Stereoselective alkylation of chiral 2-imidoylphenols with organolithium reagents: Synthesis of enantiopure 2-aminoalkylphenols

Article abstract of DOI:10.1021/jo020423e

In this paper the addition of organolithium reagents to chiral imidoylphenols to prepare enantiopure phenolic Mannich-type bases is described. The experimental data show that this kind of imine is surprisingly reactive toward organolithium reagents, differently from classical imines, and does not need any Lewis acid or base activation. Moreover, interesting results have been obtained with aldimines but more unusually with ketimines. This reaction results in high yields and diastereoselectivities and allows the preparation of aminophenols quaternary at the C-1 carbon atom, which cannot be prepared with the methods available till now. The sense of asymmetric induction has been explained and confirmed in agreement with the results previously obtained by hydride reduction of the same substrates. In some cases this procedure is complementary to the reductive one, allowing the preparation of the diastereomers less abundant in the reduction. The reaction allows the synthesis of one or the other of the two diastereomers, choosing the opportune starting imidoylphenol and the organolithium reagent.

Full text of DOI:10.1021/jo020423e

Ster eoselective Alk yla tion of Ch ir a l 2-Im id oylp h en ols w ith
Or ga n olith iu m Rea gen ts: Syn th esis of En a n tiop u r e
2-Am in oa lk ylp h en ols
Cristina Cimarelli, Gianni Palmieri,* and Emanuela Volpini
Dipartimento di Scienze Chimiche via s. Agostino 1-62032 Camerino, Italy
gianni.palmieri@unicam.it
Received J une 21, 2002
In this paper the addition of organolithium reagents to chiral imidoylphenols to prepare enantiopure
phenolic Mannich-type bases is described. The experimental data show that this kind of imine is
surprisingly reactive toward organolithium reagents, differently from classical imines, and does
not need any Lewis acid or base activation. Moreover, interesting results have been obtained with
aldimines but more unusually with ketimines. This reaction results in high yields and diastereo-
selectivities and allows the preparation of aminophenols quaternary at the C-1 carbon atom, which
cannot be prepared with the methods available till now. The sense of asymmetric induction has
been explained and confirmed in agreement with the results previously obtained by hydride
reduction of the same substrates. In some cases this procedure is complementary to the reductive
one, allowing the preparation of the diastereomers less abundant in the reduction. The reaction
allows the synthesis of one or the other of the two diastereomers, choosing the opportune starting
imidoylphenol and the organolithium reagent.
SCHEME 1. En a n tioselective Ca ta lyzed Alk yla tion
of Ald eh yd es w ith Or ga n ozin c Rea gen ts
In tr od u ction
The development of efficient enantioselective catalysts
applicable to a wide range of reactions represents an
important challenge in synthetic organic chemistry.1
In previous works it was found that a catalytic amount
of enantiopure aminoalkylphenols 3 and aminoalkyl-
naphthols 4 considerably accelerates the addition of
dialkylzincs to aldehydes, affording the corresponding
alcohol 2 in good enantiomeric purity2 (see Scheme 1).
The precatalyst aminophenols 3, known also for their
potential utility as pharmaceuticals, insect growth regu-
lators, sterilants, and photochromic and thermochromic
* To whom correspondence should be addressed. Fax: (+39) 0737
637345.
molecules,3 are very accessible compounds, generally
obtained by stereoselective reduction of the corresponding
2-imidoylphenols.2a,b,4 On the other hand, the aminoalky-
(1) (a) Berrisford, D. J .; Bolm, C.; Sharpless, K. B. Angew. Chem.,
Int. Ed. Engl. 1995, 34, 1059-1070. (b) Soai, K.; Niwa, S. Chem. Rev.
1992, 92, 833-856. (c) Kitamura, M.; Okada, S.; Suga, S.; Noyori, R.
J . Am. Chem. Soc. 1989, 111, 4028-4036. (d) J uaristi, E.; Escalante,
J .; Leo`n-Romo, J . L.; Reyes, A. Tetrahedron: Asymmetry 1998, 9, 715-
740. (e) Rijnberg, E.; Hovestad, N. J .; Kleij, A. W.; J astrzebski, J . T.
B. H.; Boersma, J .; J anssen, M. D.; Spek, A. L. and van Koten, G.
Organometallics 1997, 16, 2847-2857. (f) Nakano, H.; Kumagai, N.;
Matsuzaki, H.; Kabuto, C.; Hongo, V. Tetrahedron: Asymmetry 1997,
8, 1391-1401. (g) Watanabe, V.; Araki, V.; Butsugan, V. J . Org. Chem.
