Asymmetric and nonasymmetric addition of RLi and RMgX to 3- methoxynaphthalen-2-yl oxazolines and imines. An approach to substituted 2- tetralones

Article abstract of DOI:10.1021/jo991727c

Chiral and achiral 3-methoxynaphthalen-2-yl oxazolines 4a,b failed to undergo an aromatic nucleophilic displacement of the 3-methoxy group with organolithium reagents and instead afforded dihydronaphthalenes 9 and 14 in 30-95% yield. Dihydronaphthalenes 9 (racemic) and 14 (nonracemic) were easily converted into the corresponding aldehydes 15. Alternatively, aldehydes 15 were prepared via tandem addition of Grignard reagents to imines 17 in 50-65% yield. Aldehydes 15 served as precursors to 3,3,4-trisubstituted 2-tetralones 16. Use of methyl chloroformate to trap the azaenolate derived from 17f and i-PrMgCl afforded, in 65% yield, a versatile synthetic intermediate 23 which may serve to access 4-alkyl-, 3,4-dialkyl-, 3,4-disubstituted and 3,3,4- trisubstituted 2-tetralones with diverse substitution patterns.

Full text of DOI:10.1021/jo991727c

3018
J . Org. Chem. 2000, 65, 3018-3026
Asym m etr ic a n d Non a sym m etr ic Ad d ition of RLi a n d RMgX to
3-Meth oxyn a p h th a len -2-yl Oxa zolin es a n d Im in es. An Ap p r oa ch to
Su bstitu ted 2-Tetr a lon es†
Sergei V. Kolotuchin and A. I. Meyers*
Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523
Received November 4, 1999
Chiral and achiral 3-methoxynaphthalen-2-yl oxazolines 4a ,b failed to undergo an aromatic
nucleophilic displacement of the 3-methoxy group with organolithium reagents and instead afforded
dihydronaphthalenes 9 and 14 in 30-95% yield. Dihydronaphthalenes 9 (racemic) and 14
(nonracemic) were easily converted into the corresponding aldehydes 15. Alternatively, aldehydes
15 were prepared via tandem addition of Grignard reagents to imines 17 in 50-65% yield. Aldehydes
15 served as precursors to 3,3,4-trisubstituted 2-tetralones 16. Use of methyl chloroformate to trap
the azaenolate derived from 17f and i-PrMgCl afforded, in 65% yield, a versatile synthetic
intermediate 23 which may serve to access 4-alkyl-, 3,4-dialkyl-, 3,4-disubstituted and 3,3,4-
trisubstituted 2-tetralones with diverse substitution patterns.
Conjugate addition of organolithium and Grignard
lenes 6 which might further be elaborated, after hydroly-
sis, into chiral substituted 2-tetralones with diverse
substitution patterns, in high enantiomeric purity.
reagents to a naphthalene nucleus, activated by electron-
withdrawing groups, has been shown to be an attractive
approach to dihydronaphthalenes.1 However, use of
naphthalenes having a methoxy substituent in the
activated ring for the addition has been only sparsely
studied. One example of such a study involved addition
of a series of organolithium reagents to chiral naphthyl-
oxazoline1h 1 to afford methyl vinyl ethers 2 which were
converted into nonracemic highly substituted 1-tetralones
3 in good chemical and optical yields (Scheme 1). A study
was, therefore, initiated to examine the feasibility of a
similar approach to the corresponding 2-tetralones in
direct analogy to the process documented for 1. 2-Tetral-
ones are known precursors to 2-aminotetralins which
display a variety of biological activities.2 This report is
concerned with addition of certain organometallics to
3-methoxynaphthalen-2-yl oxazolines 4 and imines 5 in
an effort to access chiral, nonracemic dihydronaphtha-
In earlier studies3,4 we found that addition of organo-
lithium or Grignard reagents to oxazolines 7 and 8
resulted in substitution of the methoxy group rather than
addition to the naphthalene nucleus. A distinct feature
of 7 and 8 is that their methoxy groups are found in the
1- or 2-position of the naphthalene ring which allows
them to undergo nucleophilic addition followed by their
displacement. Of further interest in the additions to 4a
and 4b was the general question “will conjugate addition
still occur at the 1-position or would the methoxy group
at C-3 still be displaced?” Nucleophilic addition of alkyl
anions (R) to 7 and 8 produces the σ-complexes 7a and
8a , respectively, yet these intermediates still contain an
unperturbed benzene ring in a conjugated styrene π-sys-
tem. The addition of a nucleophile to 4 would produce
σ-complex 4c having a cross-conjugated o-quinone me-
thide moiety providing a transition state of higher energy
than the potential energy of the isomeric styrene systems
in 7a and 8a . Invoking the concept of “partial bond
fixation”,5 the addition of nucleophiles to 4 should,
therefore, take place at the 1-position leaving the meth-
oxy enol ether unaffected.
† The paper is dedicated to the memory of Lendon N. Pridgen.
(1) (a) For the use of a hindered ester as an activating group for
naphthalene additions, see: Shindo, M.; Koga, K.; Asano, Y.; Tomioka,
K. Tetrahedron 1999, 55, 4955-4968. For the use of a carboxylate as
an activating group for naphthalene additions, see: (b) Plunain, B.;
Mortier, J .; Vaultier, J .; J . Org. Chem. 1996, 61, 5206-5207. For the
use of oxazolidine/imine system as an activating group for naphthalene
additions, see: (c) Pridgen, L. N.; Mokhallatie, M. K.; Wu, M.-J . J .
Org. Chem. 1992, 57, 1237-1241. (d) Mokhallatie, M. K.; Muralidha-
ran, K. R.; Pridgen, L. N. Tetrahedron Lett. 1994, 35, 4267-4270. For
the use of imine as an activating group for naphthalene additions,
see: (e) Meyers, A. I.; Brown, J . D.; Laucher, D. Tetrahedron Lett. 1987,
28, 5279-5282. (f) Meyers, A. I.; Brown, J . D.; Laucher, D. Tetrahedron
Lett. 1987, 28, 5283-5286. (g) Tomioka, K.; Shindo, M.; Koga, K.; J .
Am. Chem. Soc. 1989, 111, 8266-8268. For the use of 1,3-oxazoline
as an activating group for naphthalene additions, see: (h) Meyers, A.
I.; Roth, G. P.; Hoyer, D.; Barner, B. A.; Laucher, D. J . Am. Chem.
Soc. 1988, 110, 4611-4624. (i) Rawson, D. J .; Meyers, A. I. J . Org.
Chem. 1991, 56, 2292-2294.
(2) (a) Mellin, C.; Bjo¨rk, L.; Karle´n, A.; J ohansson, A. M.; Sundell,
S.; Kenne, L.; Nelson, D. L.; Ande´n, N.-E.; Hacksell, U. J . Med. Chem.
1988, 31, 1130-1140. (b) J ohansson, A. M.; Mellin, C.; Hacksell, U. J .
Org. Chem. 1986, 51, 5252-5258. See, also: Malmberg, A.; Nordvall,
G.; J ohansson, A. M.; Mohell, N.; Hacksell, U. Mol. Pharmacol. 1994,
46, 299-312; Chem. Abstr. 1994, 121, 194983h. Horn, A. S.; Dijkstra,
D.; Feenstra, M. G. P.; Grol, C. J .; Rollema, H.; Westerink, B. H. C.
Eur. J . Med. Chem.-Chem. Ther. 1980, 15, 387-92; Chem. Abstr. 1981,
94, 103044n. Beaulieu, M.; Itoh, Y.; Tepper, P.; Horn, A. S.; Kebabian,
J . W. Eur. J . Pharmacol. 1984, 105, 15-21. Chem. Abstr. 1985, 102,
437x.
(3) For reviews on oxazolines chemistry, see: (a) Gant, T. G.; Meyers,
A. I. Tetrahedron 1994, 50, 2297-2360. (b) Meyers, A. I. J . Heterocycl.
Chem. 1998, 35, 991-1002.
(4) (a) Gant, T. G.; Meyers, A. I. J . Am. Chem. Soc. 1992, 114, 1010-
1015. (b) Meyers, A. I.; Lutomski, K. A. Synthesis 1983, 105-107. (c)
Meyers, A. I.; Flanagan, M. E. Organic Syntheses; Wiley: New York,
1998; Coll. Vol. IX, pp 258-262.
(5) Advanced Organic Chemistry, 3rd ed.; March, J ., Ed.; J ohn Wiley
& Sons: New York, 1985; pp 39-41.
10.1021/jo991727c CCC: $19.00 © 2000 American Chemical Society
Published on Web 04/26/2000

An Approach to Substituted 2-Tetralones
J . Org. Chem., Vol. 65, No. 10, 2000 3019
Sch em e 1
Sch em e 2
Sch em e 3
to the CdN link of the oxazoline moiety to form oxazo-
lidine 10b with concomitant ring-chain tautomerism of
the oxazolidine to its imine form 13. The imine may be
deprotonated by MeLi and alkylated with MeI to give
ethyl ketone 12b on acidic hydrolysis. In the case of
n-BuLi addition only the n-butyl ketone 12a was ob-
tained, after aqueous hydrolysis of 10a . The addition of
tert-butyllithium-MeI to 4a afforded only 2-tert-butyl-
oxazolidine 10f.
The reaction of phenyldimethylsilyllithium6 with naph-
thyloxazoline 4a followed by MeI quench afforded methyl
ketone 12c as a major product in 65% yield, while
dihydronaphthalene 9c was isolated in only 30% yield.
