su r em en ts
1
acetate/petroleum ether. Yield: 24.11 g (88%). Mp: 75 °C. H
NMR (250 MHz, CDCl3): δ 1.41 (s, 6H), 1.80 (m, 4H), 2.23 (s,
1H), 2.72 (m, 4H). 13C NMR (62 MHz, CDCl3): δ 23.6, 29.4,
47.9, 53.6, 71.1, 85.4. IR (KBr): ν 3135, 2970, 2810, 2080, 1455,
1365, 1190, 1015.
A solution of (5R)-5-menthyloxy-2[5H]-furanone 1 (950 mg,
4 mmol), the pyrrolidine derivative 4 or 7 (16 mmol), and
4,4′dimethoxybenzophenone (45 mg, 0.2 mmol) in acetonitrile
(80 mL) was irradiated at 350 nm for 4 h. In the case of the
reaction of 4, the solvent and the excess of the unsaturated
amine were evaporated and the residue was subjected to flash
chromathography (eluent, ethyl acetate/petroleum ether 1/5).
In the case of the reaction of 7, most of the solvent was
evaporated. The residue (mixture of crystals of 7 and reaction
products) was washed with petroleum ether. The solvent of
the washing solution was evaporated and the residue residue
was subjected to flash chromathography (eluent, ethyl acetate/
petroleum ether 1/5).
Rea ction of (5R)-5-Men th yloxy-2-[5H]-fu r a n on e 1 w ith
N-(1,1-Dim eth yla llyl)p yr r olid in e 4 a n d N-(1,1-Dim eth yl-
p r op a r gyl)p yr r olid in e 7. P r ep a r a tion of Am in e 4. Product
P er h yd r oa za a zu len e Der iva tive 5a . Yield: 257 mg
4 was synthesized according to a literature procedure.27
A
(17%). Mp: 112 °C. [R]21D: -96.7. [R]21578: -99.5. [R]21
:
546
solution of vinylmagnesium chloride (23.7 mL, 40 mmol) was
added dropwise to a solution of 2-methyl-2-pyrrolidinonitrile
(5.5 g, 40 mmol) in THF (40 mL) that was cooled to 0 °C. The
solution was then stirred at room temperature for 4 h. Diethyl
ether (100 mL) was added. The resulting solution was washed
with water. The aqueous phase was extracted twice with
diethyl ether (50 mL). The combined organic phases were dried
with MgSO4. The solvent was evaporated, and the residue was
-103.4. [R]21436: -188.6. [R]21365: -210.3 (c ) 1.68). 1H NMR
(250 MHz, CDCl3): δ 0.77 (d, J ) 6.9, 3H), 0.85 (d, J ) 6.9,
3H), 0.91 (d, J ) 7.6, 3H), 0.92 (s, 3H), 0.68-1.02 (m, 3H),
1.04 (s, 3H), 1.08-1.47 (m, 4H), 1.52-1.68 (m, 4H), 1.69-2.14
(m, 6H), 2.37 (ddd, J ) 9.8, 4.6, 2.2, 1H), 2.61-2.82 (m, 2H,)
2.92 (m, 1H), 3.21 (ddd, J ) 10.3, 4.6, 2.3, 1H), 3.57 (td, J )
10.7, 4.2, 1H), 5.82 (d, J ) 4.6,1H). 13C NMR (62 MHz,
CDCl3): δ 15.7, 15.8, 20.9, 22.3, 23.0, 23.1, 24.6, 25.3, 30.8,
31.3, 31.8, 34.3, 39.9, 41.5, 43.7, 47.8, 49.5, 50.3, 53.9, 54.2,
76.9, 101.7, 178.6. IR (KBr): ν 2955, 2915, 2865, 1785, 1260,
1145, 945. MS m/z (relative intensity): 377 (M+, 3.7), 362 (100),
318 (27), 238 (12), 224 (11), 194 (21), 150 (5), 112 (16).
distilled under reduced pressure. Yield: 3.12 g (56%). Bp20
:
58 °C. 1H NMR (250 MHz, CDCl3): δ 1.11 (s, 6H), 1.57 (m,
4H), 2.53 (m, 4H), 4.95 (d, J ) 6.2, 1H), 5.02 (d, J ) 0.8, 1H),
5.87 (dd, J ) 6.2, 0.8, 1H). 13C NMR (62 MHz, CDCl3): δ 23.7,
24.2, 46.0, 56.0, 112.5, 143.7.
Anal.Calcd for
C23H39NO3: C, 73.10; H, 10.34; N, 3.71.
P r ep a r a t ion of Am in e 7.28 A mixture of 1,1-dimethyl-
propargylamine (16.6 g, 200 mmol) and K2CO3 (13.8 g, 100
Found: C, 73.03; H, 10.00; N, 3.65.
P er h yd r oa za a zu len e Der iva tive 5b. Yield: 211 mg
(14%). Mp: 121 °C. [R]21D: -81.4. [R]21578: -85.0. [R]21546: -96.3.
[R]21436: -161.6. [R]21365: -191.3 (c ) 0.88). 1H NMR (250 MHz,
CDCl3): δ 0.73 (d, J ) 6.9, 3H), 0.82 (d, J ) 6.9; 3H), 0.83 (s,
3H), 0.91 (d, .J ) 6, 3H), 0.68-1.06 (m, 3H), 1.04 (s, 3H), 1.12-
1.42 (m, 4H), 1.45-1.87 (m, 7H), 1.92-2.17 (m, 3H), 2.62 (dd,
(27) Trost, B. M.; Spagnol, M. D. J . Chem. Soc., Perkin Trans. 1
1995, 2083-2096.
(28) (a) Hennion, G. F.; Nelson, K. W. J . Am. Chem. Soc. 1957, 79,
2142-2145. (b) Hennion, G. F.; Perrino, A. C. J . Org. Chem. 1961, 26,
1073-1079.

8700 J . Org. Chem., Vol. 65, No. 25, 2000
Sch em e 15. Ra d ica l Ad d ition of N-Mesitylp yr r olid in e 27 to 1
Bertrand et al.
J ) 7.2, 4.6,1H), 2.61-2.91 (m, 3H), 2.98 (ddd, J ) 8.2, 4.6,
2.2, 1H), 3.43 (td, J ) 10.7, 4.2, 1H), 5.28 (s, 1H).13C NMR (62
MHz, CDCl3): δ 15.6, 19.1, 20.4, 20.8, 22.3, 23.1, 24.0, 25.5,
28.1, 31.3, 31.4, 34.3, 39.6, 40.1, 41.9, 47.7, 47.8, 52.9, 54.1,
54.2, 76.1, 101.3, 179.3. IR (KBr): ν 2960, 2920, 2870, 1780,
1455, 1365, 1105, 955. MS m/z (relative intensity): 377 (M+,
3.7), 362 (27), 318 (12), 238 (100), 224 (16), 194 (8), 150 (7),
112 (11). Anal. Calcd for C23H39NO3: C, 73.10; H, 10.34; N,
3.71. Found: C, 72.78; H, 10.19; N, 3.59.
0.92 (s, 3H), 0.67-1.02 (m, 3H), 1.10-1.42 (m, 2H), 1.20 (s,
3H), 1.53-2.11 (m, 8H), 2.18 (dd, J ) 14.9, 9.2, 1H), 2.53 (m,
1H), 2.61 (m, 1H), 2.63 (dd, J ) 14.9, 7.2, 1H), 2.80 (m, 1H),
3.07 (m, 1H), 3.51 (td, J ) 10.7, 4.2, 1H), 5.33 (d, J ) 3.8, 1H),
6.89 (ddd, J ) 9.2, 7.2, 3.0, 1H).13C NMR (62 MHz, CDCl3): δ
15.8, 15.9, 20.3, 20.8, 22.3, 23.1, 25.3, 29.4, 31.3, 32.1, 34.3,
39.4, 42.5, 47.8, 48.5, 51.9, 55.8, 56.4, 77.3, 100.8, 132.3, 139.4,
168.5. IR (KBr): ν 2960, 2925, 1770, 1465, 1115, 940. MS m/z
(relative intensity): 375 (M+, 9), 360 (37), 236 (23), 219 (10),
Qu in olizid in e Der iva tive 6a . Yield: 241 mg (16%). Mp:
178 (8), 148 (14), 136 (29), 111 (100). Anal. Calcd for C23H37-
NO3: C, 73.56; H, 9.93; N, 3.73. Found: C, 73.33; H, 9.82; N,
3.48.