1991, 56, 2218-2224. (h) Kitamura, M.; Suga, S.; Kawai, K.; Noyori,
R. J . Am. Chem. Soc. 1986, 108, 6071-6072. (i) Hayase, T.; Sugiyama,
T.; Suzuki, M.; Shibata, T.; Soai, K. J . Fluorine Chem. 1997, 1-5. (j)
Sola`, L.; Reddy, K. S.; Vidal-Ferran, A.; Moyano, A.; Perica`s, M. A.;
Riera, A.; Alvarez-Larena, A.; Piniella, J . F. J . Org. Chem. 1998, 63,
7078-7082. (k) Gibson, C. L. Tetrahedron: Asymmetry 1999, 10, 1551-
1561. (l) Iuliano, A.; Pini, D.; Salvadori, P. Tetrahedron: Asymmetry
1995, 6, 739-744. (m) Hayashi, M.; Kaneko, T.; Ognuni, N. J . Chem.
Soc., Perkin Trans. 1 1991, 25-28. (n) Noyori, R. Asymmetric Catalysis
in Organic Synthesis; J ohn Wiley: New York, 1994. (o) Knochel, P. In
Comprehensive Organic Synthesis; Trost, B. M., Ed.; Pergamon Press:
Elmsford, NY, 1991; pp 211-229. (p) Kitamura, M.; Suga, S.; Oka,
H.; Noyori, R. J . Am. Chem. Soc. 1998, 120, 9800-9809. (q) Yamakawa,
M.; Noyori, R. J . Am. Chem. Soc. 1995, 117, 6327-6335.
(2) (a) Palmieri, G. Eur. J . Org. Chem. 1999, 805-811. (b) Palmieri,
G. Tetrahedron: Asymmetry 2000, 11, 3361-3373. (c) Cardellicchio,
C.; Ciccarella, G.; Naso, F.; Perna, F.; Tortorella, P. Tetrahedron 1999,
55, 14685-14692. (d) Liu, D. X.; Zhang, L. C.; Wang, Q.; Da, C. S.;
Xin, Z. Q.; Wang, R.; Choi, M.; Chan, A. Org. Lett. 2001, 3, 2733-
2735.
(3) (a) Barlin, G. B.; Ireland, S. J .; Nguyen, T. M. T.; Kotecka, B.;
Rieckmann, K. H. Aust. J . Chem. 1994, 47, 1143. (b) Barlin, G. B.;
Ireland, S. J .; Nguyen, T. M. T.; Kotecka, B.; Rieckmann, K. H. Aust.
J . Chem. 1994, 47, 1533. (c) J urd, L.; Fye, R. L.; Morgan, J . J . Agric.
Food Chem. 1979, 27, 1007. (d) Langley, P. A.; Trewern, M. A.; J urd,
L. Bull. Entomol. Res. 1982, 72, 473. (e) J urd, L. J . Heterocycl. Chem.
1985, 22, 993. (f) Komissarov, V. N.; Ukhin, L. Y.; Kharlanov, V. A.;
Lokshin, V. A.; Bulgarevich, E. Y. Bull. Acad. Sci. USSR, Div. Chem.
Sci. 1992, 41, 1875.
(4) (a)Cimarelli, C.; Palmieri, G. Tetrahedron: Asymmetry 2000, 11,
2555-2563. (b) Cimarelli, C.; Palmieri, G.; Volpini, E. Tetrahedron
2001, 57, 6089-6096. (c) Cimarelli, C.; Palmieri, G. Tetrahedron 1998,
54, 15711-15720.