Ketone 12c may be a result of an aza-Brook rearrange-
ment of 10c and alkylation of the intermediate benzylic
carbanion with methyl iodide (Scheme 3). A related aza-
Brook of (R-silylallyl)amines was reported by Mori and
Honda.7
When n-BuLi was added to 4a in THF at -78 °C, the
reaction resulted in the 1,4-addition product (9a ) and the
1,2-addition product (10a ) in 75% and 3% yield, respec-
tively (Scheme 2). Formation of oxazoline 11 arising from
a directed ortho-metalation of 4a ortho to the oxazolinyl
moiety was also observed in 5% yield.3a On treatment of
the reaction mixture with dilute acid, oxazolidine 10a
was hydrolyzed to the methyl ketone 12a which was
isolated and characterized. Thus, the hypothesis of the
high energy transition state leading to 4c appears valid,
and no methoxy group displacement products were
observed.
s-Butyllithium cleanly added to 4a to give 88% of the
desired dihydronaphthalene 9d as a 2:1 mixture of
diastereomers at the s-Bu stereogenic center. Phenyl-
lithium also cleanly afforded the corresponding dihy-
dronaphthalene 9e in 95% yield. Crystal structure8
determination of 9e (Figure 1) confirmed the relative
(6) (a) Fleming, I.; Newton, T. W.; Roessler, F. J . Chem. Soc., Perkin
Trans. 1 1981, 2527-2532. (b) Hulme, A. N.; Henry, S. S.; Meyers, A.
I. J . Org. Chem. 1995, 60, 1265-1270.
When methyllithium was added to 4a , the ethyl ketone
12b, unexpectedly, was the major product and the 1,4-
addition product 9b was obtained in only 28% yield after
methyl iodide quench (Scheme 3). Such poor yields of
MeLi-MeI addition to naphthyloxazolines have been
observed earlier.1h The yields of ethyl ketone 12b and
oxazoline 9b were not dependent on whether MeLi or a
complex of MeLi‚LiBr was used in the reaction. A pos-
sible pathway for the unexpected formation of ethyl
ketone 12b may involve an initial 1,2-addition of MeLi
(7) Honda, T.; Mori, M. J . Org. Chem. 1996, 61, 1196-1197.
(8) Crystal structure analysis of 9e: C23H25NO2, Mr 347.44, 0.18 ×
0.28 × 0.40 mm, monoclinic, P21/c, a ) 13.5764(6), b ) 8.0560(4), c )
19.1666(8) Å, R ) γ ) 90°, â ) 109.7530(10)°, V ) 1972.9(2) Å3, Z ) 4,
Fcalc ) 1.170 g/cm3, Mo KR (λ ) 0.71073 Å), T ) 171(2) K; µ ) 0.074
mm-1. Area detector data collected on
a Siemens SMART CCD
diffractomerer. A total of 12551 reflections were collected (1.59 < Θ <
28.33°); independent reflections 4748 (Rint ) 0.0657). Structure solved
by direct methods (SHELXTL) and refined by full-matrix least-squares
2
on |F| . Final R indices [I > 2σ(I)]: R1 ) 0.0556, wR2 ) 0.0962. GOF
) 0.912. Residual electron densitry (e‚Å-3) 0.246/-0.209.

3020 J . Org. Chem., Vol. 65, No. 10, 2000
Kolotuchin and Meyers
F igu r e 1. Crystal structure of 9e.
Sch em e 4
(R ) i-Pr, Et, respectively; synthesis vide infra) was
subjected to acidic hydrolyses. Surprisingly, enol ethers
15d ,f were found to be stable in 10% aqueous hydrochlo-
ric acid in THF (ca. 1:1, v/v) at room temperature. The
unusual stability of the enol ethers may be due to the
adjacent quaternary center. Deprotection of the methyl
vinyl ethers 15d ,f was subsequently achieved in a
mixture of THF, TFA, and a small amount of trifluo-
romethanesulfonic acid which afforded the 2-tetralones
16a ,b in 78% and 82% yield, respectively (Scheme 5). It
was observed that aldehydes 15 are shelf-stable com-
pounds for several days at room temperature before
decomposition products are detected by TLC, whereas the
corresponding neat 2-tetralones such as 16a decompose
to unidentified products over the same period of time and
should be stored in a freezer. Aldehyde 15d was con-
verted to the alcohol 16c with sodium borohydride which
was qualitatively more shelf-stable than starting alde-
hyde 15d . The enol ether 16c was transformed to the
tetralone 16d under the same conditions as above.
Furthermore, when 15d was treated with DDQ in re-
fluxing dioxane, it underwent simultaneous de-
formylation and aromatization to isopropylnaphthalene
16e.
stereochemistry of the process as being an overall trans-
addition. This finding is in agreement with the one
previously reported1h,i and implies that the 3-methoxy
group does not change the relative stereochemical out-
come of this tandem addition process.
The use of chiral nonracemic naphthyloxazoline 4b in
place of 4a was also investigated for the addition of
organolithium reagents in anticipation of reaching enan-
tiomerically pure adducts. Reaction of n-BuLi and PhLi
with oxazoline 4b afforded 14a and 14b as single
diastereomers in 56% and 60% yield, respectively (Scheme
4). The absolute stereochemistry of 14 is believed to be
as shown and is based on analogy to the previously
reported1h,i observation that the incoming organolithium
reagent approaches the face which is opposite to the
sterically demanding 4-tert-butyl group of the oxazolinyl
moiety.
To further explore the synthetic utility of dihydronaph-
thalene adducts such as 15 and capitalize on the fact that
no displacement of the 3-methoxy group in naphthalenes
4 was observed, an alternative route to aldehydes 15 was
investigated. This was based on the use of an imine as
the activating group for addition to the naphthalene
nucleus. It was earlier reported from these laboratories
that chiral nonracemic and achiral naphthylimines treated
with organolithium reagents furnished dihydronaphtha-
lenes 19b after aqueous hydrolysis in 60-90% yield.1e,f
An extension of this methodology was later communi-
cated by Pridgen who was able to effect highly diastereo-
selective addition of Grignard reagents to a chiral tau-
tomeric mixture of oxazolidine/imine 19a derived from
(R)-phenylglycinol and 1-naphthylcarboxaldehyde. Chiral,
nonracemic addition adducts (19b) were obtained in good
We have previously reported that products from the
addition of organolithiums to naphthyloxazolines such as
9 and 14 can be readily converted into carboxaldehydes.1h,4c
Both oxazolines 9a and 14b were smoothly transformed
into the corresponding aldehydes 15a ,b in 80% and 68%
yield, respectively.
To demonstrate the accessibility of highly substituted
chiral 2-tetralones from 15, enol ethers 15d and 15f

An Approach to Substituted 2-Tetralones
J . Org. Chem., Vol. 65, No. 10, 2000 3021
Sch em e 5
Sch em e 6
chemical yields and >90% ee.1c,d
exception of MeMgCl which gave aldehyde 15e in a poor
20% yield when the addition was conducted at 0 °C.1d
A
competing process in the addition of Grignard reagents
to naphthalenes 17 involved addition to the CdN linkage
furnishing 20. Naphthylamine 20a was isolated in 20%
yield and fully characterized.10,11
The addition of i-PrMgCl, EtMgBr, PhMgBr to (R)-
phenylglycinol imine 17c afforded enantiomerically en-
riched aldehydes 15b,d ,f in 33-56% yield and in 82-
95% ee as determined by HPLC (Scheme 6). Addition of
i-PrMgCl to (S)-alaninol imine 17d gave the opposite
enantiomer of 15d in 78% ee and 45% chemical yield.
The 1-phenylaldehyde 15b obtained by the addition of
PhMgBr to imine 17c had identical spectral character-
istics and specific rotation to aldehyde 15b obtained from
enantiomerically pure oxazoline 4b which suggests that
the absolute stereochemistry of 15b is as shown and the
entry of the nucleophile occurs from the side opposite the
phenyl moiety in the chelated imine intermediate, as
reported earlier by Pridgen and co-workers1c,d for a
related system.
In an effort to increase the yield of the desired
aldehydes 15 addition of i-PrMgCl to a series of imines
17 having various alkyl substituent in the amino alcohol
fragment was investigated. The results of this study
suggested an interesting trend in the influence of a
2-alkyl substituent of the 1,2-amino alcohol on the yield
of the recovered tandem addition product 15. Namely,
increasing the bulk of the 2-alkyl substituent results in
lower yields of aldehyde 15. This observation was con-
firmed by the addition of i-PrMgCl to imines 17b and
17e having a gem-dimethyl group and t-Bu substituent,
respectively. The reaction of 17b with i-PrMgCl gave a
low yield of tandem addition product 15d (12-15%). In
The requisite imines 17a -e were readily obtained by
heating naphthaldehyde 18 either with an excess or
equimolar amount of the corresponding 2-amino alcohol
with azeotropic removal of water. The reaction was
followed by the disappearance of the aldehyde proton
(δ(CDCl3) ) 10.3 ppm) in 18. gem-Dimethyl imine 17b
existed as its oxazolidine tautomer in solution while the
unsubstituted derivative 17a existed primarily as its
imine form. Furthermore, it is known that aldimines exist
almost exclusively in the E-configuration9 whereas the
remaining derivatives, 17c-e, were found to consist of
an equilibrating mixture of imine and both diastereo-
meric oxazolidines in solution (1H NMR).1c
A variety of Grignard reagents added readily to achiral
imine 17a in THF, and the intermediate aza-enolates
were trapped with MeI. The relative stereochemistry of
2-methylaldehydes 15 is shown in Scheme 6. This ster-
eochemistry is based on the analogy to the results
reported from this laboratory1e,f and by Pridgen and co-
workers.1c,d In all previous cases of the tandem addition
to chiral and achiral activated naphthalenes, the entry
of the electrophile on the planar lithio or magnesio
enolate or azaenolate occurs from the side opposite to the
group entering as the nucleophile.1 The yields of alde-
hydes 15 obtained ranged from 50% to 65% with the
(10) Use of excess of MeI resulted in partial methylation of the imine
addition adducts such as 20c and 20d , making their purification
difficult because of very close Rf values. Addition of Grignard reagents
to chiral nonracemic 17 may also suffer from poor diastereoselectivity,
resulting in the formation of two diastereomers at the newly created
stereogenic center which subsequently may get partially methylated.