89 °C. [R]21D: -102.3. [R]21578: -107.6. [R]21546: -123.53. [R]21436:-
1
162.5. [R]21365: -209.3 (c ) 0.96). H NMR (250 MHz, CDCl3):
δ 0.71 (d, J ) 6.9, 3H), 0.80 (d, J ) 6.9,3H), 0.83 (d, J ) 6.2,
3H), 0.85 (s, 3H), 0.93 (d, J ) 7.6, 3H), 0.68-1.02 (m, 3H),
1.12 (s, 3H), 1.12-1.42 (m, 4H), 1.47-1.82 (m, 5H), 1.96-2.42
(m, 4H), 2.59-2.71 (m, 2H), 2.98 (ddd, J ) 9.3, 4.1, 2.2, 1H),
3.55 (td, J ) 10.7, 4.2, 1H), 5.80 (d, J ) 6.1, 1H).13C NMR (62
MHz, CDCl3): δ 13.4, 15.8, 20.9, 22.3, 22.9, 23.1, 24.2, 25.2,
27.1, 27.1, 31.4, 34.3,40.3, 41.3, 43.9, 46.0, 47.7, 48.0, 52.2, 55.4,
78.2, 100.8, 176.4. IR (KBr): ν 2960, 2875, 1780, 1450, 1355,
955. MS m/z (relative intensity): 377 (M+, 3.7), 362 (100), 318
(27), 238 (12), 224 (11), 194 (21), 150 (5), 112 (16). Anal. Calcd
for C23H39NO3: C, 73.10; H, 10.34; N, 3.71. Found: C, 72.82;
H, 10.06; N, 3.55.
Rea ction of (5R)-5-Men th yloxy-2-[5H]-fu r a n on e 1 w ith
N,N-Dim eth yla n ilin e 19a . A solution of (5R)-5-menthyloxy-
2[5H]-furanone 1 (300 mg, 1.26 mmol), N,N-dimethylaniline
(2.42 g, 20 mmol), and Michler’s ketone 20 (30 mg, 0.1 mmol)
in acetonitrile (10 mL) was irradiated at 350 nm for 7 h. The
solvent was evaporated, and the residue was subjected to flash
chromathography (eluent, ethyl acetate/petroleum ether 1/5).
The tetrahydroquinoline derivatives 21a and 22a were sepa-
rated by HPLC.
Tetr a h yd r oqu in olin e Der iva tive 21a . Yield: 171 mg
(38%). Mp: 116 °C. [R]21D: -206.9. [R]21578: -212.1. [R]21
:
546
-241.4. [R]21436: -382.7. [R]21365: -441.3 (c ) 0.98). 1H NMR
(250 MHz, CDCl3): δ 0.82 (d, J ) 6.9, 3H), 0.92 (d, J ) 7.6,
3H), 0.94 (d, J ) 6.9, 3H), 0.79-1.07 (m, 3H), 1.21-1.47 (m,
2H), 1.58-1.72 (m, 2H), 2.07-2.17 (m, 2H), 2.76-2.91 (m, 2H),
2.85 (s, 3H), 3.21 (m, 1H), 3.57 (td, J ) 10.7, 4.2, 3H), 3.84 (d,
J ) 6.9, 1H), 5.49 (d, J ) 1.5, 1H), 6.68 (d, J ) 8.4, 1H), 6.82
(td, J ) 7.2, 1.1, 1H), 7.17 (td, J ) 8.4, 1.1, 1H), 7.46 (d, J )
7.2, 1H). 13C NMR (62 MHz, CDCl3): δ 15.7, 20.8, 22.2, 23.2,
25.5, 31.3, 34.3, 39.4, 39.9, 40.4, 41.1, 47.7, 49.9, 77.2, 101.5,
112.0, 116.9, 118.4, 128.3, 130.5, 146.8, 175.5. IR (KBr): ν
2950, 2920, 1765, 1505, 1310, 1140, 970, 930, 750. MS m/z
(relative intensity): 357 (M+, 70), 313 (32), 254 (7), 174 (100),
157 (19), 146 (92), 144 (89). HRMS Calcd for C22H31NO3:
357.2296. Found: 357.2304. Anal. Calcd for C22H31NO3: C,
73.90; H, 8.99; N, 3.92. Found: C, 73.62; H, 8.99; N, 3.80.
Tetr ah ydr oqu in olin e Der ivative 22a. Yield: 8 mg (1.7%).
[R]21D: -52.4. [R]21578: -60.7. [R]21546: -132.9. [R]21436: -53.5.
[R]21365: -114.6 (c ) 0.42). 1H NMR (500 MHz, CDCl3): δ 0.71
(d, J ) 6.9, 3H), 0.82 (d, J ) 7.6, 3H), 0.89 (d, J ) 6.9, 3H),
0.79-1.07 (m,3H), 1.18-1.39 (m, 2H), 1.52-1.65 (m, 2H),
2.01-2.14 (m, 2H), 2.81-2.94 (m, 2H), 2.83 (s, 3H), 3.21 (dd,
J ) 12.0, 4.7, 1H), 3.56 (td, J ) 10.7, 4.2, 3H), 3.64 (d, J )
7.1, 1H), 5.80 (d, J ) 4.4, 1H), 6.61 (d, J ) 8.0, 1H), 6.73 (td,
J ) 7.4, 1.0, 1H), 7.11 (td, J ) 8.5, 1.4, 1H), 7.33 (d, J ) 7.4,
1H). 13C NMR (126 MHz, CDCl3): δ 15.9, 20.9, 22.2, 23.2, 25.6,
31.4,34.3, 38.0, 39.6, 39.8, 43.1, 47.4, 47.8, 78.6, 100.2, 111.8,
116.3, 117.8, 128.5, 130.7, 146.9, 173.9. IR (KBr): ν 2950, 2920,
1765, 1505, 1310, 1140, 970, 930, 750. MS m/z (relative
intensity): 357 (M+, 100), 313 (34), 254 (7), 174 (100), 157 (25),
146 (94), 144 (100). Anal. Calcd for C22H31NO3: C, 73.90; H,
8.99; N, 3.92. Found: C, 73.66; H, 8.96; N, 3.78.
Qu in olizid in e Der iva tive 6b. Yield: 196 mg (13%). Mp:
119 °C. [R]21D: -117.3. [R]21578: -120.9. [R]21546: -136.5. [R]21436:-
1
177.3. [R]21365: -231.1 (c ) 1.00). H NMR (250 MHz, CDCl3):
δ 0.75 (d, J ) 6.9, 3H), 0.80 (d, J ) 6.9, 3H), 0.83 (s, 3H), 0.86
(d, J ) 6.2, 3H), 0.87 (d, J ) 7.6, 3H), 0.58-1.01 (m, 3H), 1.09
(s, 3H), 1.08-1.42 (m, 4H), 1.45-1.82 (m, 5H), 1.87-2.17 (m,
2H), 2.42-2.70 (m, 3H), 2.80 (m, 1H), 2.87 (m, 1H), 3.42 (td,
J ) 10.7, 4.2, 1H), 5.18 (s, 1H).13C NMR (62 MHz, CDCl3): δ
15.4, 15.8, 18.4, 18.9, 20.7, 22.1, 22.9, 23.1, 23.8, 25.3, 31.1,
34.1, 39.8, 40.7, 41.7, 47.5, 47.7, 49.7, 54.8, 58.2, 76.0, 101.1,
179.1. IR (KBr): ν 2970, 2920, 1775, 1455, 1355, 1110, 955.
MS m/z (relative intensity): 377 (M+, 3), 362 (100), 318 (23),
224 (23), 194 (16), 112 (31). Anal. Calcd for C23H39NO3: C,
73.10; H, 10.34; N, 3.71. Found: C, 73.02; H, 10.12; N, 3.58.