10.1021/jo020423e CCC: $25.00 © 2003 American Chemical Society
Published on Web 01/25/2003
1200
J . Org. Chem. 2003, 68, 1200-1206

Alkylation of Chiral 2-Imidoylphenols
TABLE 1. Ster eoselective Ad d ition of Or ga n olith iu m Rea gen ts to Ch ir a l Im in es (R)-5a -f
method Aa
method Ba
dr
entry
(R)-5
R
R1
6b
yield c (%)
dr
de
yieldc (%)
97
de
52
1
2
(R)-5a
(R)-5a
H
H
Me
Bu
(R,R)-6a a 4a
(R,R)-6a b
95
94
69/31
68/32
73/27
76/24
65/35
61/39
55/45
63/37
90/10
87/13
98/2
52/48
87/13
78/22
98/2
86/14
63/37
77/23
71/29
59/41
38
36
46
52
30
22
10
26
80
74
96
4
74
56
96
72
26
54
42
18
24/76
92d (62)
68
3
4
5
6
7
8
9
(R)-5b
(R)-5c
(R)-5c
(R)-5c
(R)-5c
(R)-5d
(R)-5d
Me
H
H
H
H
Bu
Me
Bu
Ph
t-Bu
Bu
Ph
(R,R)-6bb
(1S,1R)-6ca 2a
(R,R)-6cb
98
98
96
95
98
96 (49)
98 (58)
74/26
62/38
70/30
48
24
40
(1S,1R)-6cc2a
(R,R)-6cd 2a
(1S,1R)-6d b
(1S,1R)-6d c
Me
Me
98
94 (79)
90 (81)
95/5
99/1
90
98
94
90d
80e
95
10
11
12
(R)-5d
(R)-5e
(R)-5e
Me
Et
Et
t-Bu
Me
Bu
(1S,1R)-6d d
(R,R)-6e a
(1S,1R)- 6eb
81 (63)
96 (68)
86/14
79/21
72
58
96
79d (69)
94
13
14
15
16
17
(R)-5e
(R)-5e
(R)-5f
(R)-5f
(R)-5f
Et
Et
Ph
Ph
Ph
Ph
(1S,1R)-6ec
(1S,1R)-6ed
(R,R)-6fa
(R,R)-6fb
(1S,1R)-6fd
t-Bu
Me
Bu
93e
23e
85e
80e
81 (61)
72 (39)
81/19
61/39
62
22
t-Bu
a
Method A: R1Li (3.5 equiv), n-hexane, 0-40 °C, 1-4 h. Method B: R1Li (3.5 equiv), TMEDA (3.5 equiv), toluene, 0 °C to rt, 15-60
b
min. Major diastereomer. In the numbering of compound 6, the first letter derives from the starting imidoylphenol 5 while the second
one shows the organolithium reagent used. c Combined yields of the two diastereomers isolated. The yields of the isolated pure major
diastereomer are given in parentheses. Reaction performed at - 70 °C for 1 h. e Reaction performed at 40 °C for 1-3 h.
d
SCHEME 2. Mech a n ism Hyp oth esis for th e
Ster eoselective Alk yla tion of th e Im in es (R)-5a ,b
a n d Im id oylp h en ols (R)-5c-f
lation of electron-rich aromatic compounds (the aromatic
Mannich reaction) is an alternative route to aminonaph-
thols 4 which have catalytic properties similar to those
of aminoalkylphenols.2b,5Anyway, all these reactions af-
ford only methylene or methine C-1 carbon atom prod-
ucts. The search for quaternary C-1 carbon atom ami-
noalkylphenols prompted us to explore a new synthetic
strategy for their preparation.
The diastereoselective addition of organometallic re-
agents to the CdN bond of chiral 2-imidoylphenol 5
appears to be an alternative appealing route to obtain
enantiomerically pure quaternary C-1 carbon atom ami-
noalkylphenols 6. In fact, it is known that the diastereo-
selective addition of organometallic reagents to imines
is one of the key methods for preparing various amines.6
The addition of organometallic reagents to ketimines
is not widely reported because imines have a propensity
to enolize. Enolizable ketimines are generally inert to
organometallic reagents and undergo complete enoliza-
tion in their presence. Therefore, the majority of the
literature in this field addresses the addition of organo-
metallic reagents to aldimines, but not to ketimines.
Moreover, an additional challenge to this approach is that
In this paper, we report the results of our work on the
imines tend to have poor reactivity toward nucleophilic
diastereoselective addition of organolithium reagents to
addition and are often activated by the presence of a
chiral 2-imidoylphenols, in which chiral 1-phenylethyl-
Lewis acid or by the presence of bases such as TMEDA
amine is used as a convenient chiral auxiliary (see
or (-)-sparteine6c,f,g or through substitution of nitrogen
Scheme 2). Due to the intramolecular hydrogen bond, the
with activating groups such as N-acyliminium ions and
starting chiral 2-imidoylphenols 5c-f are stable materi-
nitrones.
als, very accessible, and easily prepared in high yields
from (R)-1-phenylethylamine and the required o-acyl-
(5) Cimarelli, C.; Mazzanti, A.; Palmieri, G.; Volpini, E. J . Org.
Chem. 2001, 66, 4759-4765.
