Benzotriazole-Mediated Stereoselective Olefination of Carboxylic Esters: Transformation of α-Amino Acid Esters into Chiral Allylamines

Article abstract of DOI:10.1021/jo971546f

Diastereoselective trans-olefinations of carboxylic esters 3a-h have been accomplished using benzylic or allylic benzotriazole derivatives 1a-e to prepare α-(benzotriazol-1-yl) ketones 4a-i, for the subsequent reduction of 4a-i, and finally for low-valent titanium-effected dehydroxybenzotriazolylation.¹ N-Protected α-amino acid esters 9a-c and 15 thus give allylamines 13a-e and 19 with virtually full retention of chirality. Mechanistic aspects of the dehydroxybenzotriazolylation are discussed.

Full text of DOI:10.1021/jo971546f

3438
J . Org. Chem. 1998, 63, 3438-3444
Ben zotr ia zole-Med ia ted Ster eoselective Olefin a tion of Ca r boxylic
Ester s: Tr a n sfor m a tion of r-Am in o Acid Ester s in to Ch ir a l
Allyla m in es
Alan R. Katritzky,* Dai Cheng, and J ianqing Li
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida,
Gainesville, Florida 32611-7200
Received August 19, 1997
Diastereoselective trans-olefinations of carboxylic esters 3a -h have been accomplished using
benzylic or allylic benzotriazole derivatives 1a -e to prepare R-(benzotriazol-1-yl) ketones 4a -i,
for the subsequent reduction of 4a -i, and finally for low-valent titanium-effected dehydroxyben-
zotriazolylation.1 N-Protected R-amino acid esters 9a -c and 15 thus give allylamines 13a -e and
19 with virtually full retention of chirality. Mechanistic aspects of the dehydroxybenzotriazolylation
are discussed.
Sch em e 1
In tr od u ction
Constructive olefination of carbonyl compounds is an
important transformation in organic synthesis. Wittig,
Peterson, and J ulia reactions are the three most fre-
quently used procedures.2 During the past two decades,
low-valent titanium-induced coupling of carbonyl com-
pounds has received wide application in intramolecular
cyclizations,3 while the unsymmetrical intermolecular
variant generally suffers from statistical crossovers.
Recently, Horikawa et al. reported that unsymmetric in-
termolecular coupling between carbonyl compounds and
dithioacetals with low-valent titanium generally gave
mixed cis- and trans-isomers with little stereoselectivity.4
Our recently published procedure of low-valent titanium-
effected dehydroxybenzotriazolylation1 has the advan-
tages of high stereoselectivity for trans-isomers and a
simple procedure. It constitutes an alternative to the
J ulia reaction, especially for benzylic and allylic sub-
strates.
Most olefination methods construct double bonds from
aldehydes and ketones. However, carboxylic esters have
been used in Horner-Wittig reactions to obtain selec-
tively (via selective reduction) threo-diastereomers of the
â-hydroxyphosphine oxides, which upon elimination led
stereospecifically to trans-alkenes.5 J ulia reactions have
been applied to construct double bonds from carboxylic
esters in some natural product syntheses.2c,6 Despite
this, little effort appears to have been made to study
systematically the olefination of carboxylic esters, al-
though carboxylic esters are frequently more easily
available than the corresponding aldehydes. For ex-
ample, the naturally occurring chiral R-amino acids are
easily converted to esters. In today’s era of asymmetric
synthesis, it is of great interest to explore these readily
available and enantiomerically pure compounds as build-
ing blocks and/or to introduce chiral centers.7,8
Successful olefinations of such compounds would lead
to allylamines (Scheme 1) which are of great synthetic9
and biological importance.10 Recent syntheses of chiral
allylamines include the following: (i) asymmetric allylic
amination;11 (ii) modification of enantiomerically pure
R-amino aldehydes;12 (iii) asymmetric addition to alkynes;13
and (iv) asymmetric nucleophilic addition to carbon-
nitrogen double bonds.14 However, most previous syn-
thetic transformations of the carboxyl groups of R-amino
acids have involved conversion into N-protected R-amino
aldehydes.15 Subsequent olefinations via Wittig-type
reactions suffer from a lack of general control of diaste-
reoselectivity in the formation of the double bond and
(7) Ager, D. J .; Prakash, I.; Schaad, D. R. Chem. Rev. 1996, 96,
835.
(8) Sardina, F. J .; Rapoport, H. Chem. Rev. 1996, 96, 1825.
(9) (a) Bargar, T. M.; McCowan, J . R.; McCarthy, J . R.; Wagner, E.
R. J . Org. Chem. 1987, 52, 678. (b) Murahashi, S.-I.; Taniguchi, Y.;
Imada, Y.; Tanigawa, Y. J . Org. Chem. 1989, 54, 3292. (c) Burgess,
K.; Ohlmeyer, M. J . J . Org. Chem. 1991, 56, 1027. (d) Zhang, Z.;
Scheffold, R. Helv. Chim. Acta 1993, 76, 2602.
(10) (a) Stu¨tz, A. Angew. Chem., Int. Ed. Engl. 1987, 26, 320. (b)
Perry, N. B.; Blunt, J . W.; Munro, M. H. G. Aust. J . Chem. 1991, 44,
627.
(11) (a) Hayashi, T.; Yamamoto, A.; Ito, Y.; Nishioka, E.; Miura, H.;
Yanagi, K. J . Am. Chem. Soc. 1989, 111, 6301. (b) Whitesell, J . K.;
Yaser, H. K. J . Am. Chem. Soc. 1991, 113, 3526.
(12) (a) Luly, J . R.; Dellaria, J . F.; Plattner, J . J .; Soderquist, J . L.;
Yi, N. J . Org. Chem. 1987, 52, 1487. (b) McKillop, A.; Taylor, R. J . K.;
Watson, R. J .; Lewis, N. Synthesis 1994, 31.
(1) Katritzky, A. R.; Li, J . J . Org. Chem. 1997, 62, 238.
(2) (a) Maguire, A. R. In Comprehensive Organic Functional Group
Transformations; Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.;
Pergamon Press: New York, 1995; Vol. 1, p 589. (b) Gosney, I.; Lloyd,
D. ibid., p 719. (c) Kelly, S. E. In Comprehensive Organic Synthesis;
Trost, B. M., Ed.; Pergamon Press: New York, 1991; Vol. 1, p 729.
(3) (a) McMurry, J . E. Chem. Rev. 1989, 89, 1513. (b) Fu¨rstner, A.;
Bogdanovic, B. Angew. Chem., Int. Ed. Engl. 1996, 35, 2443.