Aza a zu len e Der iva tive 8. Yield: 481 mg (32%). Mp: 111
°C. [R]21D: -67.4. [R]21578: -69.8. [R]21546: -78.6. [R]21436: -123.2.
1
[R]21365: -129.3 (c ) 1.00). H NMR (250 MHz, C6D6): δ 0.48
(m, 1H), 0.69 (s, 3H), 0.83 (d, J ) 6.9, 3H), 0.95 (d, J ) 6.9,
3H), 0.98 (d, J ) 7.6, 3H), 0.68-1.02 (m, 2H), 1.20 (s, 3H),
1.20-1.68 (m, 8H), 2.10 (m, 1H), 2.25 (dd, J ) 7.2, 5.0, 1H),
2.36 (dsept, J ) 6.7, 2.3, 1H), 2.32 (m, 1H), 2.79 (m, 1H), 3.02
(m, 1H), 3.32 (dd, J ) 9.2,7.2, 1H), 3.51 (td, J ) 10.7, 4.2, 1H),
5.27 (d, J ) 11.0, 1H), 5.36 (dd, J ) 11.0, 9.2, 1H), 5.59 (s,
1H). 13C NMR (62 MHz, C6D6): δ 15.4, 17.2, 20.9, 22.2, 22.9,
25.4, 26.1, 26.7, 28.6, 31.3, 34.3, 39.7, 39.9, 46.5, 47.8, 52.1,
55.6, 60.4, 75.8, 99.2, 116.9, 144.1, 176.9. IR (KBr): ν 2960,
2920, 1795, 1465, 1090, 930. MS m/z (relative intensity): 375
(M+, 17), 360 (100), 316 (43), 236 (82), 220 (23), 178 (51), 148
(82), 124 (61). Anal. Calcd for C23H37NO3: C, 73.56; H, 9.93;
N, 3.73. Found: C, 73.32; H, 9.76; N, 3.50.
Aza a zu len e Der iva tive 9. Yield: 436 mg (29%). Mp: 98
°C. [R]21D: -82.0. [R]21578: -84.0. [R]21546: -95.0. [R]21436: -142.4.
[R]21365: -141.7 (c ) 1.02). 1H NMR (250 MHz, CDCl3): δ 0.72
(d, J ) 6.9, 3H), 0.80 (d, J ) 7.6, 3H), 0.87 (d, J ) 6.9, 3H),
La cton e 23. Yield: 55 mg (18%). Mp: 58 °C. [R]21D: -141.3.
[R]21578: -146.0. [R]21546: -166.9. [R]21436: -276.4. [R]21365: -278.0
(c ) 0.86). 1H NMR (250 MHz, CDCl3): δ 0.78 (d, J ) 7.3,
3H), 0.88 (d, J ) 7.3, 3H), 0.93 (d, J ) 6.5, 3H), 0.65-1.12 (m,

Tandem Reactions of Unsaturated Tertiary Amines
J . Org. Chem., Vol. 65, No. 25, 2000 8701
3H), 1.17-1.48 (m, 2H), 1.58-1.72 (m, 2H), 2.00-2.17 (m, 3H),
2.28 (m, 1H), 2.41 (ddd, J ) 18.1, 9.5, 3.4, 1H), 2.65 (m, 1H),
3.52 (td, J ) 10.7, 4.2, 1H), 5.71 (dd, J ) 5.3, 1.9, 1H). 13C
NMR (62 MHz, CDCl3): δ 15.6, 20.8, 22.2, 23.1, 25.5, 27.0,
29.1, 31.3, 34.3, 39.8, 47.8, 76.5, 100.3, 170.8. IR (KBr): ν 2950,
2925, 2870, 1790, 1460, 1360, 1155, 975, 950. MS (NH3) m/z
(relative intensity): 258 (M+ + 18, 85), 241 (M+ + 1, 100), 223
(24), 178 (10), 156 (92), 150 (35), 139 (98), 120 (50). Anal. Calcd
for C14H24O3: C, 69.95; H, 10.07. Found: C, 69.71; H, 9.79.
described for 19a . The degree of deuteration (Scheme 8) was
determined by integration of the 1H NMR spectra.
Tetr a h yd r oqu in olin e Der iva tive 21a ′. Yield: 158 mg
(35%). Mp: 116 °C. [R]21D: -197.4. [R]21578: -203.5. [R]21
:
546
-229.9. [R]21436: -363.9. [R]21365: -439.6 (c ) 0.94). 1H NMR
(250 MHz, CDCl3): δ 0.82 (d, J ) 6.9, 3H), 0.92 (d, J ) 7.6,
3H), 0.94 (d, J ) 6.9, 3H), 0.79-1.07 (m, 3H), 1.21-1.47 (m,
2H), 1.58-1.72 (m, 2H), 2.07-2.17 (m, 2H), 2.76-2.91 (m, 2H),
2.87 (s, 3H), 3.21 (dd, J ) 16.9, 9.2, 1H), 3.57 (td, J ) 10.7,
4.2, 3H), 3.87 (d, J ) 6.9, 1H), 5.49 (d, J ) 1.5, 1H), 7.19 (s,
1H), 7.48 (s, 1H). 13C NMR (62 MHz, CDCl3): δ 15.7, 20.8,
22.2, 23.2, 25.5, 31.3, 34.3, 39.4, 39.9, 40.4, 41.1, 47.7, 49.9,
77.2, 101.5, 112.0 (t, J ) 23.2), 116.9, 118.4 (t, J ) 23.0), 128.3,
130.5, 146.8, 175.5. IR (KBr): ν 2950, 2920, 2865, 1770, 1595,
1490, 1450, 1315, 1150, 1135, 970, 930. MS m/z (relative
intensity): 359 (M+, 35), 315 (17), 176 (100), 159 (13), 148 (91),
142 (71). Anal. Calcd for C22H29D2NO3: C, 73.49; H/D, 9.25;
N, 3.91. Found: C, 73.58; H/D, 9.25; N, 4.02.
Bisla cton e 24. Yield: 42 mg (7%). [R]21D: -195.4. [R]21
:
578
-205.4. [R]21546: -233.5. [R]21436: -388.0. [R]21365: -579.8 (c )
0.84). 1H NMR (250 MHz, CDCl3): δ 0.78 (d, J ) 7.3, 6H),
0.88 (d, J ) 7.3, 6H), 0.96 (d, J ) 6.5, 6H), 0.72-1.12 (m, 6H),
1.21-1.55 (m, 4H), 1.62-1.83 (m, 4H), 2.04-2.27 (m, 6H), 2.50
(m, 2H), 2.81 (dd, J ) 17.8, 8.5, 2H), 3.56 (td, J ) 10.7, 4.2,
2H), 5.53 (d, J ) 2.3, 2H). 13C NMR (62 MHz, CDCl3): δ 15.8,
20.8, 22.3, 23.1, 25.5, 31.4, 32.1, 34.3, 39.7, 43.4, 47.8, 77.0,
102.0, 173.7. IR (KBr): ν 2955, 2925, 2870, 1785, 1510, 1345,
1165, 945. MS (NH3) m/z (relative intensity): 478 (M+, 54),
373 (26), 335 (15), 229 (46), 216 (100), 139 (84). Anal. Calcd
for C28H46O6: C, 70.54; H, 9.31. Found: C, 70.30; H, 9.19.