Therefore, except for 20a -d , purification of the imine addition adducts
was not attempted, however, 1H NMR of the mixtures of the crude
adducts supported their identity.
(11) For the asymmetric addition of Grignard reagents to imines,
see: (a) Enders, D.; Reinhold: U. Tetrahedron: Asymmetry 1997, 8,
1895-1946. (b) Suzuki, Y.; Takahshi, H. Chem. Pharm. Bull. 1983,
31, 31-40. (c) Takahshi, H.; Suzuki, Y.; Inagaki, H. Chem. Pharm.
Bull. 1982, 30, 3160-3166.
(9) (a) Bjørgo, J .; Boyd, D. R.; Watson, C. G.; J ennings, W. B.; J erina,
D. M.; J . Chem. Soc., Perkin Trans. 2 1974, 1080-1084. (b) Karabatsos,
G. J .; Lande, S. S. Tetrahedron 1968, 24, 3907-3922.

3022 J . Org. Chem., Vol. 65, No. 10, 2000
Kolotuchin and Meyers
Sch em e 7
the case of tert-leucinol imine 17e exclusive addition to
the imine was observed. Amine 20b was formed in
quantitative yield upon aqueous NH4Cl quench of the
latter reaction mixture. For characterization purposes,
amine 20b was converted into a cyclic oxazolidone using
carbonyldiimidazole. Addition of allylmagnesium chloride
to 17a also gave exclusively a mixture of imine addition
adducts 20c and 20d . Benzylmagnesium chloride was
unreactive toward 17a and 95% of 18 was recovered after
the acidic hydrolysis.
followed by methyl chloroformate quench and hydrolysis,
an inseparable 1:2 mixture of 23 and 24 was obtained in
50% combined yield. The isopropyl ketone 24 undoubt-
edly arose from addition of i-PrMgCl to the ester group
of the intermediate imine which was converted to 23 after
aqueous hydrolysis. The formyl group in 23 was readily
removed with potassium cyanide in refluxing methanol
to afford ester 25. The relative stereochemistry of 25 was
supported by a small J H-H coupling of H-3 and H-4 of
1.3 Hz which implies a trans relationship between
4-isopropyl and 3-carboxymethyl groups. Examination of
ester 25 revealed it to be a product of a tandem addition
of i-PrMgCl or i-PrLi to 3-methoxy-2-carbomethoxynaph-
thalene (22) followed by a proton quench. Such a syn-
thetic transformation is normally not possible because
organolithium or Grignard reagents chemoselectively
react with the ester moiety and not the naphthalene
nucleus.1a However, this transformation would be highly
desirable since 1,2-disubstituted-1,2-dihydronaphtha-
lenes are found in a number of natural products.1h
As above, the methoxyvinyl ether in 25 was trans-
formed, under acidic conditions, to 2-tetralone 26 which
To assess the importance of the appended hydroxyl
group in imines 17 and its influence on the addition of
Grignard reagents, imines 17f,g, having the hydroxyl
group spaced from the imine nitrogen by three and four
methylene groups, respectively, were prepared. Addition
of i-PrMgCl to 17f,g followed by MeI quench gave 27%
and 44% yield of the addition product 15d , respectively.
This suggested that the appended hydroxyl group might
not be necessary for the tandem addition to naphthalene
to occur. This notion was supported by the fact that imine
17h having no appended hydroxyl gave 39% of dihydro-
naphthalene 15d and 23% of unreacted naphthylalde-
hyde 18 when 2 equiv of i-PrMgBr in THF at 0 °C were
employed. However, the same finding implies that the
appended hydroxy group increased the rate of the addi-
tion. It was further found that using a 3-fold excess of
i-PrMgBr and raising the temperature from 0 °C to room
temperature afforded dihydronaphthalene 15d in 65%
yield. Use of EtMgBr in place of i-PrMgBr under the
latter conditions afforded 42% yield of 15f, and 58% of
18 was also recovered. We reported earlier that imine
21 readily added organolithium reagents to afford the
corresponding dihydronaphthalenes after aqueous hy-
drolysis.1e,f In the present study it was found that use of
3 equiv of a Grignard reagent at room temperature
drastically accelerated the rates of addition and tandem
additions to imine 17h .
1
existed in its enol form as evidenced by H NMR. The
carbomethoxy group of 26 was cleanly removed under
Krapcho conditions12 to provide 4-isopropyl- 2-tetralone
(27) in 85% yield.13,14
To access a 3,4-dialkyl disubstituted 2-tetralone 30, the
ester 25 was first deprotonated with LiHMDS and the
corresponding enolate was alkylated with MeI. The
vinylmethyl ether of 28 was first hydrolyzed and the ester
was decarbomethoxylated with LiCl in refluxing DMF.
The desired 4-isopropyl-3-methyl-2-tetralone (30) (Scheme
7) was obtained in 81% yield and was found to exist as a
3:1 mixture of trans- and cis-isomers, respectively. It
should be noted that reduction of the carboxaldehyde
moiety of 23 to a methyl group would produce the
3-epimer of dihydronaphthlene 28.
In conclusion, we have demonstrated that (3-methoxy-
2-naphthyl)oxazolines 4 do not undergo aromatic nucleo-
philic substitution of the 3-methoxy group with organo-
lithium reagents and afford, instead, dihydronaphthalenes
9 and 14. Dihydronaphthalenes 9 and 14 were readily
converted into the corresponding aldehydes, 15. The
latter were also prepared via a tandem addition of
(12) Krapcho, A. P. Synthesis 1982, 805-822 and 893-914.
(13) For an example of an alternative synthesis of 4-alkyl-2-
tetralones, see: (a) Vebrel, J .; Carrie´, R. Bull. Soc. Chim. Fr. 1982, II,
116-124. (b) Vebrel, J .; Carrie´, R. Bull. Soc. Chim. Fr. 1982, II, 161-
166.
(14) For general approaches to 2-tetralones, see: (a) Burckhalter,
J . H.; Campbell, J . R.; J . Org. Chem. 1961, 26, 4232-4235. (b)
Rosowsky, A.; Battaglia, J .; Chen, K. K. N.; Modest, E. J .; J . Org. Chem.
1968, 33, 4288-4290. (c) Sims, J . J .; Cadogan, M.; Selman, L. H.
Tetrahedron Lett. 1971, 951-954. (d) Simms, J . J .; Selman, L. H.;
Cadogan, M. Organic Syntheses; Wiley: New York, 1988; Coll. Vol.
VI, pp 744-746. (e) Shner, V. F.; Przhiyaglovskaya, N. M. Russ. Chem.
Rev. (Engl. Transl.) 1966, 35, 523-531. (f) Rosowsky, A.; Chen, K. K.
N.; Papathanasopoulos, N.; Modest, E. J . J . Heterocycl. Chem. 1972,
9, 263-273. (g) Soffer, M. D.; Bellis, M. P.; Gellerson, H. E.; Stewart,
R. A. Organic Syntheses; Wiley: New York, 1963; Coll. Vol. IV, pp 903-
906.
In all examples shown thus far, methyl iodide was
utilized as an electrophilic quenching reagent to form
2-methyl aldehydes 15. However, we also employed
methyl chloroformate as an electrophile to trap the aza-
enolate obtained from 17f and i-PrMgCl. This gave, after
hydrolysis, a 65% yield of aldehyde 23 (Scheme 7).
Interestingly, when 17a was treated with i-PrMgCl

An Approach to Substituted 2-Tetralones
J . Org. Chem., Vol. 65, No. 10, 2000 3023
the solvent was concentrated. The residue was dissolved in
25 mL of THF and 5 mL of water, and 720 mg oxalic acid
dihydrate was added. The solution was stirred at room
temperature for 4 h, the solvent rotoevaporated, and the
residue was partitioned between dichloromethane and water.
The collected organic layer was dried (Na2SO4), decanted, and
mixed with 20 mL of silica gel. After concentration, the product
was placed on silica gel packed in 10%AcOEt/hexanes and
eluted with the same solvent increasing percentage of AcOEt
to 50%AcOEt/hexanes to neat AcOEt to 5%MeOH/AcOEt to
afford 980 mg (75%) of 9a as a colorless oil: 1H NMR δ 7.30-
7.03 (4H, m), 5.57 (1H, s), 3.95 (2H, AB-q), 3.74 (3H, s), 2.70
(1H, m), 1.80-1.10 (6H, series of m), 1.41 (3H, s), 1.35 (3H, s),
1.33 (3H, s), 0.85 (3H, t, J ) 7.0); 13C NMR δ 167.4, 160.7,
133.6, 133.0, 128.0, 126.3, 124.8, 124.1, 96.3, 78.6, 66.5, 55.5,
51.0, 46.5, 30.7, 30.0, 28.4, 28.2, 23.5, 22.9, 14.0. MS 327.
HRMS Calcd for C21H29NO2 327.2202; Found 327.2198. IR
1644.
Also recovered: 30 mg (3%, highest Rf) of 2-pentanoyl-3-
methoxynaphthalene (12a ) as a yellowish oil: 1H NMR δ 8.09
(1H, s), 7.86 (1H, d, J ) 8.0), 7.76 (1H, d, J ) 8.0), 7.53 (1H,
m),7.40 (1H, m), 7.20 (1H, s), 4.02 (3H, s), 3.06 (2H, m), 1.73
(1H, m), 1.56 (1H, m), 0.98 (3H, t, J ) 7.3). 13C NMR δ 203.8,
155.1, 135.7, 130.4, 130.3, 128.8, 128.0, 127.8, 126.2, 124.2,
106.1, 55.5, 43.4, 26.6, 22.5, 14.0. MS 242. IR 1679. Positive
2,4-DNP test on TLC.