(6) (a) Yamamoto, Y.; Nishii, S.; Maruyama, K.; Komatsu, T.; Ito,
phenols under solventless conditions.7
W. J . Am. Chem. Soc. 1986, 108, 7778-7786. (b) Boga, C.; Savoia, D.;
Umani-Ronchi, A. Tetrahedron: Asymmetry 1990, 1, 291-294. (c)
Denmark, S. E.; Nakajima, N.; Nicaise, O. C. J . Am. Chem. Soc. 1994,
116, 8797-8798. (d) Enders, D.; Reinhold, U. Tetrahedron: Asymmetry
1997, 8, 1895-1946. (e) Bloch, R. Chem. Rev. 1998, 98, 1407-1438.
(f) Yamada, H.; Kawate, T.; Nishida, A.; Nakagawa, N. J . Org. Chem.
1999, 64, 8821-8828. (g) Arrasate, S.; Lete, E.; Sotomayor, N.
Tetrahedron: Asymmetry 2001, 12, 2077-2082.
Resu lts a n d Discu ssion
The results of the diastereoselective alkylation of
aldimine (R)-5a ,c, reported in Table 1, are good, but even
(7) Boga, C.; Di Martino, E.; Forlani, L.; Torri, F. J . Chem. Res.,
Miniprint 2001, 219-235.
J . Org. Chem, Vol. 68, No. 4, 2003 1201

Cimarelli et al.
better de’s were observed with ketimines (R)-5d -f (up
to 96% de).
The alkylation is fast in all the reactions with high
yields under both conditions (methods A and B), with the
exception in the case of the preparation of (R,R)-6fa (23%
yield with method A). The reactions were performed with
the same good results in n-hexane or toluene, solvents
with low coordinating ability for organolithium reagents.
In THF the alkylation reaction does not occur. The use
of the bulkier 1-naphthylethylamine as chiral auxiliary
does not improve the asymmetric induction, and the
results are the same using 1-phenylethylamine (1-naph-
thylethylamine imidoylphenols of 2-hydroxybenzaldehyde
and 2-hydroxyacetophenone, treated with butyllithium
according to method A, gave de’s of 20% and 80%,
respectively). Generally better yields and de’s were
obtained with the use of TMEDA, but good results are
obtained in several entries even in the absence of it. The
(-)-sparteine serves effectively as the external ligand,
showing a dramatic effect on the alkylation of aldimines
with alkyllithium (ee up to 91%) as reported in the
literature.6c,f,g We have observed that, by using the (-)-
sparteine in stoichiometric quantities in the alkylation
of (R)- and (S)-5c with methyllithium, the same low
diastereoselectivity (de ) 41%) with both enantiomers
of the starting material was obtained, showing any
participation of the (-)-sparteine in the reaction. The fast
alkylation also in the absence of TMEDA and the lack of
effects of the (-)-sparteine on the reaction allow one to
hypothesize that the first step of this reaction is the
chelation of substrate on a lithium atom, forming the
intermediate (R)-5-Li. It is more reactive than the
starting material toward the nucleophilic alkylation,
which occurs intramolecularly through the transition
state Si-6-TS (see Scheme 2). Therefore, the alkylation
proceeded smoothly also in the case of ketimines to give
the Si-6c-f diastereomers predominantly. The best di-
astereoselectivities are obtained in the synthesis of
aminophenols 6d b,d c,ea ,ec. With a lowering of the
reaction temperature (-70 °C) as in entries 2, 9, 12, the
reaction is still fast and the products show a higher
diastereoselectivity, but a consequent lowering of the
yields was observed. As seen in Scheme 2 and Table 1,
in the case of imine (R)-5a ,b the nucleophilic addition of
the organolithium reagent takes place preferentially on
the Re diastereotopic face of the imine. Conversely, in
the case of imidoylphenols (R)-5c-f the alkylation occurs
preferentially on the Si face of the imine function. This
asymmetric induction is the same as that observed in the
reduction of the imidoylphenols, where the intramolecu-
lar transfer of the hydride occurs preferentially on the
less hindered Si face of the imine function.2a,4a Unique
exceptions are the cases of the aminophenols 6-cb,cd ,fd ,
where the major diastereomer obtained was derived from
the alkylation on the Re face. Moreover, the exchange of
R with R1 on the starting imidoylphenol and on the
alkyllithium reagent allows one or the other of the two
possible diastereomers to be obtained as the major
product (entries 9 and 15). This stereoconvergent syn-
thesis is a confirmation of the hypothesized mechanism
of the asymmetric induction.
F IGURE 1. The more stable conformation for the aminophe-
nol (1S,1′R)-6d d (PM3 semiempirical level minimization12
)
with the indication of the shielding effect and NOE observed.