Isotop ic La belin g Exp er im en ts. P r ep a r a tion of N,N-
Dim eth yl-2,4,6-tr id eu ter ioa n ilin e 19a ′.29 N,N-Dimethyl-
2,4,6-tribromoaniline30 was synthesized according to the lit-
erature.31 The reduction was also carried out according to a
literature procedure.32 Under an argon atmosphere, sodium
(5 g, 218 mmol) was added slowly to mercury (100 g, 500
mmol). After the mixture cooled to room temperature, deuterio-
methanol (40 mL) was added. The mixture was then heated
to reflux until the complete fusion of the amalgam. A solution
of N,N-dimethyl-2,4,6-tribromoaniline (7.15 g, 20 mmol) in
deuteriomethanol (10 mL) was added, and the resulting
mixture was heated under reflux for 6 h. Water (100 mL) was
added, and the mixture was extracted two times with ether.
The organic phase was washed with brine and dried over
MgSO4. After evaporation, the residue was distilled. Yield:
Tetr a h yd r oqu in olin e Der iva tive 21a ′′. Yield: 160 mg
(35%). Mp: 114 °C. [R]21D: -156.2. [R]21578: -160.0. [R]21
:
546
-180.6. [R]21436: -297.9. [R]21365: -381.1 (c ) 1.00). 1H NMR
(250 MHz, CDCl3): δ 0.82 (d, J ) 6.9, 3H), 0.92 (d, J ) 7.6,
3H), 0.94 (d, J ) 6.9, 3H), 0.79-1.07 (m, 3H), 1.21-1.47 (m,
2H), 1.58-1.72 (m, 2H), 2.07-2.17 (m, 2H), 2.86 (dd, J ) 8.0,
2.3, 1H, H4), 3.57 (td, J ) 10.7, 4.2, 3H), 3.87 (d, J ) 8.0, 1H),
5.49 (d, J ) 2.3, 1H), 6.68 (dd, J ) 8.4, 1.1, 1H), 6.82 (td, J )
7.2, 1.1, 1H), 7.17 (td, J ) 8.4, 1.1, 1H), 7.46 (d, J ) 7.2, 1H).
13C NMR (62 MHz, C6D6): δ 16.0, 21.2, 22.4, 23.4, 25.9, 31.4,
34.6, 38.3 (sept, J ) 21.5), 40.3, 40.5, 41.3, 48.2, 48.9 (qt, J )
22.3), 77.0, 101.2, 112.3, 113.0, 118.8, 129.5, 131.2, 147.2,
174.9. IR (KBr): ν 2950, 2925, 2820, 1770, 1580, 1490, 1455,
1325, 1155, 1140. MS m/z (relative intensity): 362 (M+, 38),
318 (23), 181 (100), 161 (19), 151 (93), 147 (73). Anal. Calcd
for C22H26D5NO3: C, 72.82; H/D, 9.93; N, 3.86. Found: C,
72.49; H/D, 9.64; N, 3.71.
P r ep a r a tion of Ter tia r y An ilin e Der iva tives 19d a n d
19f.31 A solution of the 2,3-dimethylaniline or 5,6,7,8-tetrahydro-
naphthalen-1-ylamine (27 mmol) and sodium borohydride (6
g, 159 mmol) in THF was added dropwise to a solution of
formaline (37%, 8.3 mL, 110 mmol) and sulfuric acid (7 mL,
128 mmol) in 50 mL of THF. The mixture was rapidly stirred
for 1 h. Water (50 mL) was then added dropwise, and solid
KOH (21.5 g) was added to adjust the pH at about 10. After
filtration the solution was extracted with ether (2 × 50 mL).
The organic phases were washed with brine and dried with
MgSO4. After evaporation of the solvent, the residue was
distilled.
1
2.06 g (83%). Bp20: 86 °C, H NMR (250 MHz, CDCl3): δ 3.01
(s, 6H) 7.32 (s, 2H). 13C NMR (62 MHz, CDCl3): δ 40.3, 112.2,
116.2 (t, J ) 23.9), 128.6 (t, J ) 23.9), 150.3. IR (film): ν 2935,
2860, 2795, 1590, 1490, 1430. MS m/z (relative intensity): 124
(M+, 68), 123 (100).
P r ep a r a t ion of N,N-Bis(t r id eu t er iom et h yl)a n ilin e
19a ′′.33,26d Trideuterioiodomethane was prepared according to
a literature procedure.34 The N-alkylation was carried out
according to a modified literature procedure.35 Trideuterio-
iodomethan (62.3 g, 430 mmol) was added dropwise to a
mixture of aniline (15 g, 161 mmol), Na2CO3 (18 g, 217 mmol),
and ethanol (25 mL). The reaction mixture was heated under
reflux for 10 h. After the mixture cooled to room temperature
an aqueous solution of dimethylamine (140 mL, 40%) was
added. The resulting mixture was heated on a water bath for
3 h. NaOH (10 mL, 2 N) was then added, and the solution
was extracted with ether. The organic phase was dried with
MgSO4. The ether was evaporated and the residue was
distilled. Yield: 12.2 g (60%). Bp10: 78 °C. 1H NMR (250 MHz,
CDCl3): δ 6.83 (m, 3H), 7.35 (s, 2H). 13C NMR (62 MHz,
CDCl3): δ 39.6 (sep, J ) 20.5), 112.5, 116.5, 129.0, 150.6. IR
(film): ν 3060, 2055, 1605, 1505, 1340. MS m/z (relative
intensity): 127 (M+, 63), 125 (100).
An ilin e d er iva tive 19d .31 Yield: 3.27 g (81%). Bp20: 97
1
°C. H NMR (250 MHz, CDCl3): δ 2.49 (s, 3H), 2.50 (s, 3H),
2.79 (s, 6H), 7.00 (d, J ) 7.3, 1H), 7.05 (d, J ) 7.3, 1H), 7.18
(t, J ) 7.3, 1H). 13C NMR (62 MHz, CDCl3): δ 14.2, 20.5, 44.6,
116.1, 124.5, 125.6, 130.9, 137.8, 152.9.
An ilin e Der iva tive 19f.36 Yield: 4.08 g (86%). Bp20: 138
1
°C. H NMR (250 MHz, CDCl3): δ 1.87 (m, 4H), 2.73 (s, 6H),
2.86 (m, 4H), 6.88 (d, J ) 8.1, 1H), 6.96 (d, J ) 8.1, 1H), 7.14
(t, J ) 8.1, 1H). 13C NMR (62 MHz, CDCl3): δ 23.0, 23.2, 25.4,
29.7, 44.4, 115.7, 124.0, 125.6, 132.2, 138.1,154.3.
Rea ction of (5R)-5-Men th yloxy-2-[5H]-fu r a n on e 1 w ith
N,N-Dim et h yla n ilin e 19a in t h e P r esen ce of Ket on es.
(Table 2, Schemes 12 and 13) A solution of (5R)-5-menthyloxy-
2-[5H]-furanone 1 (200 mg, 0.84 mmol), N,N-dimethylaniline
19a (1.21 g, 20 mmol), bis(dimethylamino)benzophenone 20,
and acetone or cyclopentanone in acetonitrile (15 mL) or
acetone was irradiated according to Table 2. For the reactions
described in Schemes 13 and 14, acetone (1 mL) was added to
the reaction mixture. The solution was evaporated, and the
residue was subjected to flash chromatography (ethyl acetate/
petroleum ether 1/5). The diastereomeric excess was then
determined by NMR spectroscopy (integration of the signal of
H5 in the 1H NMR spectrum). After recrystallization from
petroleum ether, the major isomers were completely character-
ized.
Rea ction of (5R)-5-Men th yloxy-2-[5H]-fu r a n on e 1 w ith
Deu ter a ted N,N-Dim eth yla n ilin e Der iva tives 19a ′, 19a ′′.
The reactions were carried out under the same conditions as
(29) Prenner, G. H.; Polson, J . M.; Daleman, S. I.; Reid, K. Can. J .