Grignard reagents to imines 17. It was further demon-
strated that aldehydes 15, possessing an enol ether resi-
due, serve as precursors to 3,3,4-trisubstituted 2-tetral-
ones 16. The appended hydroxy group in imines 17 may
not be essential for the addition of Grignard reagents to
the aromatic ring since cyclohexyl imine 21 also reacted
with Grignard reagents in this manner. However, lack
of the appended hydroxy group in 21 required higher
temperatures and a larger excess of the Grignard re-
agents. Use of methyl chloroformate to trap the aza-
enolate derived from 17f and i-PrMgCl afforded, in 65%
yield, a highly versatile synthetic intermediate 23 which
served as an example of a precursor to 4-alkyl-substituted
and 3,4-dialkyl-substituted 2-tetralones.
Exp er im en ta l Section 15
4,4-Dim eth yl-2-(2-(3-m eth oxyn a p h th yl))oxa zolin e (4a ).
Yield 85% from the corresponding acid. White crystals: mp
125-127 °C. 1H NMR δ 8.29 (1H, s), 7.83 (1H, d, J ) 8.0),
7.75 (1H, d, J ) 8.0), 7.51 (1H, m), 7.37 (1H, m), 7.21 (1H, s),
4.19 (2H, s), 4.00 (3H, s), 1.47 (6H, s). 13C NMR δ 161.1, 155.4,
135.3, 132.0, 128.1, 127.7, 127.5, 126.2, 124.0, 119.1, 106.3,
79.0, 67.5, 56.0, 28.3. IR 1631, 1468, 1195. MS 255. Anal. Calcd
for C16H17NO2: C, 75.27; H, 6.71; N, 5.49; O, 12.53. Found:
C, 75.44; H, 6.72; N, 5.60.
(-)-(S)-4-ter t-Bu t yl-2-(2-(3-m et h oxyn a p h t h yl))oxa zo-
lin e (4b). Yield 75% from the corresponding acid. A yellowish
oil: 1H NMR δ 8.26 (1H, s), 7.83 (1H, d, J ) 8.0), 7.75 (1H, d,
J ) 8.4), 7.50 (1H, m), 7.40 (1H, m), 7.21 (1H, s), 4.43 (1H,
m), 4.32 (1H, m), 4.16 (1H, m), 4.00 (3H, s), 1.06 (9H, s). 13C
NMR δ 162.1, 155.3, 135.3, 131.7, 128.1, 127.7, 127.5, 126.2,
124.0, 119.2, 106.2, 76.2, 68.5, 55.9, 34.0, 25.8. [R]D ) -50.8
(CH2Cl2, c 1.25). MS 283.
Typ ica l P r oced u r es for t h e Ad d it ion of R Li t o 4.
(()-1,2-Dihydro-1-s-butyl-2-methyl-2-(5-(3,3-dimethyloxazol-
in yl))-3-m eth oxyn aph th alen e (9d). To a magnetically stirred
clear solution of 255 mg (1 mmol) of 4a in 9 mL of dry THF
cooled to -78 °C was added dropwise 2.2 mL (2.64 mmol) of
s-BuLi (1.2 M/cyclohexane). After the addition of the organo-
lithium was complete, the resulting red clear solution was
stirred at -78 °C for 2 h and quenched with 0.5 mL (8 mmol)
of neat MeI added dropwise. The resulting orange solution was
stirred at -78 °C for 30 min and allowed to warm to room
temperature at which time an orange solid formed. The orange
suspension was stirred for 30 min while immersed into a room-
temperature water bath. The resulting yellowish suspension
was partitioned between water and dichloromethane. The
collected organic layer was dried (Na2SO4), and decanted, and
the solvent was rotoevaporated to dryness. The resulting
yellowish oil was chromatographed over silica gel eluting with
1% AcOEt/CH2Cl2 to yield 290 mg (88%) of the desired 9d as
a yellowish oil: 1H NMR δ (major) 7.30-7.03 (4H, m), 5.50
(1H, s), 3.93 (2H, m), 3.73 (3H, s), 2.81 (1H, d, J ) 1.6), 2.00-
1.00 (3H, series of multiplets), 1.40 (3H, s), 1.37 (3H, s), 1.34
(3H, s), 0.92 (3H, t, J ) 7.0), 0.67 (3H, d, J ) 6.7). MS 327. IR
1643.
(()-1,2-Dih yd r o-1-n -bu tyl-2-m eth yl-2-(2-(4,4-d im eth yl-
oxa zolin yl))-3-m eth oxyn a p h th a len e (9a ). To a magneti-
cally stirred clear solution of 1.02 g (4 mmol) of 4a in a mixture
of 40 mL of THF and 10 mL of diethyl ether cooled to -95 °C
(acetone/dry ice/L N2) was added dropwise 3.0 mL (7.5 mmol)
of n-BuLi (2.5 M/hexanes). After the addition of the organo-
lithium was complete, the resulting orange clear solution was
stirred at -78 °C for 6 h and quenched with 0.5 mL (8 mmol)
of neat MeI added dropwise and warmed to room-temperature
overnight. The solvent was rotoevaporated, and the residue
was partitioned between water and dichloromethane. The
collected organic layer was dried (Na2SO4) and decanted, and
50 mg (5%, lowest Rf) of 4,4-dimethyl-2-(2-(1-methyl-3-
methoxynaphthyl))oxazoline (11) as a yellowish oil: 1H NMR
δ 8.00 (1H, d, J ) 8.0), 7.75 (1H, d, J ) 7.7), 7.49 (1H, m),
7.41 (1H, m), 7.05 (1H, s), 4.19 (2H, s), 3.94 (3H, s), 2.69 (3H,
s), 1.49 (6H, s). MS 269.
(()-1,2-Dih yd r o-1,2-d im eth yl-2-(2-(4,4-d im eth yloxa zol-
in yl))-3-m eth oxyn aph th alen e (9b). Using a procedure analo-
gous to that for 9a , 2.5 mL of MeLi (3.5 mmol, 1.4 M/diethyl
ether) was added to 255 mg (1 mmol) of 4a in 5 mL of THF at
-78 °C. The resulting orange solution was stirred for 20 min
at -78 °C and overnight at -30 °C. The reaction was quenched
with 0.5 mmol (8 mmol) of MeI. The workup as for 9a and
column chromatography (5% AcOEt/hexanes to 10% AcOEt/
hexanes) afforded 80 mg (28%) of 9b as a yellowish oil: 1H
NMR δ 7.30-7.03 (4H, m), 5.65 (1H, s), 3.88 (2H, AB-q), 3.76
(3H, s), 3.00 (1H, q, J ) 7.0), 1.50 (3H, s), 1.31 (6H, s), 1.31
(3H, d, J ) 7.0); 13C NMR δ 167.0, 160.0, 135.7, 133.0, 126.3,
125.9, 125.0, 124.7, 96.8, 78.8, 66.5, 55.5, 45.5, 44.7, 28.4, 28.2,
23.0, 17.0. MS 285. IR 1644.
There were also recovered 100 mg (47%) of 2-propanoyl-3-
methoxynaphthalene (12b) as a yellowish oil: 1H NMR δ 8.13
(1H, s), 7.86 (1H, d, J ) 8.0), 7.76 (1H, d, J ) 8.0), 7.54 (1H,
m),7.30 (1H, m), 7.22 (1H, s), 4.02 (3H, s), 3.09 (2H, t, J )
7.3), 1.25 (3H, t, J ) 7.3). 13C NMR δ 203.8, 155.1, 135.6, 130.4,
130.3, 128.8, 128.0, 127.7, 126.2, 124.2, 106.0, 55.4, 36.9, 8.5.
MS 214. IR 1681. Positive 2,4-DNP test on TLC.
(()-1,2-Dih yd r o-1-(p h en yld im eth ylsilyl)-2-m eth yl-2-(2-
(4,4-d im eth yloxa zolin yl))-3-m eth oxyn a p h th a len e (9c). A
mixture of 550 mg (3.2 mmol) of dimethylphenylsilane and 230
mg (33 mmol) of Li metal was sonicated for 2 h at room
temperature. The resulting deep red solution was cannulated
to a solution of 255 mg (1 mmol) of 4a in 8 mL of THF cooled
to -78 °C, and the mixture was allowed to react overnight at
-78 °C and quenched with 0.8 mL (13 mmol) of MeI. The
products were chromatographed over silica gel (CH2Cl2 to
20%AcOEt/CH2Cl2) to afford 120 mg (30%) of the desired 9c
as a yellowish oil that crystallized on standing: mp 114-116
°C. 1H NMR δ 7.40-7.20 (5H, m), 7.20-6.80 (4H, m), 5.46 (1H,
s), 3.62 (3H, s), 3.59 (1H, d, J ) 7.8), 2.70 (2H, m), 1.35 (3H,
s), 1.09 (3H, s), 0.79 (3H, s), 0.32 (3H, s), -0.24 (3H, s); 13C
NMR δ 167.0, 161.9, 140.4, 133.1, 132.9, 132.3, 128.8, 127.9,
127.5, 125.2, 124.3, 123.9, 96.6, 77.9, 65.9, 55.5, 44.6, 41.5, 29.0,
27.1, 24.3, 1.8, -3.4. HRMS Calcd for C25H31SiNO2 405.2118;
Found 405.2124.
There was also recovered 130 mg (65%) of 2-acetyl-3-
methoxynaphthalene (12c) as a yellowish oil: 1H NMR δ 8.15
(1H, s), 7.82 (1H, d, J ) 8.0), 7.71 (1H, d, J ) 8.0), 7.54 (1H,
m), 7.30 (1H, m), 7.16 (1H, s), 3.98 (3H, s), 2.66 (3H, s). MS
200. IR 1679. Positive 2,4-DNP test on TLC.
(15) tert-Leucinol was prepared by NaBH4-I2 reduction of tert-
leucine; cf. McKennon, M. J .; Meyers, A. I. J . Org. Chem. 1993, 58,
3568-3571.