Ster eoch em istr y
1
The diastereomeric ratio was determined by H NMR
analysis of the amines 6 before and/or after purification.
1
Generally, the H NMR spectra of these diastereomeric
mixtures show the signals of the two methine protons
H-1 and H-1′ of the (R,R) diastereomers at higher fields
than those of the corresponding protons of the (S,R)
diastereomers.2,5,6f,8 The configurations of the aminophe-
nols (R,R)-6ca -cd were attributed to the 1H NMR
shielding effects, caused by the Ph-1′ group, on the
benzylic hydrogen H-1,9 in agreement with the most
stable conformation obtained with the semiempirical
minimization (PM3),12 or X-ray diffraction on analogous
structures.2d,5,8 Analogously, for o-aminophenols 6d b -
fd , with a quaternary C-1 carbon atom, the conforma-
tional analysis, with a systematic search procedure (PM3
semiempirical level minimization),12 has revealed the
preferred more stable conformation reported in Figure
1. Also in this conformation the Ph-1′ group causes a
shielding effect on the C-1 group under it,9 allowing the
1H NMR data of these products to be explained too.
On the basis of these considerations, NOE 1H NMR
experiments were carried out on the o-aminophenols
(1S,1′R)-6d b,d d and (R,R)-6ea to have experimental
confirmation of configuration and conformation attribu-
tions. Inversion of the H-1′ quartet lines enhances the
geminal Me-1′ and both the alkyl groups at the C-1
carbon atom signals, validating the results obtained by
conformational analysis.
Asym m etr ic In d u ction
The sense of asymmetric induction observed in the
alkylation of the imine (R)-5a can be rationalized through
a cyclic transition state, Re,Z-6a a -TS (see Figure 2a).
After the preliminary formation of a complex between
the σ-donor E-imine and alkyllithium, an E to Z isomer-
ization occurs to the more stable Z-5a -Li followed by the
(8) Cimarelli, C.; Palmieri, G.; Volpini, E. Org. Prep. Proced. Int.
2001, 33, 369-371.
(9) Harada, N.; Watanabe, M.; Kuwahara, S.; Sugio, A.; Kasai, Y.;
Ichikawa, A. Tetrahedron: Asymmetry 2000, 11, 1249-1253.
1202 J . Org. Chem., Vol. 68, No. 4, 2003

Alkylation of Chiral 2-Imidoylphenols
SCHEME 3. Exp er im en ta l Evid en ce (a ) a n d
Mech a n ism Hyp oth esis (b) for th e Ep im er iza tion
of th e Am in op h en ol 6cd
F IGURE 2. The hypothetical more stable Re and Si transition
structures for the alkylation of (a) the imine (R)-5a and (b)
the imidoylphenol (R)-5c (PM3 semiempirical level minimiza-
tion12).
substrates and the particular reactivity of these sub-
strates toward the nucleophiles used, due to the role of
the oxygen atom in the reaction mechanism.
carbon-carbon bond forming step.6f,10 The diastereo-
selectivity is dictated by the orientation of the auxiliary
group; the nucleophile attacks preferentially the Re less
hindered π face of the imine. The alternative Si,E- and
Re,E-6a a -TS transition states are more unstable than
the Re,Z-6a a -TS one (see Figure 2a).
A unique exception to this kinetic control was observed
for the case of aminophenols 6cb,cd ,fd , where the
thermodynamically more stable (R,R)-6cb,cd and (1S,1′R)-
6fd are the predominant diastereomers obtained in the
reaction. In particular, monitoring the synthesis of the
aminophenol 6cd , following the progress of the reaction
by 1H NMR of the reaction mixture aliquot, it is possible
to see an initial predominant presence of the kinetically
favorite (1S,1′R)-6cd (de ) 8%, starting reaction tem-
perature -40 °C). When the temperature was allowed
to rise slowly to 40 °C, the complete conversion was
observed with the final predominant formation of the
thermodynamically more stable (R,R)-6cd (de ) 26%).
The hypothesis of the reversibility of the alkylation
reaction was ascertained by the experiments shown in
the Scheme 3a.