Chem. 1993, 71, 417-426.
(30) (a) Clarke, H. T.; Gillespie, H. B.; Weisshaus, S. Z. J . Am. Chem.
Soc. 1933, 55, 4571-4587. (b) Few, A. V.; Smith, J . W. J . Chem. Soc.
1949, 2663-2668.
(31) Giumanini, A.; Chiavari, G.; Musiani, M. M.; Rossi, P. Synthesis
1980, 743-746.
(32) Miura, Y.; Oka, H.; Yamano, E.; Morita, M. J . Org. Chem. 1997,
62, 1188-1190.
(33) Dinnocenzo, J . P.; Karki, S. B.; J ones, J . P. J . Am. Chem. Soc.
1993, 115, 7111-7116
(34) Pyun, H.-J .; Coates, R. M.; Wagschal, K. C.; McGeady, P.;
Coteau, R. B. J . Org. Chem. 1993, 58, 3998-4009.
(35) Thesing, J . Chem. Ber. 1954, 87, 962-699.
(36) Kloubek, J . Collect. Czech. Chem. Commun. 1966, 31, 3536-
3546.

8702 J . Org. Chem., Vol. 65, No. 25, 2000
Bertrand et al.
Tetr a h yd r oqu in olin e Der iva tive 21b. Yield: 232 mg
-178.0. [R]21436: -277.9. [R]21365: -357.7 (c ) 1.00). 1H NMR
(250 MHz, CDCl3): δ 0.81 (d, J ) 6.9, 3H), 0.91 (d, J ) 7.6,
3H), 0.95 (d, J ) 6.9, 3H), 0.81-1.11 (m, 3H), 1.21-1.48 (m,
2H), 1.60-1.74 (m, 2H), 2.04-2.20 (m, 2H), 2.47 (s, 3H), 2.87
(s, 3H), 2.67-3.00 (m, 2H), 3.21 (m, 1H), 3.57 (td, J ) 10.7,
4.2, 1H), 3.83 (d, J ) 8.2, 1H), 5.51 (d, J ) 1.9, 1H), 6.52 (s,
1H), 6.68 (d, J ) 8.0, 1H), 7.47 (d, J ) 8.0, 1H). 13C NMR (62
MHz, CDCl3): δ 15.7, 20.9, 21.7, 22.2, 23.1, 25.5, 31.4, 34.3,
39.5, 39.9, 40.2, 41.1, 47.7, 50.0, 77.2,101.6, 109.5, 112.8, 119.4,
130.4, 138.2, 147.1, 176.3. IR (KBr): ν 2945, 2870, 1775, 1640,
1455, 1110, 930. MS m/z (relative intensity): 371 (M+, 70),
(62%). Mp: 126 °C. [R]21D: -103.2. [R]21578: -107.4. [R]21
:
546
-123.2. [R]21436: -197.9. [R]21365: -266.3 (c ) 0.96). 1H NMR
(250 MHz, CDCl3): δ 0.82 (d, J ) 6.9, 3H), 0.93 (d, J ) 7.6,
3H), 0.95 (d, J ) 6.9, 3H), 0.79-1.07 (m, 3H), 1.19-1.46 (m,
2H), 1.58-1.74 (m, 2H), 2.04-2.15 (m, 2H), 2.28 (s, 3H), 2.76
(s, 3H), 2.80-2.95 (m, 2H), 3.17 (m, 1H), 3.61 (td, J ) 10.7,
4.2, 1H), 3.88 (d, J ) 7.6, 1H), 5.53 (s, 1H), 7.08 (d, J ) 7.6,
1H), 7.17 (t, J ) 8.2, 1H), 7.43 (d, J ) 7.6, 1H). 13C NMR (62
MHz, CDCl3): δ 15.7, 18.0, 20.9, 22.2, 23.3, 25.7, 31.4, 33.9,
34.4, 39.6,40.2, 42.0, 47.9, 50.8, 76.5, 100.3, 121.8, 122.9, 126.7,
128.7, 130.2, 146.0,175.9. IR (KBr): ν 2960, 2870, 2795, 1795,
1590, 1480, 1365, 1115, 930, 765. MS m/z (relative intensity):
372 (M+ + 1, 47), 327 (15), 234 (32), 188 (16), 158 (3), 135 (18),
134 (100). Anal. Calcd for C23H33NO3: C, 74.34; H, 8.96; N,
3.77. Found: C, 74.13; H, 8.93; N, 3.54.
327 (23), 188 (100), 160 (84), 158 (76). Anal. Calcd for C23H33
-
NO3: C, 74.34; H, 8.96; N, 3.77. Found: C, 74.08; H, 9.07; N,
3.83.
Tetr a h yd r oqu in olin e Der iva tive 22′e. 1H NMR (250
MHz, CDCl3): δ 5.93 (d, J ) 4.5, 1H).
Tetr a h yd r oqu in olin e Der iva tive 22b. 1H NMR (250
MHz, CDCl3): δ 5.96 (d, J ) 4.6, 1H).
Aza ster eoid 21f. Yield: 230 mg (56%). Mp: 158 °C. [R]21
:
D
-159.0. [R]21578: -163.6. [R]21546: -185.4. [R]21436: -283.5.
[R]21365: -358.9 (c ) 1.02). 1H NMR (250 MHz, CDCl3): δ 0.83
(d, J ) 7.6, 3H), 0.92 (d, J ) 6.9, 3H), 0.96 (d, J ) 6.9, 3H),
0.80-1.07 (m, 3H), 1.21-2.03 (m, 8H), 2.04-2.23 (m, 1H),
2.37-2.53 (m, 1H), 2.68 (s, 3H), 2.72-2.82 (m, 3H), 2.83-2.96
(m, 3H), 3.27 (dd, J ) 14.2, 4.2, 1H), 3.61 (td, J ) 10.7, 4.2,
1H), 3.85 (d, J ) 7.2, 1H), 5.34 (s, 1H), 6.88 (d, J ) 7.6, 1H),
7.38 (d, J ) 7.6, 1H). 13C NMR (62 MHz, CDCl3): δ 15.7, 20.9,
22.2, 23.0, 23.1, 23.2, 25.4, 25.7, 29.5, 31.4, 33.7, 34.4, 39.6,
39.8, 41.7, 47.9, 51.0, 77.0, 100.4, 118.8, 124.4, 127.8, 131.6,
137.4, 147.9, 176.2. IR (KBr): ν 2950, 2860, 1770, 1455, 1365,
1105, 915. MS m/z (relative intensity): 411 (M+, 18), 367 (14),
228 (16), 188 (100). Anal. Calcd for C26H37NO3: C, 75.86; H,
9.67; N, 3.40. Found: C, 75.75; H, 9.57; N, 3.46.
Tetr a h yd r oqu in olin e Der iva tive 21c. Yield: 300 mg
(81%). Mp: 142 °C. [R]21D: -182.3. [R]21578: -186.1. [R]21
:
546
-210.8. [R]21436: -343.1. [R]21365: -438.4 (c ) 1.00). 1H NMR
(250 MHz, CDCl3): δ 0.82 (d, J ) 6.9, 3H), 0.92 (d, J ) 7.6,
3H), 0.94 (d, J ) 6.9, 3H), 0.79-1.07 (m, 3H), 1.21-1.47 (m,
2H), 1.58-1.72 (m, 2H), 2.07-2.17 (m, 2H), 2.26 (s, 3H), 2.76-
2.91 (m, 2H), 2.83 (s, 3H), 3.17 (m, 1H), 3.57 (td, J ) 10.7, 4.2,
1H), 3.82 (d, J ) 7.6, 1H), 5.51 (d, J ) 1.5, 1H), 6.60 (d, J )
8.4, 1H), 6.98 (dd, J ) 7.6, 1.2, 1H), 7.29 (d, J ) 1.1, 1H). 13C
NMR (62 MHz, CDCl3): δ 15.5, 20.0, 20.6, 22.0, 23.0, 25.3,
31.1, 34.1, 39.4, 39.7, 40.3, 41.2, 47.5, 50.0, 76.8, 101.4, 112.0,
116.7, 127.5, 128.8, 130.7, 144.5, 175.4. IR (KBr): ν 2860, 1770,
1515, 1365, 1280, 1090, 925, 800. MS m/z (relative intensity):
371 (M+, 100), 327 (60), 189 (53), 188 (97), 171 (35), 161 (32),
160 (97), 158 (100), 144 (32). Anal. Calcd for C23H33NO3: C,
74.34; H, 8.96; N, 3.77. Found: C, 74.94; H, 8.85; N, 3.61.