(4) Horikawa, Y.; Watanabe, M.; Fujiwara, T.; Takeda, T. J . Am.
Chem. Soc. 1997, 119, 1127.
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Soc. 1986, 108, 284.
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Soc. 1991, 113, 2321.
(14) (a) Enders, D.; Schankat, J . Helv. Chim. Acta 1993, 76, 402.
(b) Inoue, I.; Shindo, M.; Koga, K.; Tomioka, K. Tetrahedron: Asym-
metry 1993, 7, 1603. (c) Denmark, S. E.; Nakajima, N.; Nicaise, O.
J .-C. J . Am. Chem. Soc. 1994, 116, 8797. (d) Enders, D.; Schankat, J .
Helv. Chim. Acta 1995, 78, 970. (e) Merino, P.; Anoro, S.; Castillo, E.;
Merchan, F.; Tejero, T. Tetrahedron: Asymmetry 1996, 4, 1887.
(15) J urczak, J .; Golebiowski, A. Chem. Rev. 1989, 89, 149.
S0022-3263(97)01546-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 04/28/1998

Stereoselective Olefination of Carboxylic Esters
J . Org. Chem., Vol. 63, No. 10, 1998 3439
Ta ble 1. P r ep a r a tion of r-Bt Keton es 4a -i a n d Olefin s 5a -h
a
b
Overall yield starting from 4; selectivity ratios determined by 1H NMR. 2 equiv of LDA for entry 5; 1 equiv of BuLi for other entries.
c Two diastereomers without separation. Not isolated. e Overall yield based on 1e.
d
Sch em e 2a
racemization at the chiral centers.12a,15 N-Protected
R-amino aldehydes are relatively unstable, both chemi-
cally and configurationally,15 and their preparation from
the corresponding acids via esters or active amides is
lengthy.15,16
We now report a method for the stereoselective prepa-
ration of trans-alkenes 5a -h from carboxylic esters 3a -h
and benzylic or allylic benzotriazole derivatives 1a -e
(Scheme 2 and Table 1). This comprises the preparation
of R-(benzotriazol-1-yl) ketones 4a -i from benzylic or
allylic benzotriazole derivatives 1a -e and carboxylic
esters 3a -h , subsequent reduction of 4a -i to hydroxy
analogues 6a -i, and finally low-valent titanium-pro-
moted dehydroxybenzotriazolylation to give 5a -h . After
N-protection, R-amino acid esters 7a -c and 14 were
similarly converted into allylamines 13a -e and 19 with
a
For designation of individual compounds, see Table 1.
virtually full retention of the configuration of the chiral
centers (Schemes 4 and 5 and Table 2).
(16) Lubell, W. D.; Rapoport, H. J . Am. Chem. Soc. 1987, 109,
236.

3440 J . Org. Chem., Vol. 63, No. 10, 1998
Ta ble 2. P r ep a r a tion of Allyla m in es 13a -e
Katritzky et al.
Sch em e 3
ing to entry 4 of Table 1 required an elevated tempera-
ture because of steric hindrance in ester 3d , and the
higher temperature caused proton-exchange of product
4d with 2b, which caused almost half of the starting
material to be recovered. However, this problem was
solved by using 2 equiv of LDA as shown in entry 5 of
Table 1. 1-Allylbenzotriazole (1e) reacted with ester 3h
similarly to give product 4i, which was unstable and used
immediately for further reaction after aqueous workup.
The reduction of ketones 4a -i to hydroxy compounds
6a -i as mixtures of diastereomers was achieved in
virtually quantitative yields by using NaBH4 in ethanol
or a mixture of water and THF at 40 °C for 1 h.
According to 1H NMR, no ketones 4a -i were detected in
the crude intermediates 6a -i. The ratios of the two
possible diastereomers of 6a -i varied among different
substrates, but no high preferences and no obvious
pattern was found. The diastereomers of 6a -i were not
separated, and each pair of diastereomers was used
directly for the olefination step (Scheme 2).
a
Overall yield based on 1.
Resu lts a n d Discu ssion
P r ep a r a t ion of t h e St a r t in g Ma t er ia ls 1a -g.
1-Benzyl- and 1-allylbenzotriazoles 1 were readily pre-
pared either by refluxing of arylmethyl halides with ben-
zotriazole in toluene (for compounds 1a ,b, Table 1)17 or
by reacting the corresponding halides with benzotriazole
in the presence of sodium hydroxide (for compounds 1c,
1e, and 1g, Tables 1 and 2).1,18 1-[4-(N,N-Dimethylami-
no)benzyl]benzotriazole (1d ) (Table 1) was obtained from
the reaction of 1-(hydroxymethyl)benzotriazole with N,N-
dimethylaniline under acidic conditions.19 2-[(Benzotri-
azol-1-ylmethyl)-4-tert-butylfuran (1f) (Table 2) was pre-
pared by a previously reported20 ring construction method.
Olefin ation of Car boxylic Ester s 3a-h with 1-Ben -
zyl- a n d 1-Allylben zotr ia zoles 1a -e. Due to the
anion-stabilizing ability of the benzotriazolyl group,21
1-benzylbenzotriazoles 1a -e readily underwent lithiation
to generate the lithio derivatives 2a -e, which reacted
with carboxylic esters 3a -h to give R-(benzotriazol-1-yl)
ketones 4a -i in moderate to excellent yields (Scheme 2
and Table 1), in agreement with previously reported
methodology.22 The reactions of 2a and 2c,d with
aromatic esters 3a and 3f took place rapidly to give 4a
and 4f,g, in excellent yields. Slightly lower yields were
obtained for compounds 4b,c,e, and h . For compound
4e, this was probably due to already formed 4e being
lithiated by some of the 2c and also by double addition
of 2c to 3e. The lower yields for compounds 4b,c,h were
probably due to lithiation at the R-position of esters
3b,c,g, by the lithiated benzotriazole derivatives in place
of the desired addition reactions. In all cases, the yield
could probably be increased by exchanging the lithium
reagent with cerium chloride.23 The reaction correspond-
In our preliminary study,1 we found that the low-valent
titanium reagent, generated from the reduction of TiCl3
with lithium in THF or DME, effectively promoted
dehydroxybenzotriazolylation from N-(â-hydroxyalkyl)-
benzotriazoles to form an olefinic bond with the trans-
isomer predominating. In the present work, treatment
of the corresponding intermediates 6a -d with TiCl3/Li
in DME under reflux gave the expected alkenes 5a -d
(Scheme 2, Table 1). However, the yields of 5b,c by this
procedure were low, although the trans-selectivities were
excellent. We assumed that the low yields were probably
due to the poor reproducibility involved in the prepara-
tion of the TiCl3/Li system as McMurry and co-workers
reported.3a Therefore, the reagent TiCl3/Zu-Cu, reported
by McMurry and co-workers to be more reproducible,24
was employed, and this gave products 5a -h in moderate
to good yields. As shown in Table 1, the yields of 5b-d
were all considerably improved; however, it has to be
noted that selectivities were slightly lower with TiCl3/
Zn-Cu than with TiCl3/Li.