3024 J . Org. Chem., Vol. 65, No. 10, 2000
Kolotuchin and Meyers
(()-1,2-Dih yd r o-1-p h en yl-2-m eth yl-2-(2-(4,4-d im eth yl-
oxa zolin yl))-3-m eth oxyn a p h th a len e (9e). Using a proce-
dure analogous to that for 9d , 255 mg (1 mmol) of 4a was
treated with 1.5 mL (2.7 mmol) of PhLi (1.8 M cyclohexane/
diethyl ether) at -22 °C overnight, cooled to -78 °C, and
quenched with 0.5 mL (8 mmol) of MeI. Purified by column
chromatography over silica gel (2% AcOEt/CH2Cl2) to afford
330 mg (95%) of 9e as an off-white solid: mp 141-143 °C
(heptane). 1H NMR δ 7.30-6.87 (9H, m), 5.75 (1H, s), 4.10 (1H,
s), 3.77 (3H, s), 3.70 (1H, d, J ) 7.7), 3.25 (1H, d, J ) 7.7),
1.58 (3H, s), 1.20 (3H, s), 1.15 (3H, s); 13C NMR δ 166.5, 159.9,
141.0, 133.6, 133.4, 129.5, 128.3, 127.9, 126.8, 125.3, 125.0,
97.4, 78.8, 66.3, 57.4, 55.6, 46.9, 28.6, 27.7, 24.3. MS 347. IR
1644. Anal. Calcd for C23H25NO2: C, 79.51; H, 7.25; N, 4.03;
O, 9.21. Found: C, 79.47; H, 7.18; N, 4.03.
(()-4,4-Dim e t h yl-2-t er t -b u t yl-2-(2-(3-m e t h oxyn a p h -
th yl))oxa zolid in e (10f). Using a procedure analogous to that
for 9d , 255 mg (1 mmol) of 4a was treated with 1.5 mL (2.55
mmol) of t-BuLi (1.7 pentane). The product was purified by
column chromatography over silica gel (5% hexanes/CH2Cl2)
to afford 315 mg (96%) of 10f as an off-white solid: mp 119-
121 °C (hexane). 1H NMR δ 8.07 (1H, s), 7.86 (1H, d, J ) 8.0),
7.78 (1H, d, J ) 8.0), 7.49 (1H, m),7.43 (1H, m), 7.23 (1H, s),
4.00 (3H, s), 3.85 (1H, s br), 3.76 (1H, d J ) 7.6), 3.47 (1H, d
J ) 7.6), 1.32 (3H, s), 1.04 (3H, s), 1.03 (9H, s). 13C NMR δ
156.3, 133.6, 131.9, 129.0, 128.2, 128.0, 126.1, 125.8, 123.7,
106.1, 103.0, 57.2, 55.0, 39.7, 29.9, 27.2, 26.0. Anal. Calcd for
amino alcohol and traces of benzene. The residual oil was
dissolved in 50 mL of 40% CH2Cl2/hexanes, and the solvent
was allowed to evaporate slowly while the solution was sitting
in the hood at which time the imine crystallized. The material
was suspended in a mixture of 50 mL of hexanes and 5 mL of
CH2Cl2 and filtered to afford 3.1 g (82%) of the desired 17a as
a solid: mp 71-73 °C. 1H NMR δ (imine) 8.83 (1H, s), 8.42
(1H, s), 7.85 (1H, d, J ) 8.5), 7.72 (1H, d, J ) 8.0), 7.48 (1H,
m), 7.38 (1H, m), 7.08 (1H, s), 3.98 (2H, m), 3.89 (3H, s), 3.84
(2H, m). 13C NMR δ 159.3, 155.9, 135.5, 128.7, 128.1, 127.4,
127.2, 126.2, 125.1, 123.9, 105.2, 63.8, 62.3, 55.2. MS 229. IR
3359.
The yields for other imines 17 were close to quantitative.
3,3-Dimethyl-5-(2-(3-methoxynaphthyl))oxazolidine (17b).
An off-white solid: mp 99-101 °C. 1H NMR δ (oxazolidine)
8.04 (1H, s), 7.83 (1H, d, J ) 8.0), 7.77 (1H, d, J ) 8.0), 7.49
(1H, m), 7.41 (1H, m), 7.18 (1H, s), 5.96 (1H, s), 4.00 (3H, s),
3.82 (1H, d J ) 7.3), 3.70 (1H, d J ) 7.0), 2.40 (1H, br s), 1.40
(6H, s), 1.04 (3H, s), 1.03 (9H, s).
1H NMR δ (imine) 8.91 (1H, s), 8.45 (1H, s), 7.86 (1H, d, J
) 8.8), 7.75 (1H, d, J ) 8.8), 7.17 (1H, s), 3.63 (1H, s), 1.35
(3H, s). MS 257. IR 3387.
(+)-(R)-2-P h en yl-2-(1-(3-m et h oxyn a p h t h yl)m et h ylen -
a m in o))eth a n ol (17c). An off-white solid: mp 98-100 °C. 1H
NMR δ (imine) 8.96 (1H, s), 8.63 (1H, d, J ) 8.4), 7.94 (1H, d,
J ) 8.1), 7.75 (1H, d, J ) 8.1), 7.60-7.20 (7H, m), 7.09 (1H,
s), 4.65 (1H, m), 4.15 (1H, m), 4.03 (1H, m), 3.86 (3H, s), 3.00
(1H, br s). [R]D ) +162.2 (c 3.5, CH2Cl2) after 15 min
equilibration in solution. Anal. Calcd for C20H19NO2: C, 78.66;
H, 6.27; N, 4.59; O, 10.48. Found: C, 78.44; H, 6.13; N, 4.71.
(+)-(S)-2-Met h yl-2-(1-(3-m et h oxyn a p h t h yl)m et h ylen -
a m in o))eth a n ol (17d ). An off-white solid: mp 135-137 °C.
1H NMR δ (imine) 8.87 (s, 1H), 8.47 (s, 1H), 7.88 (1H, d, J )
7.7), 7.73 (1H, d, J ) 8.4), 7.40 (1H, m), 7.37 (1H, m), 7.10
(1H, s), 3.90 (3H, s), 3.80 (m), 3.75 (m), 1.32 (3H, d, J ) 6.2).
[R]D ) +33.8 (c 1.6, CH2Cl2) after 15 min equilibration in
solution.
C
20H27NO2: C, 76.64; H, 8.68; N, 4.47; O, 10.21. Found: C,
76.60; H, 8.66; N, 4.45.
(+)-(S,S,S)-1,2-Dih yd r o-1-n -bu tyl-2-m eth yl-2-(2-(4-ter t-
bu tyloxa zolin yl))-3-m eth oxyn a p h th a len e (14a ). Using a
procedure analogous to that for 9d , 255 mg (0.9 mmol) of 4b
in 9 mL of THF was treated with 1.0 mL (2.5 mmol) of n-BuLi
(2.5 M/ hexanes) at -78 °C for 10 min, -30 °C for 10 min, and
0 °C for 10 min. The resulting red solution was cooled to -78
°C and quenched with 0.8 mL (13 mmol) of MeI. Purified by
column chromatography over silica gel as for 9d (2% AcOEt/
CH2Cl2) to afford 180 mg (56%) of the desired 14a as colorless
oil. Further purification of 14a was achieved by thin-layer
preparative radial chromatography (3% AcOEt/hexanes): 1H
NMR δ 7.30-7.03 (4H, m), 5.57 (1H, s), 4.15 (2H, m), 3.84 (1H,
m), 3.72 (3H, s), 2.73 (1H, m), 1.65 (2H, m), 1.45 (3H, s), 1.31-
1.11 (4H, m), 0.94 (9H, s), 0.85 (3H, t, J ) 7.0); 13C NMR δ
169.0, 160.9, 133.9, 133.1, 128.0, 126.3, 124.8, 124.1, 96.3, 74.9,
68.3, 55.4, 51.0, 46.7, 33.8, 31.0, 30.2, 25.7, 23.6, 22.9, 14.0.
MS 355. HRMS Calcd for C23H33NO2 355.2516; Found 355.2511.
IR 1643.8. [R]D ) +35.0 (c 1.6, CH2Cl2).
(-)-(S,S,S)-1,2-Dih yd r o-1-p h en yl-2-m eth yl-2-(2-(4-ter t-
bu tyloxa zolin yl))-3-m eth oxyn a p h th a len e (14b). Using a
procedure analogous to that for 9d , 517 mg (1.81 mmol) of 4b
was treated with 2.5 mL (4.5 mmol) of PhLi (1.8 M cyclohex-
ane/diethyl ether) at -78 °C for 6 h and quenched with 0.5
mL (8 mmol) of MeI. Purified by column chromatography over
silica gel as for 9a (5% AcOEt/CH2Cl2 to 25% AcOEt/CH2Cl2)
to afford 400 mg (59%) of the desired 14b as colorless oil.
Further purification of 14b was achieved by thin-layer pre-
parative radial chromatography (5% AcOEt/hexanes to 25%
AcOEt/hexanes): 1H NMR δ 7.30-6.80 (4H, m), 5.73 (1H, s),
4.13 (1H, s), 3.86 (1H, m), 3.71 (3H, s), 3.64 (1H, m), 3.38 (1H,
m), 1.61 (3H, s), 0.85 (9H, s); 13C NMR δ 168.0, 19.9, 141.2,
133.8, 133.4, 129.2, 128.3, 127.9, 126.8, 126.7, 125.2, 125.0,
97.2, 74.5, 68.5, 57.1, 55.4, 47.4, 33.8, 25.5, 24.2. MS 375. [R]D
) -173.0 (c 2.0, CH2Cl2). Anal. Calcd for C23H25NO2: C, 79.96;
H, 7.78; N, 3.75; O, 8.52. Found: C, 79.68; H, 7.80; N, 3.76.