Tetr a h yd r oqu in olin e Der iva tive 22c. 1H NMR (250
MHz, CDCl3): δ 5.83 (d, J ) 4.6, 1H).
1
Aza ster oid 22f. H NMR (250 MHz, CDCl3): δ 5.83 (d, J
) 4.5, 1H).
Tetr a h yd r oqu in olin e Der iva tive 21g. Yield: 138 mg
(36%). Mp: 133 °C. [R]21D: -128.9. [R]21578: -133.3. [R]21
:
546
-150.0. [R]21436: -232.8. [R]21365: -276.1 (c ) 0.92). 1H NMR
(250 MHz, CDCl3): δ 0.75 (d, J ) 6.9, 3H), 0.80 (d, J ) 6.5,
3H), 0.83 (d, J ) 6.9, 3H), 0.86 (d, J ) 7.6, 3H), 0.72-0.95 (m,
3H), 0.97-1.26 (m, 2H), 1.13 (t, J ) 7.2, 3H), 1.54-1.67 (m,
2H), 2.02-2.16 (m, 2H), 2.81 (dd, J ) 8.4, 5.0, 1H), 3.06 (dq,
J ) 14.5, 7.2, 1H), 3.21-3.58 (m, 3H), 3.74 (d, J ) 8.4, 1H),
5.44 (s, 1H), 6.61 (d, J ) 8.9, 1H), 6.71 (t, J ) 7.4, 1H), 7.08 (t,
J ) 9.0, 1H), 7.52 (d, J ) 7.6, 1H). 13C NMR (62 MHz, CDCl3):
δ 13.0, 13.1, 15.7, 20.9, 22.2, 23.1, 25.6, 31.3, 34.3, 37.6, 39.7,
43.7, 44.3, 47.7, 50.8, 76.6, 100.3, 112.4, 115.7, 117.3, 128.3,
130.5, 143.5, 176.1. IR (KBr): ν 2940, 2870, 1780, 1600, 1500,
1455, 1360, 1265, 1110, 930. MS m/z (relative intensity): 385
(M+, 74), 341 (23), 326 (18), 202 (100), 188 (45), 174 (34), 158
(90), 144 (15), 130 (31). Anal. Calcd for C24H35NO3: C, 74.75;
H, 9.16; N, 3.64. Found: C, 74.84; H, 8.89; N, 3.76.
Tetr a h yd r oqu in olin e Der iva tive 21d . Yield: 258 mg
(67%). Mp: 158 °C. [R]21D: -104.0. [R]21578: -104.6. [R]21
:
546
-120.0. [R]21436: -182.6. [R]21365: -231.2 (c ) 1.00). 1H NMR
(250 MHz, CDCl3): δ 0.82 (d, J ) 6.9, 3H), 0.91 (d, J ) 7.6,
3H), 0.96 (d; J ) 6.9, 3H), 0.82-1.10 (m, 3H), 1.22-1.51 (m,
2H), 1.61-1.75 (m, 2H), 2.06-2.20 (m, 2H), 2.20 (s, 3H), 2.26
(s, 3H), 2.67 (s, 3H), 2.76 (dd, J ) 12.2, 6.5, 1H), 2.90 (ddd, J
) 7.2, 6.5, 4.2, 1H), 3.30 (dd, J ) 12.2, 4.2, 1H), 3.60 (td, J )
10.7, 4.2, 1H), 3.81 (d, J ) 7.2, 1H), 5.37 (s, 1H), 6.95 (d, J )
7.6, 1H), 7.38 (d, J ) 7.6, 1H). 13C NMR (62 MHz, CDCl3): δ
14.2, 15.6, 20.4, 20.9, 22.5, 23.1, 25.6, 31.4, 33.4, 34.3, 39.7,
39.9, 42.5, 47.8, 50.7, 76.4, 100.3, 119.4, 125.0, 127.9, 130.5,
137.1, 146.1, 176.2. IR (KBr): ν 2920, 2860, 1780, 1455, 1255,
1105, 1030, 915. MS m/z (relative intensity): 385 (M+, 69),
341 (58), 230 (14), 202 (100), 172 (79), 158 (32). Anal. Calcd
for C24H35NO3: C, 74.75; H, 9.16; N, 3.63. Found: C, 74.76;
H, 9.11; N, 3.45.
Tetr a h yd r oqu in olin e Der iva tive 26g. Yield: 112 mg
(29%). Mp: 116 °C. [R]21D: -110.9. [R]21578: -107.3. [R]21
:
546
-115.5. [R]21436: -116.4. [R]21365: -179.1 (c ) 1.00). 1H NMR
(250 MHz, CDCl3): δ 0.81 (d, J ) 6.9, 3H), 0.91 (d, J ) 7.6,
3H), 0.93 (d, J ) 6.9, 3H), 0.79-1.10 (m, 3H), 1.08 (d, J ) 6.5,
3H), 1.17-1.46 (m, 2H), 1.23 (t, J ) 7.1, 3H), 1.50-1.71 (m,
2H), 2.04 (m, 1H), 2.11 (dst, J ) 6.9, 2.5, 1H), 2.51 (ddd, J )
9.2, 6.5, 2.7, 1H), 3.12 (dq, J ) 14.5, 7.2, 1H), 3.42 (m, 2H),
3.51 (td, J ) 10.7, 4.2, 1H), 3.84 (d, J ) 9.2, 1H), 5.61 (d, J )
6.5, 1H), 6.63 (d, J ) 8.4, 1H), 6.71 (td, J ) 7.2, 0.8, 1H), 7.14
(td, J ) 7.2, 0.8, 1H), 7.47 (dd, J ) 7.2, 0.8, 1H). 13C NMR (62
MHz, CDCl3): δ 13.4, 15.8, 16.5, 20.9, 22.2, 23.1, 25.4, 31.3,
34.2, 40.3, 40.4, 43.8, 47.8, 48.7, 50.2, 78.6, 103.5, 112.1, 115.2,
117.3, 128.7, 129.5, 143.1, 174.4. IR (KBr): ν 2935, 2855, 1765,
1600, 1500, 1330, 1135, 930. MS m/z (relative intensity): 385
(M+, 40), 341 (19), 326 (51), 230 (12), 202 (100), 188 (23), 174
(28), 158 (68), 130 (18). Anal. Calcd for C24H35NO3: C, 74.75;
H, 9.16; N, 3.64. Found: C, 74.82; H, 8.84; N, 3.79.
Tetr a h yd r oqu in olin e Der iva tive 22d . 1H NMR (250
MHz, CDCl3): δ 5.84 (d, J ) 4.5, 1H).