The imines (R)-5c-f, capable of acting as bidentate
ligands toward lithium ion, react with the organolithium
reagents to form reactive imine complexes, e.g., (R)-5-
Li. The bridged lithium atom, coordinated to oxygen and
nitrogen atoms, activates the imine function toward the
nucleophilic addition, forming a rigid six-membered ring
and constraining the imine function in the E-configura-
tion. Successively, the complex (R)-5-Li should coordinate
a second molecule of organolithium reagent and convert
to the amine 6ca through a six-membered cyclic transi-
tion state, Si-6ca -TS, more stable than Re-6ca -TS10,11
(see Figure 2b). This consideration explains both the
sense of asymmetric induction for the alkylation of these
While (R,R)-6cd is stable in the presence of BuLi,
(1S,1′R)-6cd partially eliminates t-BuLi to the interme-
diate (R)-5c-Li, which adds BuLi to 6cb-Li2 (see Scheme
3b).
(10) Pratt, L. M.; Khan, I. M. Tetrahedron: Asymmetry 1995, 6,
2165-2176.
Con clu sion
(11) (a) Hashimoto, Y.; Kobayashi, N.; Kai, A.; Saigo, K. Synlett
1995, 961-962. (b) Alvaro, G.; Pacioni, P.; Savoia, D. Chem.sEur. J .
1997, 3, 726-731. (c) Bartoli, G.; Cimarelli, C.; Marcantoni, E.;
Palmieri, G.; Petrini, M. J . Chem. Soc., Chem. Commun. 1994, 715-
716. (d) Alvaro, G.; Savoia, D.; Valentinetti, M. R. Tetrahedron 1996,
52, 12571-12586.
(12) Semiempirical PM3 calculations were performed with Spartan
5.0.3, Wavefunction, Inc., 18401 Von Karmen Ave., No. 370, Irvine,
CA 92715.
In summary, addition of organolithium reagents to
chiral imidoylphenols to prepare enantiopure phenolic
Mannich-type bases was explored, which resulted in a
high-yielding and quite fast reaction. Owing to the
presence of the oxygen atom in the molecule, this class
of imines are very reactive toward the nucleophhiles used
J . Org. Chem, Vol. 68, No. 4, 2003 1203

Cimarelli et al.
1H NMR (300 MHz, CDCl3) δ 0.82 (t, 3 H, J ) 7.0 Hz), 1.00-
1.25 (m, 4 H), 1.30 (d, 3 H, J ) 6.6 Hz), 1.50-1.67 (m, 3 H),
3.31 (t, 1 H, J ) 7.0 Hz), 3.52 (q, 1 H, J ) 6.6 Hz), 7.20-7.40
(m, 10 H); 13C NMR (75 MHz, CDCl3) δ 14.0, 22.7, 25.2, 28.6,
38.5, 54.9, 60.0, 126.7, 127.0, 127.2, 127.8, 128.3, 128.4, 144.9,
145.9. Anal. Calcd for C19H25N, (267.409): C, 85.34; H, 9.42;
N, 5.24. Found: C, 85.27; H, 9.46; N, 5.01.
Da ta for (1S)-1-p h en yl-N-[(1′R)-1-p h en yleth yl]p en ta n -
1-a m in e [(1S,1′R)-6a b]: 1H NMR (300 MHz, CDCl3) δ 0.87
(t, 3 H, J ) 6.8 Hz), 1.00-1.32 (m, 4 H), 1.37 (d, 3 H, J ) 6.6
Hz), 1.54-1.90 (m, 3 H), 3.74 (t, 1 H, J ) 5.5 Hz), 3.75 (q, 1 H,
J ) 6.2 Hz), 7.20-7.60 (m, 10 H).
and do not need any Lewis acid or base activation. Good
to high diastereoselectivities were observed with aldi-
mines but more unusually with ketimines, and uncom-
mon diastereoisomers were prepared. This reaction al-
lows the preparation of aminophenols quaternary at the
C-1 carbon atom, which cannot be prepared with the
methods available till now. The sense of asymmetric
induction has been explained and confirmed in agreement
with the results previously obtained for hydride reduction
of the same substrates. The reaction allows the synthesis
of one or the other of the two diastereomers, choosing
the opportune starting imidoylphenol and the com-
mercially available organolithium reagent. Hypotheses
on transition-state models to explain the observed dia-
stereoselectivity were verified by molecular modeling
calculations.12 Further studies with other organometallic
reagents are in progress.