(17) (a) Katritzky, A. R.; Wu, J . Synthesis 1994, 597. (b) Katritzky,
A. R.; Zhang, G.; Xie, L. J . Org. Chem. 1997, 62, 721.
(18) (a) Gibson, M. S. J . Chem. Soc. 1956, 1076. (b) Katritzky, A.
R.; Xie, L.; Toader, D.; Serdyuk, L. J . Am. Chem. Soc. 1995, 117, 12015.
(19) Katritzky, A. R.; Lan, X.; Lam, J . N. Synthesis 1990, 341.
(20) Katritzky, A. R.; Li, J . J . Org. Chem. 1995, 60, 638.
(21) Katritzky, A. R.; Yang, Z.; Cundy, D. J . Aldrichim. Acta 1994,
27, 31.
We tentatively assume that the dehydroxybenzotri-
azolylation follows a mechanism similar to that of the
McMurry coupling3a as shown in Scheme 3. The diaster-
eomeric intermediates 6 on treatment with low-valent
titanium undergo sequential reductive cleavages to form
(22) Katritzky, A. R.; Wang, J .; Karodia, N.; Li, J . J . Org. Chem.
1997, 62, 4142.
(23) Lequeux, T. P.; Percy, J . M. J . Chem. Soc., Chem. Commun.
1995, 2111.
(24) McMurry, J . E.; Fleming, M. P.; Kees, K. L.; Krepski, L. R. J .
Org. Chem. 1978, 43, 3255.

Stereoselective Olefination of Carboxylic Esters
J . Org. Chem., Vol. 63, No. 10, 1998 3441
Sch em e 4
Sch em e 5
in CH2Cl2, to give 9a -c in almost quantitative yields.26
The N-protected R-amino esters 9a -c reacted with
lithium derivatives 2 to give ketones 11a -e, which were
reduced in situ with NaBH4 to form intermediates 10a -
e. After aqueous workup, the mixed diastereomeric pairs
of compounds 10a -e were each treated with low-valent
titanium followed by deprotection to afford allylamines
13a -e with trans-isomers predominating, in 40-54%
overall yields based on benzotriazole derivatives 1.
For L-proline 14, protection for the amino group was
effected with triethylsilyl chloride. This N-protected
L-proline 15 underwent the desired reaction with lithi-
ated 1-benzylbenzotriazole (2a ) and subsequent reduction
first metal-attached species A and then radical B. The
radical intermediate B rotates to the thermodynamically
favored configuration, from which elimination of the
benzotriazolyl group forms trans-alkenes 5. This pro-
posed mechanism explains the trans-alkene predomi-
nance and is supported by our experimental results and
by literature evidence.3a,24 On the basis of this mecha-
nism, the diastereoselectivity of the double-bond forma-
tion should depend on the rate at which the Bt group is
cleaved: the more slowly, the more time the radical
intermediate has available to rotate to the thermody-
namically favored configuration and the higher the
selectivity for the trans-isomers. Since Zn2+ cations,
generated from the reaction of TiCl3 with Zn-Cu couple,
assist the benzotriazolyl group to leave,25 higher yields
and lower selectivities are expected as compared with
TiCl3/Li in the cases of 5b,c. The selectivities also depend
on the bulkiness of the substituents R1 and R2 as can be
seen in Table 1.
1
of ketone 18 to give, according to the H NMR spectrum
of the crude mixture, a mixture of 16 and 17. Surpris-
ingly, treatment of the mixture of 16 and 17 with low-
valent titanium under the same reaction conditions as
above resulted in 25% conversion to the product 19 (based
on 1H NMR of the reaction mixture), after refluxing in
DME for 6 h; prolonging the heating time did not increase
the conversion. However, in the presence of NEt3, dehy-
droxybenzotriazolylation proceeded smoothly to give the
product 19 in 51% isolated yield. We believe that the
low conversion in the absence of NEt3 is probably due to
the formation of the metal complex as shown in Chart 1.
Ch a r t 1
Syn th esis of Allyla m in es 13a -e a n d 19 fr om
r-Am in o Acid Ester s 7a -c a n d 14. The above olefi-
nation method was successfully applied to commercially
available R-amino acid methyl ester hydrochlorides 7a -c
as shown in Schemes 4 and 5 and Table 2. Thus, the
amino groups of 7a -c were readily protected with bis-
(chlorodimethylsilyl)ethane (8) in the presence of NEt3
This type of complex is relatively stable under low-valent
titanium conditions as reported previously.27 NEt3 per-
(26) Djuric, S.; Venit, J .; Magnus, P. Tetrahedron Lett. 1981, 22,
1787.
(25) Katritzky, A. R.; Lan, X.; Fan, W.-Q. Synthesis 1994, 445.
(27) Newkome, G. R.; Roper, J . M. J . Org. Chem. 1979, 44, 502.

3442 J . Org. Chem., Vol. 63, No. 10, 1998
Katritzky et al.
with a Perkin-Elmer 341 polarimeter with the use of the
sodium D line.
haps decomposed this complex so that dehydroxybenzo-
triazolylation proceeded in the normal way. The conver-
sion of the N-protected intermediates 10a -e under
normal low-valent titanium conditions without NEt3 is
probably due to the bulky protecting group that makes
a five-membered-ring complex unfavorable.
P r ep a r a t ion of 2-[(Ben zot r ia zol-1-yl)m et h yl]-4-ter t-
bu tyl)fu r a n (1f). A solution of n-BuLi (37.5 mL of 1.6 M in
hexane, 60 mmol) was added dropwise with stirring to a
solution of 1-propargylbenzotriazole20 (9.6 g, 60 mmol) in THF
(100 mL) at -78 °C. The mixture was stirred at this temper-
ature for 1 h, and bromomethyl tert-butyl ketone (10.74 g, 60
mmol) was added slowly. The mixture was stirred for 4 h,
and t-BuOK (6.7 g, 60 mmol) in t-BuOH (30 mL) was added.