There were also recovered 140 mg (27%) of the starting 4b.
Typ ica l P r oced u r e for th e Syn th esis of Im in es 17. 2-(2-
(3-Met h oxyn a p h t h yl)m et h ylen a m in o))et h a n ol (17a ). A
mixture of 3.05 g (16.4 mmol) of 18 and 3.3 g (54 mmol) of
2-aminoethanol in 60 mL of benzene was heated to reflux
overnight with concomitant removal of water with the aid of
a Dean-Stark trap. 1H NMR indicated the reaction to be
complete (disappearance of the aldehyde proton (δ ) 10.6)).
The solvent was rotoevaporated, and the yellow residue
obtained was subjected to short-path Kugelrohr distillation at
ca. 1 mmHg heating the pot to <120 °C to remove excess of
(-)-(S)-2-ter t-Bu t yl-2-(1-(3-m et h oxyn a p h t h yl)m et h yl-
1
en a m in o))eth a n ol (17e). A yellowish oil. H NMR δ (imine
and two diastereomeric oxazolidines) 8.83 (s), 8.52 (s), 7.93 (s),
7.90 (d, J ) 8.1), 7.82 (d, J ) 8.0), 7.77 (d, J ) 8.0), 7.76 (d, J
) 8.0), 7.50 (m), 7.39 (m), 7.20 (s), 7.18 (s), 7.16 (s), 5.88 (s),
5.75 (s), 4.00 (s), 3.97 (s), 3.93 (m), 3.75 (t, J ) 8.0), 3.35 (t, J
) 7.7), 3.07 (t, J ) 6.2), 1.07 (s), 1.04 (s), 1.03 (s). [R]D ) -20.2
(c 2.5, CH2Cl2)
3-(2-(3-Me t h oxy n a p h t h yl)m e t h y le n a m in o ))-1-p r o -
p a n ol (17f). A yellowish oil: 1H NMR δ (imine) 8.81 (1H, t, J
) 1.4), 8.38 (1H, s), 7.86 (1H, d, J ) 7.3), 7.75 (1H, d, J ) 8.0),
7.48-7.34 (2H, m), 7.17 (1H, s), 4.00 (3H, s), 3.95 (2H, m), 3.89
(2H, m), 3.25 (2H, m). 1H NMR δ (cyclic) 8.00 (1H, s), 7.82
(1H, d, J ) 8.0), 7.75 (1H, d, J ) 8.0), 7.48-7.34 (2H, m), 7.17
(1H, s), 5.60 (1H, s), 4.38 (1H), 4.01 (3H, s), 3.45 (1H, m), 2.02
(4H, m).
3-(2-(3-Me t h o x y n a p h t h y l)m e t h y le n a m in o ))-1-b u -
1
ta n ol (17g). A yellowish oil. H NMR δ (imine) 8.86 (1H, t, J
) 1.3), 8.39 (1H, s), 7.89 (1H, d, J ) 8.0), 7.75 (1H, d, J ) 8.4),
7.48-7.34 (2H, m), 7.18 (1H, s), 4.02 (3H, s), 3.76 (4H, m), 1.86
(4H, m). 13C NMR δ 157.5, 156.1, 135.5, 128.9, 128.3, 127.8,
127.4, 126.37, 125.2, 124.1, 105.5, 62.8, 61.7, 55.7, 33.7, 28.9.
Cycloh exyl Im in e of 18 (17h ). A yellowish oil. 1H NMR δ
8.90 (1H, s), 8.48 (1H, s), 7.89 (1H, d, J ) 8.0), 7.75 (1H, d, J
) 8.0), 7.48-7.34 (2H, m), 7.16 (1H, s), 4.00 (3H, s), 3.35 (1H,
m), 2.00-1.60 (6H, m), 1.40 (4H, m). 13C NMR δ 156.1, 154.9,
135.3, 128.7, 128.4, 127.2, 127.0, 126.2, 126.0, 123.8, 105.3,
70.4, 55.4, 34.5, 25.7, 25.0.
Gen er a l P r oced u r e for th e Ad d ition of Gr ign a r d
Rea gen ts to 17. To a magnetically stirred solution of 2 mmol
of 17 in 8-9 mL of dry THF cooled to -78 °C was added
dropwise 3 mL (6 mmol) of a Grignard reagent (2 M/THF). In
cases where 1 M solutions of a Grignard in THF were used, 6
mL (6 mmol) of a Grignard reagent (1 M/THF) were added to
17 with concomitant decrease of THF to 5 mL. After the
addition of the Grignard reagent was complete, the resulting
amber solution was stirred at -78 °C for 5 min and transferred
to -30 °C bath and stirred for 2 h and 10-14 h (overnight) at

An Approach to Substituted 2-Tetralones
J . Org. Chem., Vol. 65, No. 10, 2000 3025
0 °C at which time the solution became darker. The solution
was cooled to -30 °C, quenched with 1 mL (16 mmol) of neat
MeI, and allowed to warm to 0 °C. The resulting suspension
was stirred at 0 °C for 3 h, and 2 h at room temperature. The
resulting white suspension was quenched by the addition of 8
mL of water followed by 8 mL of 10% aq HCl, and the resulting
mixture was stirred for 10 h (overnight) at room temperature
and partitioned between water and dichloromethane. The
collected organic layer was dried (Na2SO4), decanted, and
mixed with 20 mL of silica gel. The solvent was removed and
the residue loaded on silica gel. Elution with 5% EtOAc/hexane
gradually increasing to 10% AcOEt and further to 20% AcOEt/
hexanes. Elution of the column with 10% MeOH/acetone or
10% MeOH/CH2Cl2 provided crude imine addition products as
oils which were further purified by preparative radial thin-
layer chromatography (Chromatotron) over silica gel eluting
with 2% MeOH/CH2Cl2. Analogously, the crude dihydronaph-
thalenes obtained as above were further purified by prepara-
tive radial thin-layer chromatography (Chromatotron) over
silica gel eluting with a gradient of Et2O in hexanes (hexanes
to 3% Et2O/hexanes to 10% Et2O/hexanes) to afford the desired
products 15 as yellowish oils.
Additions to imine 17h followed the same general procedure
as for 17a -g except that (a) the addition of the Grignard
reagent was done at room temperature, (b) the reaction was
carried out at room temperature for 18 h, (c) hydrolysis of the
tandem addition products after the alkylation step to remove
the cyclohexylimine was carried out with 10% aq HCl instead
of 1/1 (v/v) 10% aq HCl/water.
(()-1,2-Dih yd r o-1-n -b u t yl-2-m et h yl-3-m et h oxyn a p h -
th a len e-2-ca r boxa ld eh yd e (15a ). The desired 15a was
obtained in 80% from 9a by the earlier procedure as a colorless
oil: 1H NMR δ 10.19 (1H, s), 7.30-7.03 (4H, m), 5.66 (1H, s),
3.80 (3H, s), 2.73 (1H, dd, J ) 3.6, J ) 9.8), 1.80-1.61 (2H,
m), 1.40-1.00 (4H, m), 1.17 (3H, s), 0.77 (3H, t, J ) 7.3); 13C
procedure1h,2e NMR δ 205.6, 160.5, 133.1, 132.7, 128.5, 126.7,
125.2, 124.5, 96.2, 55.4, 53.3, 50.2, 29.9, 29.7, 22.7, 19.0, 13.9.
MS 258. IR 1724. Positive 2,4-DNP test on TLC.
(()-1,2-Dih yd r o-1-p h en yl-2-m eth yl-3-m eth oxyn a p h th -
a len e-2-ca r boxa ld eh yd e (15b). For the synthesis of racemic
15b from 17a , the reaction was carried out at room-temper-
ature overnight rather than at (-30 °C to 0 °C). Yield 57% as
a yellowish oil: 1H NMR δ 9.37 (1H, s), 7.30-6.90 (8H, m),
5.90 (1H, s), 4.11 (1H, s), 3.79 (3H, s), 1.33 (3H, m); 13C NMR
δ 203.0, 158.5, 138.6, 133.4, 133.0, 129.3, 128.6, 128.3, 127.3,
127.2, 125.7, 125.4, 98.3, 55.8, 55.6, 54.4, 18.4. MS 278. IR
1725. Anal. Calcd for C19H18O2: C, 81.99; H, 6.52; O 11.50.
Found: C, 81.82; H, 6.60. Positive 2,4-DNP test on TLC.
Nonracemic (+)-(S,S) 15b obtained in 40% yield from 17c:
92% ee by HPLC, [R]D ) +52.7 (c 1.3, CH2Cl2); nonracemic
(+)-(S,S)-15b obtained in 58% yield from 14b: [R]D ) +60.3
(c 2.0, CH2Cl2).
(()-1,2-Dih yd r o-1-vin yl-2-m et h yl-3-m et h oxyn a p h t h -
a len e-2-ca r boxa ld eh yd e (15c). 65% Yield as a yellowish
oil: 1H NMR δ 9.71 (1H, s), 7.30-7.03 (4H, m), 5.97 (1H, m),
5.80 (1H, s), 5.21 (2H, m), 3.78 (3H, s), 3.49 (1H, d, J ) 9.9),
1.25 (3H, m); 13C NMR δ 202.9, 158.5, 135.3, 133.0, 131.9,
127.3, 125.6, 125.2, 118.6, 97.0, 55.4, 54.5, 53.6, 16.5. Positive
2,4-DNP test on TLC.