Tetr a h yd r oqu in olin e Der iva tive 21e. Yield: 192 mg
(52%). Mp: 123 °C. [R]21D: -206.6. [R]21578: -218.0. [R]21
:
546
-249.2. [R]21436: -418.0. [R]21365: -596.4 (c ) 0.24). 1H NMR
(250 MHz, CDCl3): δ 0.83 (d, J ) 6.9, 3H), 0.89 (d, J ) 7.6,
3H), 0.95 (d, J ) 6.9, 3H), 0.80-1.07 (m, 3H), 1.19-1.45 (m,
2H), 1.58-1.72 (m, 2H), 2.07-2.17 (m, 2H), 2.43 (s, 3H), 2.84
(s, 3H), 2.74-2.96 (m, 2H), 3.18 (m, 1H), 3.60 (td, J ) 10.7,
4.2, 1H), 4.12 (d, J ) 7.6, 1H), 5.44 (s, 1H), 6.56 (d, J ) 8.0,
1H), 6.71 (d, J ) 8.0, 1H), 7.09 (t, J ) 8.0,1H). 13C NMR (62
MHz, CDCl3): δ 15.8, 19.9, 20.9, 22.2, 22.6, 25.9, 29.5, 34.3,
38.6, 39.8, 39.9, 40.9, 47.8, 50.9, 76.7, 101.9, 109.9, 116.3, 121.0,
128.0, 139.1, 154.7, 175.9. IR (KBr): ν 2950, 2365, 1785, 1610,
1485, 1095, 920. MS m/z (relative intensity): 371 (M+, 70),
327 (23), 188 (100), 160 (84), 158 (76). Anal. Calcd for C23H33
-
Ben zoin d olizid in e Der iva tive 21h . Yield: 150 mg (39%).
Mp: 130 °C. [R]21D: -115.2. [R]21578: -119.7. [R]21546: -135.0.
[R]21436: -211.5. [R]21365: -226.5 (c ) 1.00). 1H NMR (250 MHz,
CDCl3): δ 0.76 (d, J ) 6.9, 3H), 0.84 (d, J ) 6.9, 3H), 0.88 (d,
J ) 7.6, 3H), 0.70-1.00 (m, 3H), 1.03-1.38 (m, 2H), 1.53-
1.72 (m, 4H), 1.83-2.14 (m, 3H), 2.22 (dst, J ) 6.9, 2.7, 1H),
2.30 (dd, J ) 11.0, 7.2, 1H), 2.68 (ddd, J ) 11.0, 10.0, 5.7, 1H),
NO3: C, 74.34; H, 8.96; N, 3.77. Found: C, 74.11; H, 9.13; N,
3.86.
Tetr a h yd r oqu in olin e Der iva tive 22e. 1H NMR (250
MHz, CDCl3): δ 5.93 (d, J ) 4.6, 1H).
Tetr a h yd r oqu in olin e Der iva tive 21′e. Yield: 82 mg
(22%). Mp: 131 °C. [R]21D: -153.9. [R]21578: -157.9. [R]21
:
546

Tandem Reactions of Unsaturated Tertiary Amines
J . Org. Chem., Vol. 65, No. 25, 2000 8703
3.05 (ddd, J ) 14.8, 9.1, 4.6, 1H), 3.36 (dd, J ) 14.8, 8.8, 1H),
3.51 (td, J ) 10.7, 4.2, 1H), 3.80 (d, J ) 7.2, 1H), 5.47 (s, 1H),
6.45 (d, J ) 8.0, 1H), 6.69 (dd, J ) 7.6, 7.2, 1H), 7.08 (dd, J )
7.6, 7.2, 1H), 7.39 (d, J ) 7.2, 1H). 13C NMR (62 MHz, CDCl3):
δ 15.7, 20.9, 22.2, 22.7, 23.2 (C3′) 25.7, 30.8, 31.4, 34.3, 39.7,
40.0, 45.6, 46.6, 47.7, 55.9, 77.5, 100.3, 111.7, 115.5, 117.3,
128.3, 130.7, 144.3, 176.1. IR (KBr): ν 2955, 2855, 1775, 1460,
1260, 1095, 1035. MS m/z (relative intensity): 383 (M+, 63),
200 (100), 170 (81), 146 (60). Anal. Calcd for C24H33NO3: C,
75.14; H, 9.20; N, 3.65. Found: C, 74.99; H, 8.96; N, 3.56.
Ben zoin d olizid in e Der iva tive 26h . Yield: 122 mg (32%).
Mp: 124 °C. [R]21D: -109.9. [R]21578: -111.3. [R]21546: -117.2.
[R]21436: -104.0. [R]21365: +274.0 (c ) 1.00). 1H NMR (250 MHz,
CDCl3): δ 0.74 (d, J ) 6.9, 3H), 0.83 (d, J ) 6.9, 3H), 0.93 (d,
J ) 7.6, 3H), 0.69-0.97 (m, 3H), 1.10-1.34 (m, 2H), 1.51-
1.67 (m, 4H), 1.81-2.09 (m, 3H), 2.16 (dst, J ) 6.9, 2.7, 1H),
2.83-2.99 (m, 2H), 3.18 (ddd, J ) 11.8, 6.9, 3.4, 1H), 3.40-
3.55 (m, 2H), 3.89 (d, J ) 9.5, 1H), 5.63 (d, J ) 6.5, 1H), 6.48
(dd, J ) 8.4, 0.8, 1H), 6.68 (td, J ) 7.2-0.8, 1H), 7.07 (td, J )
8.4, 0.8, 1H), 7.42 (dd, J ) 7.6, 0.8, 1H). 13C NMR (62 MHz,
CDCl3): δ 15.9, 21.0, 22.3, 22.7, 23.1, 25.3, 27.3, 31.4, 34.3,
40.0, 43.7, 45.6, 47.1, 48.0, 55.8, 78.2, 101.0, 112.3, 116.8, 118.0,
128.4, 129.2, 146.1, 174.4. IR (KBr): ν 2920, 2845, 1770, 1605,
an aqueous KOH solution (10%, 50 mL), the mixture was
extracted with ether. The organic phase was washed with brine
and dried with MgSO4. After evaporation of the solvent, a
yellow oil was obtained that was dissolved in 20 mL of CH2Cl2
and filtered over silica. After evaporation, an uncolored oil was
1
obtained. Yield: 15.9 g (84%). H NMR (250 MHz, CDCl3): δ
2.15 (m, 4H), 2.22 (s, 6H), 2.26 (s, 3H), 3.15 (m, 4H), 6.82 (s,
2H). 13C NMR (62 MHz, CDCl3): δ 18.5, 20.7, 26.5, 50.1, 129.2,
134.4, 138.1, 142.7.
Rea ction of (5R)-5-Men th yloxy-2-[5H]-fu r a n on e 1 w ith
N-Mesitylp yr r olid in e 27. A solution of (5R)-5-menthyloxy-
2-[5H]-furanone 1 (120 mg, 0.5 mmol), N-mesitylpyrrolidine
27 (1.89 g, 10 mmol), and 4,4′-dimethoxybenzophenone (12 mg,
0.05 mmol) was irradiated at 350 nm for 7 min. After
evaporation of the excess of solvent and amine, the residue
was subjected to flash chromatography (eluent, ethyl acetate/
petroleum ether 1/2).
Am in e Ad d u ct 28. Yield: 132 mg (62%). [R]21D: -57.6.
[R]21578: -59.2. [R]21546: -63.7. [R]21436: -66.8. [R]21365: -67.4 (c
1
) 0.98). H NMR (250 MHz, CDCl3): δ 0.62 (d, J ) 6.9, 3H)
0.78 (d, J ) 7.6, 3H) 0.82 (d, J ) 6.9, 3H) 0.52-0.96 (m, 3H)
0.98-1.32 (m, 4H) 1.40-1.78 (m, 4H) 1.80-2.22 (m, 2H) 2.11
(s, 3H) 2.18 (s, 3H) 2.19 (s, 3H) 2.36 (dd, J ) 18.3, 8.0, 1H)
2.58 (dd, J ) 18.3, 8.7, 1H) 2.91 (ddd, J ) 15.8, 7.3, 6.9, 1H)
3.38 (m, 3H) 3.60 (dd, J ) 7.3, 6.1, 1H) 5.09 (s, 1H) 6.72 (s,
1H) 6.74 (s, 1H). 13C NMR (62 MHz, CDCl3): δ 15.3, 19.0, 19.2,
20.7, 20.8, 22.1, 24.5, 25.0, 25.4, 29.2, 30.4, 31.1, 34.2, 39.0,
47.3, 47.7, 52.5, 60.0, 75.4, 101.8, 129.3, 130.6, 134.8, 135.6,
135.8, 141.8, 176.4. IR (KBr): ν 2960, 2870, 1780, 1455, 1360,
1245, 1155, 940. MS m/z (relative intensity): 427 (M+, 7), 288
(11), 188 (100), 146 (5). Anal. Calcd for C27H41NO3: C, 75.82;
H, 9.67; N, 3.28. Found: C, 75.60; H, 9.39; N, 3.06.