The reaction was warmed to room temperature and heated at
50 °C overnight. Water (100 mL) and EtOAc (100 mL) were
added, and the organic phase was washed with ammonium
chloride solution (3 × 100 mL) and dried with MgSO4. After
removal of the solvents, the residue was subjected to silica gel
column chromatography using ether/hexane (1:3) as eluent to
Deter m in a tion of En a n tiom er ic Excess. Two ex-
periments were conducted to determine the preservation
of chirality of this procedure. The trans-isomer of allyl-
amine 13d (homogeneous according to 1H and 13C NMR)
was converted into the corresponding amide with the en-
antiomerically pure (S)-(-)-R-methoxy-R-(trifluorometh-
yl)phenylacetic acid. Only a single diastereomer was
1
observed in the H NMR spectrum of the crude product
and in the 13C NMR spectrum of the purified product.
give 1f (11.48 g, 75%) as a white powder: mp 63-65 °C; H
1
NMR δ 1.54 (s, 9 H), 5.77 (s, 2 H), 6.39 (s, 1 H), 7.12 (s, 1 H),
7.37 (t, J ) 7.7 Hz, 1 H), 7.48 (t, J ) 7.7 Hz, 1 H), 7.59 (d, J
) 8.3 Hz, 1 H), 8.06 (d, J ) 8.3 Hz, 1 H); 13C NMR δ 29.8,
30.6, 45.2, 109.2, 109.8, 119.8, 123.8, 127.4, 132.8, 137.2, 137.3,
146.1, 147.8. Anal. Calcd for C15H17N3O: C, 70.56; H, 6.71;
N, 16.46. Found: C, 70.62; H, 7.07; N, 16.58.
Gen er a l P r oced u r e for P r ep a r a tion of r-(Ben zotr i-
a zol-1-yl) Keton es 4a -h . To a THF (40 mL) solution of 1 (8
mmol) in a lithiation bottle at -78 °C and protected with
nitrogen or argon was added the base (Table 1) dropwise. The
resulting dark blue solution was stirred at -78 °C for 15 min.
The corresponding ester 3 (8.4 mmol) was added dropwise as
a solution in dry THF (5 mL) and the temperature raised if
necessary (Table 1). After the dark color disappeared, satu-
rated NH4Cl solution (20 mL) was added. After the mixture
reached room temperature, it was diluted with CH2Cl2 (80 mL)
and water (50 mL). The organic phase was separated, washed
with water (80 mL), and dried with MgSO4. Evaporation of
the solvent under reduced pressure followed by separation (see
each compound) gave the product 4.
Second, the trans-isomer of 13a , containing less than 2%
1
of the cis-isomer according to the H NMR ratio, had an
optical rotation of [R]22 ) +25.8 (c 1.16, CHCl3), which
D
is in agreement with the literature value of +25.9 (c 0.9,
CHCl3) for 97% (R).14a Therefore, we conclude that the
transformations of R-amino acid esters 7a ,b and 14 to
chiral allylamines 13a -d and 19 proceeded with full
retention of the configuration at the chiral centers.
Con clu sion
In conclusion, we have described a method that links
carboxylic esters with benzyl or allyl groups to form
carbon-carbon double bonds with generally good selec-
tivity for trans-isomers. It has also been demonstrated
that this procedure can be used on N-protected R-amino
acid esters to synthesize allylamines with retention of
the chirality. The present constructive method consti-
tutes a novel route featuring cheap starting materials
and reagents, a simple experimental procedure, satisfac-
tory overall yields, a general preference for trans-olefi-
nation, and virtually full retention of the chirality.
r-P h en yl-r-(ben zotr ia zol-1-yl)m eth yl 4-Meth ylp h en yl
Keton e (4a ). Crystallization of the reaction mixture from
ether: mp 161-163 °C; 1H NMR δ 2.40 (s, 3 H), 7.20-7.40
(m, 10 H), 7.86 (s, 1 H), 7.91 (d, J ) 8.1 Hz, 2 H), 8.00-8.05
(m, 1 H); 13C NMR δ 21.7, 68.1, 111.6, 120.0, 123.8, 127.4,
129.1, 129.26, 129.34, 129.7, 132.1, 133.2, 133.3, 145.4, 146.7,
192.2. Anal. Calcd for C21H17N3O: C, 77.04; H, 5.23; N, 12.84.
Found: C, 76.91; H, 5.25; N, 12.95.
Exp er im en ta l Section
THF and DME were distilled prior to use from a purple
solution resulting from benzophenone and sodium. CH2Cl2 for
N-protection was distilled after refluxing for 24 h in the
presence of P2O5 and was stored over molecular sieves. The
Zn-Cu couple was prepared and stored according to the
literature method.24 The HCl/ethanol solution was prepared
by passing HCl gas through absolute alcohol and the concen-
tration calculated according to the weight difference. Column
chromatography was carried out on MCB silica gel (230-400
mesh). Other chemicals were used as obtained from com-
mercial sources. The (S)-(-)-R-methoxy-R-(trifluoromethyl)-
phenylacetic acid was >98.5% enantiomerically pure according
to the commercial source.
r-P h en yl-r-(ben zotr ia zol-1-yl)m eth yl n -Hep tyl Keton e
(4b). Silica gel column chromatography with hexane/ethyl
acetate (1:1) as eluent followed by evaporation of the solvents
1
gave the solid product: mp 88-89 °C; H NMR δ 0.84 (t, J )
6.5 Hz, 3 H), 1.12-1.32 (m, 8 H), 1.60-1.66 (m, 2 H), 2.61 (t,
J ) 7.3 Hz, 2 H), 6.78 (s, 1 H), 7.20-7.40 (m, 8 H), 8.04 (d, J
) 7.8 Hz, 1 H); 13C NMR δ 14.0, 22.5, 23.6, 28.8, 31.5, 40.8,
71.3, 110.7, 120.0, 123.9, 127.5, 129.0, 129.2, 129.4, 132.5,
133.0, 146.3, 203.1. Anal. Calcd for C21H25N3O: C, 75.19; H,
7.52; N, 12.53. Found: C, 75.01; H, 7.92; N, 12.60.
r-1-Na p h th yl-r-(ben zotr ia zol-1-yl)m eth yl Isobu tyl Ke-
ton e (4c). Crystallization of the reaction mixture from
hexane/ethyl acetate (1:1): mp 124-125 °C; 1H NMR δ 0.97-
1.01 (m, 6 H), 2.27-2.37 (m, 1 H), 2.62 (d, J ) 6.9 Hz, 2 H),
7.10-7.15 (m, 1 H), 7.20-7.27 (m, 2 H), 7.50-7.63 (m, 5 H),
7.80-8.11 (m, 4 H); 13C NMR δ 22.4, 22.6, 24.9, 68.7, 111.1,
120.0, 122.7, 123.7, 124.8, 126.6, 127.2, 127.4, 127.5, 127.7,
129.2, 130.9, 132.1, 133.3, 134.3, 146.5, 203.4. Anal. Calcd for
Reactions were routinely carried out under dry nitrogen or
argon atmosphere with magnetic stirring.