Da t a for (R,R)-2-p h en yl-N-(1-p h en ylet h yl)h exa n -2-
a m in e [(R,R)-6bb]: colorless oil; [R]20 +110.33 (c 1.15,
D
CHCl3); IR (neat) ν 3025, 2930, 1685, 1602, 1492, 1373, 1267,
762, 700 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.78 (t, 3 H, J )
7.0 Hz), 0.90-1.20 (m, 4H), 1.27 (d, 3 H, J ) 6.7 Hz), 1.37 (s,
3 H), 1.58-1.80 (m, 3 H), 3.60 (q, 1 H, J ) 6.7 Hz), 7.10-7.40
(m, 10 H); 13C NMR (75 MHz, CDCl3) δ 14.1, 23.1, 26.3, 27.0,
27.3, 41.3, 52.8, 59.5, 126.0, 126.2, 126.5, 126.6, 127.8, 128.1,
147.6, 148.5; API-ES MS m/z 282 (M+ + H). Anal. Calcd for
Exp er im en ta l Section
C
20H27N (281.485): C, 85.35; H, 9.67; N, 4.98. Found: C, 85.37;
H, 9.48; N, 7.87.
Gen er a l Meth od s. 1H and 13C NMR spectra were recorded
at 300 and 75 MHz, respectively, with CDCl3 as solvent at
ambient temperature and were calibrated using residual
undeuterated solvents as the internal reference. Coupling
constants are given in hertz. IR spectra were recorded using
an FTIR apparatus.
Ma ter ia ls a n d Solven ts. All reagents were commercially
available, were purchased at the highest quality, and were
purified by distillation when necessary. Hexane and toluene
were distilled and stored on sodium wire before use. The
following organolithium reagents were used: MeLi (1.6 M
solution in diethyl ether), BuLi (2.5 M solution in hexane),
PhLi (1.8 M solution in cyclohexane/diethyl ether, 70/30),
t-BuLi (1.7 M solution in pentane).
Da ta for (2S)-2-p h en yl-N-[(1R)-1-p h en yleth yl]h exa n -
2-a m in e [(1S,1′R)-6bb]: colorless oil; [R]20 +140.95 (c 2.0,
D
CHCl3); IR (neat) ν 3024, 2862, 1492, 1446, 1375, 1026, 762,
1
700 cm-1; H NMR (300 MHz, CDCl3) δ 0.82 (t, 3 H, J ) 7.0
Hz), 0.86-1.15 (m, 4H), 1.19 (s, 3 H), 1.20 (d, 3 H, J ) 6.6
Hz), 1.26 (m, 3 H), 3.57 (q, 1 H, J ) 6.7 Hz), 7.15-7.45 (m, 10
H); 13C NMR (75 MHz, CDCl3) δ 14.2, 23.3, 24.7, 26.4, 27.3,
45.7, 53.2, 59.9, 126.3, 126.4, 126.5, 126.6, 128.1, 128.3, 148.0,
149.6; API-ES MS m/z 282 (M+ + H). Anal. Calcd for C20H27
N
(281.485): C, 85.35; H, 9.67; N, 4.98. Found: C, 85.28; H, 9.50;
N, 5.13.
Data for 2-((1R)-1-{[(1′R)-1-ph en yleth yl]am in o}pen tyl)-
p h en ol [(R,R)-6cb]: colorless oil; IR (neat) ν 2964, 2935, 2859,
1469, 1261, 754 cm-1; 1H NMR (300 MHz, CDCl3) δ 0.82 (t, 3
H, J ) 7.0 Hz), 1.00-1.40 (m, 4 H), 1.44 (d, 3 H, J ) 6.6 Hz),
1.60-1.80 (m, 2 H), 2.00 (br s, 1 H), 3.43 (t, 1 H, J ) 7.0 Hz),
3.72 (q, 1 H, J ) 6.8 Hz), 6.72-6.96 (m, 3 H), 7.10-7.45 (m, 6
H), 13.78 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ 13.9, 22.4,
23.6, 28.3, 35.9, 55.2, 61.0, 116.6, 118.8, 125.5, 126.3, 127.4,
128.2, 128.7, 129.0, 143.5, 157.7. Anal. Calcd for C19H25NO
(283.408): C, 80.52; H, 8.89; N, 4.94. Found: C, 80.66; H, 8.81;
N, 4.81.
Dia ster eoselective Alk yla tion of 2-Im id oylp h en ols.
Syn th esis of Am in oa lk ylp h en ols (R)-6. Typ ica l P r oce-
d u r es. Meth od A. In the following typical procedure organo-
lithium reagent (7.0 mmol) was added dropwise to a stirred
solution of the imine (R)-5 (2.0 mmol) in dry hexane (10 mL)
at 0 °C under a nitrogen atmosphere over 15 min. After being
stirred for the time required for the complete conversion (1-4
1
h, following the progress of the reaction by TLC and H NMR),
allowing the temperature to rise slowly to ambient or higher
(40 °C for the preparation of 6d d ,ed ,fa ,fb,fd ), the reaction was
quenched with saturated ammonium chloride (20 mL). The
reaction mixture was diluted with CH2Cl2 (30 mL), and the
organic layer was separated, washed with brine, and dried over
Na2SO4. After removal of the solvent, the yellow oil obtained
was subjected to flash column chromatography on silica gel
with AcOEt/n-hexane (1/30 to 1/5, v/v) to give the pure
diastereomers.