1505, 1455, 1115, 955. MS m/z (relative intensity): 383 (M+•
70), 200 (21), 169 (33), 146 (100), 119 (16). Anal. Calcd for
24H33NO3: C, 75.14; H, 9.20; N, 3.65. Found: C, 74.93; H,
,
C
8.91; N, 3.59.
Ben zoqu in olizid in e Der iva tive 21i. Yield: 191 mg (48%).
Mp: 129 °C. [R]21D: -133.2. [R]21578: -137.5. [R]21546: -154.6.
[R]21436: -222.8. [R]21365: -256.1 (c ) 1.00). 1H NMR (250 MHz,
CDCl3): δ 0.81 (d, J ) 6.9, 3H), 0.91 (d, J ) 7.6, 3H), 0.95 (d,
J ) 6.9, 3H), 0.78-1.12 (m, 3H), 1.21-1.48 (m, 2H), 1.52-
1.92 (m, 9H), 2.18 (dst, J ) 6.9, 2.7, 1H), 2.61 (td, J ) 12.2,
3.0, 1H), 2.78 (ddd, J ) 9.5, 7.6, 4.6, 1H), 3.02-3.18 (m, 2H),
3.58 (td, J ) 10.7, 4.2, 1H), 3.88 (d, J ) 9.5, 1H), 5.80 (d, J )
4.6, 1H), 6.82 (dd, J ) 8.4, 7.6, 1H), 6.86 (d, J ) 8.4, 1H), 7.18
(td, J ) 8.4, 1.5, 1H), 7.42 (d, J ) 7.6, 1H). 13C NMR (62 MHz,
CDCl3): δ 15.8, 21.0, 22.3, 23.2, 24.0, 24.4, 25.4, 28.3, 31.4,
34.3, 39.9, 41.6, 45.9, 47.9, 48.4, 54.4, 77.8, 101.3, 113.5, 119.0,
127.1, 128.5, 130.1, 146.7, 175.0. IR (KBr): ν 2930, 2850, 1780,
1625, 1460, 1365, 1270, 1155, 945. MS m/z (relative inten-
sity): 397 (M+, 71), 353 (23), 214 (100), 186 (77), 149 (53), 129
(22), 120 (83). Anal. Calcd for C25H37NO3: C, 75.52; H, 8.88;
N, 3.52. Found: C, 75.41; H, 9.01; N, 3.47.
Am in e Ad d u ct 29. Yield: 34 mg (16%). [R]21D: -97.1.
[R]21578: -101.8. [R]21546: -118.2. [R]21436: -121.3. [R]21365: -133.2
(c ) 0.98). 1H NMR (250 MHz, CDCl3): δ 0.66 (d, J ) 6.9,
3H), 0.78 (d, J ) 7.6, 3H), 0.80 (d, J ) 6.9, 3H), 0.50-0.98 (m,
3H), 1.00-1.32 (m, 4H), 1.43-1.72 (m, 4H), 1.80-2.27 (m, 2H),
2.13 (s, 3H), 2.16 (s, 3H), 2.18 (s, 3H), 2.42 (dd, J ) 18.0, 7.2,
1H), 2.47 (dd, J ) 18.0, 9.3, 1H), 2.91 (ddd, J ) 16.0, 8.4, 7.2,
1H), 3.28 (m, 3H), 3.63 (ddd, J ) 8.4, 7.3, 4.2, 1H), 5.22 (d, J
) 4.2, 1H), 6.74 (s, 1H) 6.78 (s, 1H). 13C NMR (62 MHz,
CDCl3): δ 15.6, 18.6, 19.2, 20.6, 20.7, 22.1, 22.8, 25.0, 25.4,
29.2, 30.3, 30.8, 34.2, 36.2, 47.3, 48.8, 53.1, 57.9, 73.6, 98.6,
128.3, 130.4, 134.6, 136.8, 137.9, 142.3, 176.3. IR (KBr): ν
2955, 2865, 1785, 1450, 1375, 1245, 1145, 930. MS m/z (relative
intensity): 427 (M+, 7), 288 (7), 188 (100), 146 (8), 119 (8).
Anal. Calcd for C27H41NO3: C, 75.82; H, 9.67; N, 3.28. Found:
C, 75.63; H, 9.42; N, 3.01.
Ben zoqu in olizid in e Der iva tive 26i. Yield: 102 mg (26%).
Mp: 142 °C. [R]21D: -125.2. [R]21578: -127.0. [R]21546: -144.3.
[R]21436: -217.9. [R]21365: -239.9 (c ) 0.98). 1H NMR (250 MHz,
CDCl3): δ 0.82 (d, J ) 6.9, 3H), 0.92 (d, J ) 7.6, 3H), 0.95 (d,
J ) 6.9, 3H), 0.80-1.12 (m, 3H), 1.21-1.56 (m, 2H), 1.57-
1.76 (m, 6H), 1.78-1.95 (m, 3H), 2.15 (dst, J ) 6.9, 2.7, 1H),
2.52 (ddd, J ) 8.0, 3.4, 3.1, 1H), 2.69-2.82 (m, 2H), 3.57 (td,
J ) 10.7, 4.2, 1H), 3.82 (d, J ) 8.0, 1H), 3.96 (m 1H), 5.61 (d,
J ) 3.1, 1H), 6.82 (dd, J ) 8.0, 7.6, 1H), 6.87 (d, J ) 8.0, 1H),
7.18 (t, J ) 8.0, 1H), 7.39 (d, J ) 7.6, 1H). 13C NMR (62 MHz,
CDCl3): δ 15.7, 20.9, 22.2, 23.1, 23.7, 24.1, 25.7, 30.2, 31.4,
34.3, 39.4, 40.0, 46.8, 47.7, 48.1, 54.2, 77.7, 101.5, 113.2, 116.3,
118.4, 128.6, 130.4, 145.1, 175.4. IR (KBr): ν 2935, 2860, 1770,
1590, 1455, 1365, 1270, 1125,925. MS m/z (relative inten-
sity): 397 (M+, 78), 353 (44), 214 (100), 186 (93), 149 (45), 129
(48), 120 (96). Anal. Calcd for C25H37NO3: C, 75.52; H, 8.88;
N, 3.52. Found: C, 75.46; H, 9.07; N, 3.67.
Ack n ow led gm en t. S. Bertrand thanks the Re´gion
Champagne-Ardenne for a fellowship. The authors
thank Dr. Karen Ple´ (UPRESA 6013, CNRS) for some
language corrections of the manuscript.
Su p p or tin g In for m a tion Ava ila ble: Table with NMR
data for the determination of structures 6a ,b by comparison
with corresponding data of 5a ,b. Tables with energies and XYZ
coordinates. This material is available free of charge via the
Internet at http://pubs.acs.org.
P r ep a r a tion of N-Mesitylp yr r olid in e 27.37 1,4-Dibromo-
butane (21.6 g, 100 mmol) was added to a solution of 2,4,6-
trimethylaniline (13.52, 100 mmol) in 10 mL of ethanol. The
solution was maintained at 60 °C for 72 h. After addition of
J O001166L
(37) Akula, M. R.; Kabalka, G. W. Synth. Commun. 1998, 28, 2063-
2070.