Melting points were determined on a hot-stage apparatus
without correction. NMR spectra were obtained with a Varian
Gemini-300 spectrometer at 75 MHz for 13C and 300 MHz for
1
1H. Both 13C and H NMR spectra were obtained in chloroform-
C22H21N3O: C, 76.93; H, 6.17; N, 12.24. Found: C, 76.81; H,
d, and chemical shift values are reported as δ downfield from
TMS as an internal standard. The 13C chemical shifts are
given to one decimal place unless this would involve two
resolved peaks being reported with identical chemical shifts.
The NMR spectra reported are the peaks assigned to the trans-
isomers. Some spectra also contain small peaks for the cis-
isomers unresolved by column chromatography. High-reso-
lution mass spectra and elemental analyses were performed
within the department. Optical rotation values reported for
13b-d and 19 were of the mixtures of cis- and trans-isomers
and for 13a of the purified trans-isomer and were measured
6.20; N, 12.21.
r-1-Naph th yl-r-(ben zotr iazol-1-yl)m eth yl ter t-Bu tyl Ke-
ton e (4d ). Crystallization of the reaction mixture from
hexane/ethyl acetate (1:1): mp 188-189 °C; H NMR δ 1.31
(s, 9 H), 7.16-7.28 (m, 3 H), 7.48-7.52 (m, 2 H), 7.59 (t, J )
7.5 Hz, 1 H), 7.66 (d, J ) 6.9 Hz, 1 H), 7.87-7.92 (m, 1 H),
7.93-8.01 (m, 2 H), 8.12-8.18 (m, 2 H); 13C NMR δ 26.7, 44.9,
63.7, 111.9, 119.8, 122.5, 123.6, 124.6, 126.6, 127.0, 127.2,
127.5, 127.8, 129.2, 131.1, 131.7, 133.5, 134.4, 146.7, 209.7.
Anal. Calcd for C22H21N3O: C, 76.93; H, 6.17; N, 12.24.
Found: C, 76.67; H, 6.32; N, 12.15.
1

Stereoselective Olefination of Carboxylic Esters
J . Org. Chem., Vol. 63, No. 10, 1998 3443
r-(4-Meth ylp h en yl)-r-(ben zotr ia zol-1-yl)m eth yl 4-(Di-
m eth yla m in o)p h en yl Keton e (4e). Silica gel column chro-
matography with ethyl acetate as eluent followed by evapo-
ration of the solvents gave the solid product: mp 217-219 °C;
1H NMR δ 2.33 (s, 3 H), 3.06 (s, 6 H), 6.63 (d, J ) 9.0 Hz, 2
H), 7.16, (d, J ) 7.5 Hz, 2 H), 7.28-7.31 (m, 5 H), 7.83 (s, 1
H), 7.92 (d, J ) 9.0 Hz, 2 H), 8.00-8.04 (m, 1H); 13C NMR δ
21.2, 39.9, 67.5, 110.9, 112.2, 119.7, 123.6, 127.1, 128.4, 129.0,
129.8, 131.1, 131.3, 133.4, 139.0, 146.7, 153.9, 190.2. Anal.
Calcd for C23H22N4O: C, 74.56; H, 5.99; N, 15.13. Found: C,
74.38; H, 6.02; N, 15.18.
) 7.8 Hz, 2 H); 13C NMR δ 21.2, 126.4, 127.4, 127.8, 128.3,
128.4, 128.6, 129.4, 134.6, 137.5, 137.6.
tr a n s-1-P h en y1-1-n on en e (5b).29 Hexanes as eluent fol-
1
lowed by evaporation gave the product: oil; H NMR δ 0.89
(t, J ) 6.5 Hz, 3 H), 1.15-1.55 (m, 10 H), 2.20 (q, J ) 7.0 Hz,
2 H), 6.22 (dt, J ) 6.6, 15.9 Hz, 1 H), 6.38 (d, J ) 15.9 Hz, 1
H), 7.14-7.35 (m, 5 H); 13C NMR δ 14.1, 22.7, 29.2, 29.4, 31.9,
33.1, 125.9, 126.7, 128.4, 129.7, 131.2, 138.0.
tr a n s-1-(1-Na p h th yl)-4-m eth yl-1-p en ten e (5c). Hexanes
as eluent followed by evaporation gave the product: oil; 1H
NMR δ 0.99 (d, J ) 6.6 Hz, 6 H), 1.70-1.90 (m, 1 H), 2.15-
2.25 (m, 2 H), 6.21 (dt, J ) 15.5, 7.4 Hz, 1 H), 7.08 (d, J )
15.5 Hz, 1 H), 7.35-7.60 (m, 4 H), 7.73 (d, J ) 8.4 Hz, 1 H),
7.80-7.90 (m, 1 H), 8.12 (d, J ) 7.5 Hz, 1 H); 13C NMR δ 22.4,
28.6, 42.8, 123.6, 124.0, 125.6, 125.7, 125.8, 127.2, 128.1, 128.4,
131.2, 133.2, 133.6, 135.9. Anal. Calcd for C16H18: C, 91.37;
H, 8.63. Found: C, 91.60; H, 9.01.
tr a n s-1-Na p h th yl-3,3-d im eth yl-1-bu ten e (5d ). Hexanes
as eluent followed by evaporation gave the product: oil; 1H
NMR δ 1.21 (s, 9 H), 6.26 (d, J ) 15.9 Hz, 1 H), 7.04 (d, J )
15.9 Hz, 1 H), 7.25-7.56 (m, 4 H), 7.73 (d, J ) 8.4 Hz, 1 H),
7.81-7.85 (m, 1 H), 8.10-8.14 (m, 1 H); 13C NMR δ 29.7, 33.8,
121.9, 123.5, 124.0, 125.6, 125.7, 125.7, 127.1, 128.5, 131.4,
133.7, 136.0, 145.3. Anal. Calcd for C16H18: C, 91.37; H, 8.63.