(()-1,2-Dih yd r o-1-isop r op yl-2-m eth yl-3-m eth oxyn a p h -
th a len e-2-ca r boxa ld eh yd e (15d ). 63% Yield as a yellowish
oil: 1H NMR δ 10.24 (1H, s), 7.30-7.03 (4H, m), 5.62 (1H, s),
3.80 (3H, s), 2.73 (1H, d, J ) 3.3), 2.15 (1H, m), 1.19 (3H, s),
0.89 (3H, d, J ) 6.6), 0.83 (3H, d, J ) 6.6); 13C NMR δ 205.8,
161.1, 134.7, 130.1, 129.1, 127.0, 124.9, 124.2, 97.0, 56.1, 55.6,
52.6, 30.3, 22.7, 20.4, 18.2. MS 244. HRMS Calcd for C16H20O2
244.1463; Found 244.1463. IR 1720. Positive 2,4-DNP test on
TLC.
The reaction of 16a and i-PrMgCl also afforded 20% of N-(2-
hydroxyethyl)-N-methyl-1-(3-methoxynaphthyl)-2-methylpro-
pylamine (20a ) as a yellowish oil: 1H NMR δ 7.81 (1H, d, J )
8.8), 7.77 (1H, d, J ) 8.4), 7.63 (1H, s), 7.47 (1H, m), 7.38 (1H,
m), 7.20 (1H, s), 4.06 (1H, d, J ) 9.0), 3.96 (3H, s), 3.70 (1H,
m), 3.60 (1H, m), 2.80 (1H, br), 2.68 (1H, m), 2.46 (2H, m),
2.22 (3H, s), 1.22 (3H, d, J ) 6.2), 0.77 (3H, d, J ) 6.5). 13C
NMR δ 156.8, 133.3, 128.0, 127.8, 127.6, 127.5, 126.1, 125.0,
123.5, 105.0, 65.0, 57.9, 55.5, 55.3, 35.3, 29.0, 20.9, 20.5. HRMS
Calcd for (C18H25NO2‚H+) 288.1968; Found 288.1963. IR 3416
cm-1
.
Nonracemic (+)-(S,S)-15d obtained from 17c in 33% yield:
98% ee by HPLC, [R]D ) +190.5 (c 0.8, CH2Cl2); nonracemic
(-)-(R,R) obtained from 17d in 45% yield: 73% ee by HPLC,
[R]D ) -132.0 (c 1.6, CH2Cl2)
(()-1,2-Dih yd r o-1,2-d im eth yl-3-m eth oxyn a p h th a len e-
2-ca r boxa ld eh yd e (15e). Yield 20% as a yellowish oil: 1H
NMR δ 9.92 (1H, s), 7.30-7.03 (4H, m), 5.75 (1H, s), 3.80 (3H,
s), 3.0 (1H, q, J ) 7.0), 1.32 (3H, d, J ) 7.3), 1.24 (3H, s); 13C
NMR δ 204.4, 159.2, 135.4, 132.6, 126.8, 126.4, 125.6, 125.2,
97.1, 55.5, 53.6, 43.9, 17.7, 16.3. MS 216. Positive 2,4-DNP
test on TLC.
There were also recovered 64% of the starting 18.
(()-1,2-Dih yd r o-1-eth yl-2-m eth yl-3-m eth oxyn a p h th a -
len e-2-ca r boxa ld eh yd e (15f). Yield 52% as a yellowish oil:
1H NMR δ 10.19 (1H, s), 7.30-7.03 (4H, m), 5.66 (1H, s), 3.80
(3H, s), 2.65 (1H, dd, J ) 3.5, J ) 9.8), 1.73 (2H, m), 1.18 (3H,
s), 0.83 (3H, t, J ) 6.6); 13C NMR δ 205.8, 160.6, 132.8, 132.6,
128.9, 126.8, 125.2, 124.4, 96.3, 55.5, 53.3, 51.8, 22.9, 19.1, 12.3.
MS 230. IR 1725. Positive 2,4-DNP test on TLC.
Nonracemic (+)-(S,S)-15f obtained from 17c in 56% yield:
82% ee by HPLC, [R]D ) +155.0 (c 0.7, CH2Cl2).
(()-1,2-D ih y d r o -1-is o p r o p y l-2-m e t h y l-2-(h y d r o x y -
m eth yl)-3-m eth oxyn a p h th a len e (16c). The desired 16c was
obtained by reduction of 320 mg (1.33 mmol) of 15d with 82
mg (2.2 mmol) of NaBH4 in 25 mL of MeOH at room
temperature. The extractive workup gave 318 mg (100%) of
16c as a colorless oil: 1H NMR δ 7.20-6.90 (4H, m), 5.49 (1H,
s), 4.14 (1H, dd, J ) 3.7, J ) 15.0), 3.75 (3H, s), 3.70 (1H, d,
J ) 8.8, J ) 11.4), 2.49 (1H, d, J ) 3.3), 2.37 (1H, m), 2.18
(1H, m), 1.13 (3H, s), 0.90 (3H, d, J ) 7.0), 0.68 (3H, d, J )
7.0); 13C NMR δ 164.3, 135.2, 130.6, 130.1, 126.4, 124.3, 123.7,
96.6, 66.4, 55.2, 54.5, 42.1, 28.3, 23.0, 22.9, 17.4. MS 246. IR
3404.
1-Isop r op yl-2-m eth yl-3-m eth oxyn a p h th a len e (16e). A
mixture of 130 mg (0.5 mmol) of 15d , 130 mg (0.6 mmol) of
DDQ in 3 mL of dry dioxane was heated for 5 h. Chromato-
graphic purification over silica gel afforded 60 mg (53%) of the
desired 16e as an oil: 1H NMR δ 8.26 (1H, d, J ) 8.0), 7.79
(1H, d, J ) 8.0), 7.44 (2H, m), 7.08 (1H, s), 4.00 (3H, s), 2.50
(3H, s), 1.60 (6H, d, J ) 5.5). In 13C NMR there were observed
several unresolved resonances possibly due to hindered rota-
tion of the isopropyl group. MS 214. HRMS Calcd for C15H18
O
214.1357; Found 214.1358. Anal. Calcd for C15H18O: C, 84.07;
H, 8.47; O, 7.47. Found: C, 84.18; H, 8.49.
(()-1,2-Dih yd r o-1-isop r op yl-2-for m yl-2-ca r bom eth oxy-
3-m eth oxyn a p h th a len e (23). The general procedure for
aldehydes 15 was followed except that 6 equiv of methyl
chloroformate were added at -78 °C as an electrophilic
quenching agent. The resulting reddish solution was kept at
-78 °C for 2 h, at -25 °C for 2 and 1 h at room temperature.
A yellowish solid: mp 91-93 °C. 1H NMR δ 10.11 (1H, s),
7.20-7.01 (4H, m), 5.75 (1H, s), 3.86 (3H, s), 3.72 (1H, d, J )
3.7), 3.64 (3H, s), 2.22 (1H, m), 0.98 (3H, d, J ) 7.0), 0.85 (3H,
d, J ) 7.0); 13C NMR δ 198.6, 168.7, 153.8, 133.7, 129.5, 127.2,
125.2, 124.8, 99.8, 99.7, 65.3, 56.0, 52.9, 51.5, 29.2, 22.7, 18.6.
MS 288. IR 1746, 1719. Positive 2,4-DNP test on TLC.
(()-N-(2-Hydr oxyeth yl)-1-(3-m eth oxyn aph th yl)-3-bu ten -
a m in e (20c). The reaction of allylmagnesium chloride and
17a , following the general procedure with the exception that
it was run at room temperature, afforded 53% of 20c as a
yellowish oil: 1H NMR δ 7.79 (1H, d, J ) 8.8), 7.77 (1H, d, J
) 9.2), 7.73 (1H, s), 7.47 (1H, m), 7.38 (1H, m), 7.18 (1H, s),
5.76 (1H, m), 5.10 (1H, d, J ) 20.8), 5.05 (1H, d, J ) 14.3),
4.24 (1H, t, J ) 7.0), 4.00 (3H, s), 3.75 (1H, m), 3.63 (1H, m),
3.49 (2H, s br), 2.75 (m, 4H). 13C NMR δ 155.8, 135.0, 133.7,
130.5, 128.4, 127.7, 127.5, 126.2, 123.8, 117.4, 105.6, 60.3, 58.2,
55.4, 48.7, 39.8. IR 3321.3 cm-1
.
There was also recovered 18% of (()-N-(2-hydroxyethyl)-N-
methyl-1-(3-methoxynaphthyl)-3-butenamine (20d ) as a color-
less oil: 1H NMR δ 7.83 (1H, d, J ) 7.7), 7.78 (1H, d, J ) 8.0),
7.72 (1H, s), 7.49 (1H, m), 7.40 (1H, m), 7.21 (1H, s), 5.84 (1H,

3026 J . Org. Chem., Vol. 65, No. 10, 2000
Kolotuchin and Meyers
m), 5.10 (1H, m), 5.04 (1H, m), 4.46 (1H, t, J ) 7.0), 4.00 (3H,
s), 3.62 (2H, m), 3.35 (1H, br), 2.76 (m, 5H), 2.24 (3H, s). 13C
NMR δ 156.1, 135.9, 133.5, 128.8, 127.9, 127.7, 127.5, 126.0,
123.6, 117.3, 116.5, 105.5, 59.8, 58.1, 56.0, 55.2, 35.7, 33.3.
HRMS Calcd for (C18H24NO2‚H+) 286.1807; Found 286.1807.
(()-4-Eth yl-3-m eth yl-3-for m yl-2-tetr a lon e (16b). Yield
82% as a colorless oil: 1H NMR δ 10.26 (1H, s), 7.30-7.25 (4H,
m), 3.75 (2H, AB-q), 3.00 (1H, dd, J ) 3.6, J ) 11.4), 1.80 (1H,
m), 1.65 (1H, m), 1.11 (3H, s), 0.85 (3H, t, J ) 7.2); 13C NMR
δ 210.2, 203.0, 136.6, 131.0, 129.7, 128.3, 127.1, 126.5, 60.1,
IR 3416 cm-1
.