Found: C, 91.61; H, 9.03.
r-[4-(Dim e t h yla m in o)p h e n yl]-r-(b e n zot r ia zol-1-yl)-
m eth yl 4-Meth ylp h en yl Keton e (4f). Crystallization of the
reaction mixture from hexane/ethyl acetate (1:1): mp 164-
165 °C; 1H NMR δ 2.41 (s, 3 H), 2.96 (s, 6 H), 6.67 (d, J ) 9.0
Hz, 2 H), 7.21-7.32 (m, 7 H), 7.80 (s, 1 H), 7.93 (d, J ) 8.1
Hz, 2 H), 8.02-8.05 (m, 1 H); 13C NMR δ 21.7, 40.0, 68.5, 112.0,
112.4, 119.6, 119.8, 123.5, 127.1, 129.1, 129.6, 130.3, 132.3,
133.5, 144.9, 146.7, 150.8, 192.9. Anal. Calcd for C23H22N4O:
C, 74.56; H, 5.99; N, 15.13. Found: C, 74.47; H, 6.18; N, 15.02.
r-(4-Meth ylph en yl)-r-(ben zotr iazol-1-yl)m eth yl 2-Th io-
p h en eyl Keton e (4g). Crystallization of the reaction mixture
1
from hexane/ethyl acetate (1:1): mp 104-107 °C; H NMR δ
2.34 (s, 3 H), 7.11 (t, J ) 4.5 Hz, 1 H), 7.20 (d, J ) 7.8 Hz, 2
H), 7.28-7.40 (m, 5 H), 7.67 (s, 1 H), 7.70-7.68 (m, 2 H), 8.00-
8.08 (m, 1 H); 13C NMR δ 21.2, 68.6, 111.6, 120.0, 123.9, 127.5,
128.6, 128.9, 130.0, 133.1, 133.9, 135.5, 139.6, 141.4, 146.7,
185.7. Anal. Calcd for C19H15N3OS: C, 68.45; H, 4.54; N, 12.61.
Found: C, 68.22; H, 4.38; N, 12.58.
tr a n s-p-Meth yl-p′-(dim eth ylam in o)stilben e (5e). CH2Cl2/
hexane (1:1) as eluent followed by evaporation gave the solid
1
product: mp 163-165 °C; H NMR δ 2.34 (s, 3 H), 2.97 (s, 6
H), 6.71 (d, J ) 9.0 Hz, 2 H), 6.88 (d, J ) 16.2 Hz, 1 H), 7.00
(d, J ) 16.2 Hz, 1 H), 7.13 (d, J ) 8.1 Hz, 2 H), 7.30-7.42 (m,
4 H); 13C NMR δ 21.2, 40.5, 112.5, 124.4, 125.9, 126.0, 127.4,
127.8, 129.3, 135.4, 136.4, 150.0. Anal. Calcd for C17H19N: C,
86.02; H, 8.07; N, 5.90. Found: C, 86.11; H, 8.45; N, 6.10.
tr a n s-1-(4-Met h ylp h en yl)-2-t h iop h en eylet h en e (5f).
Hexanes as eluent followed by evaporation gave the solid
product: mp 104-107 °C (lit.30 mp 115-6 °C); 1H NMR δ 2.36
(s, 3 H), 6.91 (d, J ) 16.2 Hz, 1 H), 6.99-7.02 (m, 1 H), 7.04-
7.08 (m, 1 H), 7.14-7.19 (m, 3 H), 7.20-7.26 (m, 1 H), 7.37 (d,
J ) 8.1 Hz, 2 H); 13C NMR δ 21.2, 120.9, 124.0, 125.7, 126.2,
127.5, 128.4, 129.4, 134.2, 137.5, 143.2. Anal. Calcd for
r-(4-Meth ylp h en yl)-r-(ben zotr ia zol-1-yl)m eth yl 2-(N-
Meth ylp ip er id in yl) Keton e (4h ) (a Mixtu r e of Tw o Dia -
ster eom er s). Silica gel column chromatography with CH2Cl2/
MeOH (100:5) as eluent followed by evaporation of the solvents
1
gave the solid product: mp 151-2 °C; H NMR δ 1.21-1.99
(m, 6 H), 2.01-2.42 (m, 7 H), 2.91-3.10 (m, 2 H), 7.02-7.42
(m, 8 H), 8.00-8.06 (m, 1 H). Anal. Calcd for C21H24N4O: C,
72.37; H, 6.95; N, 16.09. Found: C, 72.31; H, 7.09; N, 16.05.
Gen er a l P r oced u r e for Gen er a t in g t h e Low -Va len t
Tita n iu m . To a 250 mL three-neck flask under argon
protection was added Zn-Cu (5.4 g), and the system was
degassed and protected with argon. TiCl3 (3.85 g 15 mmol)
was quickly weighed and added to the flask, which was again
degassed and protected with argon. Under stirring, dry DME
(40 mL) was added with a syringe, and the mixture was
refluxed for 5 h and cooled to room temperature (with TiCl3/
Li, see ref 1).
C
13H12S: C, 77.97; H, 6.04. Found: C, 77.71; H, 6.19.
1-p-Tolyl-2-[2-(N-m eth ylp ip er id in yl)]eth en e (5g). Alu-
minum oxide (activated, neutral, 50-200 µm) with hexane/
ethyl acetate (1:1) as eluent followed by evaporation gave the
product: oil; 1H NMR (cis- and trans-isomers) δ 1.20-1.83 (m,
6 H, cis and trans), 1.90-2.08 (m, 1 H, cis and trans), 2.20 (s,
3 H, cis), 2.24 (s, 3 H, trans), 2.33 (s, 3 H, trans), 2.35 (s, 3 H,
cis), 2.40-2.50 (m, 1 H, cis and trans), 2.80-3.00 (m, 1 H, cis
and trans), 5.6 (dd, J ) 12, 9.8 Hz, 1 H, cis), 6.1 (dd, J ) 15.9,
8.7 Hz, 1 H, trans), 6.40-6.50 (m, 1 H, cis and trans), 7.0-7.3
(m, 4 H, cis and trans); 13C NMR δ (cis- and trans-isomers)
21.1, 23.8, 24.0, 26.0, 29.7, 32.5, 33.5, 44.3, 44.6, 44.7, 56.3,
56.5, 61.8, 68.1, 126.1, 128.6, 128.8, 129.2, 129.4, 130.4, 132.7,
134.4, 134.6, 135.6, 136.3, 137.0. Anal. Calcd for C15H21N: N,
6.51. Found: N, 6.72.
P r oced u r e for th e P r ep a r a tion of 5h . 1-(Benzotriazol-
1-yl)-3-methyl-2-butene (1e) (0.90 g, 4.8 mmol) was dissolved
in dry THF (30 mL) in a lithiation bottle protected under argon
or nitrogen, and the mixture was cooled to -78 °C. A solution
of n-BuLi (3.3 mL of 1.6 M in hexane, 5.3 mmol) was added.
After 15 min, methyl 2-methyl-3-furancarboxylate (3h ) (0.74
g, 5.3 mmol) in dry THF (4 mL) was added dropwise. After
the color disappeared (within about 5 min), the reaction was
quenched with water (30 mL) followed by addition of NaBH4
(0.8 g). The mixture was warmed and maintained at 40 °C
for 1 h. Ether (100 mL) was added, and the organic phase
was separated and dried with MgSO4. After evaporation of
the solvents, the residue was dried in a vacuum, protected
under argon, and transferred with a syringe using dry DME
(2 × 15 mL) to the low-valent titanium mixture. The reaction
Gen er a l P r oced u r e for Olefin a tion 5a -g. R-(Benzotri-
azol-1-yl) ketone 4a -h (5 mmol) was heated at 40 °C for 15
min with NaBH4 (0.5 g) in ethanol (40 mL), and the reaction
mixture was then cooled to room temperature. The reaction
mixture was then slowly poured into saturated NH4Cl solution
(50 mL). CH2Cl2 (100 mL) was added, and the mixture was
stirred vigorously for 5 min. The organic phase was separated,
washed with 5% NaCl solution (50 mL) and water (50 mL),
and dried with MgSO4. Hexane (20 mL) was added, the
solution was rotovapored, and the residue was dried under
vacuum to give the corresponding intermediate 6 as a mixture
of diastereomers. Mixture 6 was dissolved in DME (20 mL)
and then added to the low-valent titanium mixture (generated
as described above), and the mixture was refluxed overnight.
It was then cooled to room temperature and filtered, and the
solid residue was extracted with CH2Cl2 (2 × 100 mL). The
combined organic phase was washed with saturated NH4Cl
(100 mL), 10% Na2CO3 solution (100 mL), and water (100 mL)
and dried with MgSO4. Evaporation of the solvent followed
by column chromatography (for eluents, see each compound
below) gave 5a -g.
tr a n s-1-P h en yl-2-(p-t olu yl)et h ylen e (5a ). Hexanes as
eluent followed by evaporation gave the solid product: mp
1
119-120 °C (lit.28 mp 119-120 °C); H NMR δ 2.35 (s, 3 H),
7.07 (s, 2 H), 7.16 (d, J ) 8.1 Hz, 2 H), 7.22-7.27 (m, 1 H),
7.34 (t, J ) 7.8 Hz, 2 H), 7.41 (d, J ) 8.1 Hz, 2 H), 7.49 (d, J
(29) Kauffmann, T.; Rauch, E.; Schulz, J . Chem. Ber. 1973, 106,
1612.
(30) Arcoria, A.; Fisichella, S.; Scarlata, G.; Torre, M. J . Heterocycl.
Chem. 1973, 643.
(28) Asokan, C. V.; Ila, H.; J unjappa, H. Synthesis 1987, 284.

3444 J . Org. Chem., Vol. 63, No. 10, 1998
Katritzky et al.
mixture was refluxed for 2 h, cooled to room temperature, and
filtered, and the solid residue was extracted with ether (2 ×
100 mL). The combined organic phase was washed with
saturated NaHCO3 (2 × 100 mL), brine (100 mL), and water
(100 mL) and dried with MgSO4. Evaporation of the solvent
followed by silica gel column chromatography with hexane/
ethyl acetate (1:1) as the eluent gave the product 5h as an oil:
1H NMR δ 1.84 (s, 6 H), 2.31 (s, 3 H), 5.96 (d, J ) 10.8 Hz, 1
H), 6.24 (d, J ) 15.3 Hz, 1 H), 6.50 (d, J ) 1.5 Hz, 1 H), 6.60
(dd, J ) 10.8, 15.3 Hz, 1 H), 7.24 (d, J ) 1.8 Hz, 1 H); 13C
NMR δ 11.7, 18.4, 26.1, 107.8, 119.2, 119.7, 124.3, 125.5, 134.4,
140.7, 148.9. Anal. Calcd for C11H14O: C, 81.43; H, 8.70.
Found: C, 81.66; H, 9.10.
NMR δ 1.22 (d, J ) 6.3 Hz, 3 H), 1.92 (br s, 2 H), 3.60-3.66
(m, 1 H), 6.17 (dd, J ) 6.6, 15.9 Hz, 1 H), 6.43 (d, J ) 15.9 Hz,
1 H), 7.10-7.40 (m, 5 H); 13C NMR δ 23.7, 49.3, 126.2, 127.2,
128.0, 128.5, 135.7, 137.0.
S-tr a n s-1-p-Tolyl-3-a m in o-4-p h en yl-1-bu ten e (13b): oil;
[R]22 +37.9° (c 1.01, CHCl3); 1H NMR δ 1.40 (br s, 2 H), 2.32
D
(s, 3 H), 2.68 (dd, J ) 8.1, 13.5 Hz, 1 H), 2.90 (dd, J ) 5.1,
13.5 Hz, 1 H), 3.72-3.76 (m, 1 H), 6.21 (dd, J ) 6.9, 15.8 Hz,
1 H), 6.46 (d, J ) 15.8 Hz, 1 H), 7.00-7.40 (m, 9 H); 13C NMR
δ 21.1, 44.6, 55.1, 126.1, 126.3, 128.3, 128.8, 129.2, 129.4, 132.9,
134.2, 137.0, 138.6; HRMS calcd for C17H19N m/e 237.1517,
found 237.1496.
R-tr a n s-1-(4-ter t-Bu t ylfu r a n -2-yl)-3-a m in o-1-b u t en e
1
Gen er a l P r oced u r e for P r ep a r a tion of N-P r otected
E st er s 9a -c. To R-amino acid methyl ester hydrochloride
7a -c (20 mmol) in a three-neck round-bottom flask under
argon was added NEt3 (6.16 g, 61 mmol) with dry CH2Cl2 (15
mL), and the mixture was cooled to 0 °C. 1,2-Bis(chlorodi-
methylsilyl)ethane (8) (4.73 g, 22 mmol, 96%) was added
dropwise with dry CH2Cl2 (15 mL). The mixture was stirred
at 40 °C for 1 h, diluted with hexane, and filtered. The filtrate
was evaporated and dried in a vacuum. Hexane was added
to the residue followed by filtration with a fine sintered glass
filter to obtain a clear solution that was then subjected to
evaporation under vacuum to give a clear oil 9a -c (>92%).