50.3, 42.4, 24.7, 20.1, 12.3. MS 216. IR 1723, 1709 cm-1
Positive 2,4-DNP test on TLC.
.
(-)-N-(1(S)-ter t-Bu t yl-2-h yd r oxyet h yl)-1-(3-m et h oxy-
n a p h th yl)-2-m eth ylp r op yla m in e (20b). Following the gen-
eral procedure, 375 mg (1.3 mmol) of 17e were treated with 2
mL (4 mmol) of i-PrMgCl (2 M/THF). The reaction was
quenched with a solution of 4 g of NH4Cl in 10 mL of water to
afford 325 mg (100%) of 20b as a colorless oil after extractive
workup with CH2Cl2: 1H NMR δ 7.81 (1H, d, J ) 8.4), 7.53
(1H, s br), 7.49 (1H, m), 7.41 (1H, m), 7.18 (1H, s), 3.98 (3H,
s), 3.70 (2H, m), 3.40 (1H, br), 2.30 (1H, br), 2.05 (1H, d, J )
4.4), 1.27 (3H, d, J ) 6.6), 0.88 (9H, s), 0.75 (3H, d, J ) 6.5).
13C NMR contained several broad unresolved signals and only
14 carbon resonances. [R]D ) -36.0 (c 0.7, CH2Cl2).
(-)-Ca r ba m a te of (-)-N-(1(S)-ter t-Bu tyl-2-h yd r oxyeth -
yl)-1-(3-m eth oxyn a p h th yl)-2-m eth ylp r op yla m in e (20b).
Obtained by treating the amine 20b with 360 mg (2.2 mmol)
of carbonyldiimidazole in 10 mL of dry CH2Cl2 at room-
temperature overnight. Purified by column chromatography
over silica gel (10% AcOEt/hexanes) to afford 320 mg (69%
from 17e) as a colorless oil: 1H NMR δ 8.11 (1H, s), 7.83 (1H,
d, J ) 7.7), 7.76 (1H, d, J ) 8.5), 7.45 (1H, m), 7.39 (1H, m),
7.13 (1H, s), 3.93 (3H, s), 2.92 (1H, d, J ) 5.3), 2.23 (1H, m),
1.86 (1H, d, J ) 3.7), 1.42 (1H, d, J ) 6.6), 1.20-1.16 (1H, m),
1.14 (3H, d, J ) 6.7), 0.83 (3H, d, J ) 6.5). 0.63 (9H, s). 13C
NMR δ 156.0, 133.7, 133.2, 129.0, 128.7, 127.6, 126.2, 125.6,
123.3, 104.2, 55.2, 46.6, 35.5, 32.5, 29.9, 27.0, 20.4, 19.4. IR
1623, 1592. [R]D ) -126.8 (c 2.1, CH2Cl2).
Typ ica l P r oced u r e for th e Dep r otection of th e Meth yl
Vin yl Eth er in Dih yd r on a p h th a len e Ad d u cts. (()-1,4-
Dih yd r o-4-isop r op yl-3-ca r b om et h oxy-2-h yd r oxyn a p h -
th a len e (26). To a clear solution of 400 mg (1.5 mmol) of 25
in 4 mL of THF were added 230 mg of water, 455 mg of TFA,
and 280 mg of trifluoromethanesulfonic acid. The resulting
yellowish solution was stirred for 2 h at room temperature.
The solvent was rotoevaporated, and the yellowish oil was
partitioned between dichloromethane and water. The collected
organic layer was dried (Na2SO4) and decanted, and the solvent
was rotoevaporated. The yellow oil obtained was purified by
preparative thin-layer radial chromatography over silica gel
(hexanes to 3% Et2O/hexanes to 10% Et2O/hexanes to 20%
Et2O/hexanes) to afford 360 mg (95%) of 26 as a yellowish oil:
1H NMR δ 12.47 (1H, s), 7.24 (4H, m), 3.88 (3H, s), 3.80 (2H,
m), 3.50 (1H, m), 2.01 (1H, m), 0.98 (3H, d, J ) 6.6), 0.73 (3H,
d, J ) 6.9); 13C NMR δ 172.3, 172.1, 137.0, 133.1, 128.8, 127.5,
126.0, 125.6, 100.0, 51.4, 45.2, 35.9, 35.3, 20.8, 18.6. MS 260.
IR 1656 cm-1. Positive 2,4-DNP test on TLC.
No attempts at obtaining elemental analysis on 26 and other
2-tetralones discribed in this account were made due to
decomposition over 1-2 days at room temperature. As for some
known unsubstituted 2-tetralones14d,g all 2-tetralones described
herein should be kept in a freezer for prolonged storage.
(()-4-Isop r op yl-3-m et h yl-3-for m yl-2-t et r a lon e (16a ).
Yield 78% as a colorless oil: 1H NMR δ 10.40 (1H, s), 7.30-
7.25 (4H, m), 3.77 (2H, AB-q), 3.10 (1H, d, J ) 4.0), 2.12 (1H,
m), 1.13 (3H, s), 0.93 (3H, d, J ) 7.0), 0.69 (3H, d, J ) 6.6);
13C NMR δ 211.5, 203.6, 133.7, 132.5, 131.0, 128.5, 127.1,
126.2, 59.0, 56.6, 42.1, 31.0, 23.1, 21.0, 18.2. MS 230. HRMS
Calcd for C15H18O2 230.1306; Found 230.1303. IR 1722, 1705
cm-1. Positive 2,4-DNP test on TLC.
(()-4-Isop r op yl-3-m eth yl-3-(h yd r oxym eth yl)-2-tetr a l-
1
on e (16d ). Yield 78% from 15d as a colorless oil. H NMR δ
7.30-7.13 (4H, m), 4.23 (1H, d, J ) 11.3), 3.66 (2H, AB-q),
2.86 (1H, d, J ) 3.3), 2.76 (1H, br s), 2.23 (1H, m), 1.14 (3H,
s), 0.95 (3H, d, J ) 7.0), 0.55 (3H, d, J ) 7.0); 13C NMR δ 217.0,
134.3, 133.3, 131.1, 127.8, 126.6, 125.7, 66.0, 56.0, 50.9, 42.1,
29.1, 23.0, 21.8, 16.8. MS 232. HRMS Calcd for C15H20O2
232.1463; Found 232.1463. IR 3454, 1699 cm-1. Positive 2,4-
DNP test on TLC.
(()-1,2-Dih yd r o-1-isop r op yl-2-ca r b om et h oxy-3-m et h -
oxyn a p h th a len e (25). To a clear solution of 440 mg (1.53
mmol) of 23 in 8 mL of anhydrous methanol was added all at
once 120 mg (1.85 mmol) of solid KCN. The clear yellow
solution was refluxed for 2 h, and the solvent was rotoevapo-
rated. The residue was partitioned between water and dichlo-
romethane, the collected organic layer was dried (Na2SO4), and
the solvent was rotoevaporated. The oily residue was purified
by preparative thin-layer radial chromatography over silica
gel (hexanes to 3% Et2O/hexanes to 10% Et2O/hexanes to 20%
Et2O/hexanes) to afford 390 mg (99%) of 25 as yellowish oil:
1H NMR δ 7.20-7.01 (4H, m), 5.67 (1H, s), 3.80 (3H, s), 3.64
(3H, s), 3.34 (1H, d, J ) 1.1), 2.97 (1H, dd, J ) 1.1, J ) 7.2),
1.96 (1H, m), 0.98 (3H, d, J ) 6.6), 0.89 (3H, d, J ) 6.9); 13C
NMR δ 172.5, 154.9, 133.6, 132.7, 128.9, 126.7, 125.2, 124.4,
98.1, 55.3, 52.2, 49.0, 46.7, 32.2, 20.9, 20.0. MS 260. IR 1732.
Anal. Calcd for C16H20O3: C, 73.82; H, 7.74. Found: C, 74.02;
H, 7.77.
(()-4-Isop r op yl-2-tetr a lon e (27). A clear solution of 340
mg (1.38 mmol) of 26 and 560 mg (13.1 mmol) of LiCl in 3 g of
DMF was refluxed for 3 h. The solution was cooled to room
temperature and partitioned between 10% Et2O/hexanes and
water. The collected organic layer was dried (Na2SO4) and
decanted, and the solvent was rotoevaporated. The yellow oil
obtained was purified by preparative thin-layer radial chro-
matography over silica gel (hexanes to 3% Et2O/hexanes to
10% Et2O/hexanes) to afford 210 mg (81%) of the desired 27
as yellowish oil: 1H NMR δ 7.30-7.15 (4H, m), 3.62 (2H, AB-
q), 2.85 (2H, m), 2.65 (1H, m), 1.83 (1H, m), 0.99 (3H, d, J )
6.6), 0.91 (3H, d, J ) 6.9); 13C NMR δ 210.6, 139.1, 132.9, 128.9,
128.5, 126.5, 126.0, 46.7, 43.6, 42.1, 31.7, 21.4, 19.8. MS 188.
IR 1701 cm-1
.
Ack n ow led gm en t. We thank the National Science
Foundation for generous support of this research pro-
gram. The authors also thank Dr. Susan M. Miller at
Colorado State University for solving the crystal struc-
ture of 9e.
Su p p or tin g In for m a tion Ava ila ble: Tables of X-ray data
and ORTEP for 9e; carbon-13 and proton spectra for 15
compounds: 4b, 9d ,e, 14a , 16a ,c,d , 17a ,f, 20c, 26. This
material is available free of charge via the Internet at
http://pubs.acs.org.
J O991727C