Gen er a l P r oced u r e for P r ep a r a tion of P r im a r y Allyl-
a m in es 13a -e. Compound 1 (6.4 mmol) was dissolved in dry
THF (30 mL) in a lithiation bottle protected under argon or
nitrogen, and the mixture was cooled to -78 °C. A solution
of n-BuLi (4.4 mL of 1.6 M in hexane, 7.0 mmol) was added.
After 15 min, the N-protected ester 9 (7.0 mmol) (prepared as
described above) in dry THF (4 mL) was added dropwise (and
then the temperature was raised to about 0 °C for entry 5,
Table 2). After the color disappeared, the reaction mixture
was quenched with water (30 mL), followed by addition of
NaBH4 (0.9 g). The mixture was warmed and maintained at
40 °C for 1 h. Ether (100 mL) was added, and the organic
phase was separated and dried with K2CO3. After evaporation
of the solvents, the residue was dried in a vacuum, protected
under argon, and transferred with dry DME (2 × 15 mL) to
the low-valent titanium mixture. The reaction mixture was
refluxed for 2 h and decanted to a sintered glass filter. Both
the filtrate and the solid residue were quenched with 15%
KOH solution (100 mL), and the aqueous mixture was ex-
tracted with solvents (100 mL, 2 × 50 mL, 1:1 ethyl acetate
and ether for the DME filtrate; ether for the solid residue).
(Moderate stirring for 10-15 min is recommended for extrac-
tion instead of vigorous shaking to obtain good separation. In
case phase separation is hard to complete, filtration can be
used to solve the problem.) The organic phases were combined,
dried with K2CO3, and subjected to evaporation. The residue
was diluted with ether (20 mL) and treated with 1 M HCl
ethanol solution (20 mL). After being stirred for 1 h, the
mixture was basified with saturated K2CO3 solution (50 mL).
CH2Cl2 (100 mL) was added, and the organic phase was
separated and dried with K2CO3. Column chromatography of
the residue (first 100:5 CH2Cl2 and MeOH to elute other
fractions and then 100:5:1 CH2Cl2, MeOH, and NEt3 to fully
rinse out the products) gave products 13a -e.
(13c): oil; [R]22 +3.2° (c 1.21, CHCl3); H NMR δ 1.16-1.23
D
(m, 12 H), 1.69 (br s, 2 H), 3.55-3.65 (m, 1 H), 6.11 (dd, J )
6.3, 15.9 Hz, 1 H), 6.17 (s, 1 H), 6.24 (d, J ) 15.9 Hz, 1 H),
7.07 (s, 1 H); 13C NMR δ 23.8, 30.7, 45.2, 48.9, 106.9, 116.6,
134.6, 135.9, 137.8, 152.6. Anal. Calcd for C12H19NO: N, 7.25.
Found: N, 7.64.
S -t r a n s-2-Me t h yl-6-a m in o-7-p h e n yl-2,4-h e p t a d ie n e
(13d ): oil; [R]22 +36.6° (c 0.99, CHCl3); 1H NMR δ 1.20 (br s,
D
2 H), 1.75 (s, 3 H), 1.78 (s, 3 H), 2.61 (dd, J ) 8.3, 13.4 Hz, 1
H), 2.87 (dd, J ) 5.1, 13.2 Hz, 1 H), 3.60-3.70 (m, 1 H), 5.60
(dd, J ) 6.9, 15.0 Hz, 1 H), 5.82 (d, J ) 10.5 Hz, 1 H), 6.37
(dd, J ) 10.8, 15.0 Hz, 1 H), 7.20-7.40 (m, 5 H); 13C NMR δ
18.2, 25.9, 44.8, 54.9, 124.5, 125.7, 126.2, 128.3, 129.3, 134.8,
138.9; HRMS calcd for C14H19N m/e 201.1517, found 201.1543.
tr a n s,tr a n s-1-P h en yl-5-am in o-1,3-pen tadien e (13e): oil;
1H NMR δ 1.53 (br s, 2 H), 3.41 (d, J ) 5.7 Hz, 2 H), 5.92 (dt,
J ) 15.3, 6.0 Hz, 1 H), 6.32 (dd, J ) 10.5, 15.3 Hz, 1 H), 6.50
(d, J ) 15.6 Hz, 1 H), 6.79 (dd, J ) 10.5, 15.6 Hz, 1 H), 7.15-
7.45 (m, 5 H); 13C NMR δ 44.0, 126.2, 127.3, 128.5, 128.6, 130.0,
131.5, 135.5, 137.3. Anal. Calcd for
Found: N, 8.53.
C11H13N: N, 8.80.
P r ep a r a t ion of L-tr a n s-1-(2-P yr r olid in yl)-2-p h en yl-
eth en e (19). Ester 15 was prepared in a similar way to 9
except that only 2.05 equiv of NEt3 was used. The procedure
for the preparation of 19 is similar to that of 13 except that
NEt3 (2 mL, corresponding to 6.6 mmol scale) was present in
the low-valent titanium mixture and there was no HCl/ethanol
treatment: oil; [R]22D -64.5° (c 1.28, CHCl3); 1H NMR δ 1.50-
1.70 (m, 1 H), 1.71-1.95 (m, 2 H), 1.96-2.15 (m, 1 H), 2.50
(br s, 1 H), 2.85-3.04 (m, 1 H), 3.06-3.20 (m, 1 H), 3.60-3.80
(m, 1 H), 6.23 (dd, J ) 7.2, 15.9 Hz, 1 H), 6.53 (d, J ) 15.9 Hz,
1 H), 7.10-7.50 (m, 5 H); 13C NMR δ 25.2, 32.3, 46.4, 60.9,
126.2, 127.2, 128.4, 129.7, 132.4, 137.1; HRMS calcd for
C
12H15N m/e 173.1205, found 173.1206.
Ack n ow led gm en t . We thank Professor Tomas
Hudlicky’s group for help in determining enantiomeric
excess, Ms. Clara Fali for providing starting material
1f, and Dr. David Ager for helpful discussions.
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compounds 5g, 13a -e, and 19 are provided (24
pages). This material is contained in libraries on microfiche,
immediately follows this article in the microfilm version of the
journal, and can be ordered from the ACS; see any current
masthead page for ordering information.
R-tr a n s-1-P h en yl-3-a m in o-1-bu ten e (13a ): oil; [R]22
D
+25.8° (c 1.16, CHCl3) [lit.14a [R]22 +25.9° (c 0.9, CHCl3)]; 1H
J O971546F
D