Meth od B. Organolithium reagent (7.0 mmol) was added
dropwise to a stirred solution of the imine (R)-5 (2.0 mmol) in
dry toluene (10 mL) and TMEDA (7.0 mmol, 1.0 mL) at 0 °C
under a nitrogen atmosphere over 15 min. After the mixture
was stirred for the time required for the complete conversion
(15-60 min, following the progress of the reaction by TLC and
1H NMR), allowing the temperature to rise slowly to ambient,
the workup was carried out as described in method A.
The characterization of the prepared unknown aminophe-
nols 6a a -fd follows. Where the major diastereomer only was
obtained pure by chromatography, the 1H NMR signals for the
minor diastereomers were deduced from the spectra of the
crude reaction mixtures or from enriched chromatographic
fractions. When it was impossible to isolate the diastereomers
with high optical purity, the determination of optical activity
was omitted.
Da ta for 2-((1S)-1-{[(1′R)-1-ph en yleth yl]a m in o}p en tyl)-
p h en ol [(1S,1′R)-6cb]: colorless oil; [R]20 +71.2 (c 1.73,
D
CHCl3); IR (neat) ν 2958, 2930, 2859, 1491, 1474, 1256, 754,
1
699 cm-1; H NMR (300 MHz, CDCl3) δ 0.88 (t, 3 H, J ) 7.0
Hz), 1.00-1.40 (m, 4 H), 1.49 (d, 3 H, J ) 6.6 Hz), 1.60-1.80
(m, 2 H), 2.00 (br s, 1 H), 3.87 (q, 1 H, J ) 6.6 Hz), 3.90 (t, 1
H, J ) 7.1 Hz), 6.72-6.96 (m, 3 H), 7.10-7.45 (m, 6 H), 13.78
(br s, 1 H); 13C NMR (75 MHz, CDCl3) δ 14.0, 20.3, 22.6, 28.5,
35.1, 54.1, 61.0, 116.8, 118.7, 125.7, 126.5, 127.3, 128.3, 128.6,
128.8, 143.8, 157.4. Anal. Calcd for C19H25NO (283.408): C,
80.52; H, 8.89; N, 4.94. Found: C, 80.27; H, 8.71; N, 4.87.
Da t a for 2-((1S)-1-m et h yl-1-{[(1′R)-1-p h en ylet h yl]-
a m in o}p en tyl)p h en ol [(1S,1′R)-6d b]: yellow oil; [R]20D +6.72
(c 2.50, CHCl3); IR (neat) ν 2932, 1608, 1458, 1253 cm-1; H
1
NMR (300 MHz, CDCl3) δ 0.86 (t, 3 H, J ) 7.2 Hz), 1.05-1.25
(m, 4 H,), 1.33 (d, 3 H, J ) 6.7 Hz), 1.37 (s, 3 H), 1.55 (br s, 1
H), 1.80-2.10 (m, 2 H), 3.88 (q, 1 H, J ) 6.7 Hz), 6.70-7.60
(m, 9 H), 12.40 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ 14.6,
23.5, 25.4, 26.4, 26.7, 37.3, 53.5, 61.4, 117.7, 119.1, 126.4, 126.9,
127.5, 128.5, 128.6, 130.6, 146.2, 158.3. Anal. Calcd for C20H27
NO (297.435): C, 80.76; H, 9.15; N, 4.71. Found: C, 81.87; H,
9.02; N, 4.49.
Da ta for 2-((1R)-1-m eth yl-1-{[(1′R)-1-p h en yleth yl]-
a m in o}p en tyl)p h en ol [(R,R)-6d b]: 1H NMR (300 MHz,
CDCl3) δ 0.81 (t, 3 H, J ) 7.1 Hz), 1.05-1.25 (m, 4 H), 1.30 (d,
3 H, J ) 6.6 Hz), 1.47 (s, 3 H), 1.80-2.10 (m, 3 H), 4.00 (q, 1
H, J ) 6.7 Hz), 6.70-7.60 (m, 9 H), 12.40 (br s, 1 H).
-
Da ta for (1R)-1-p h en yl-N-[(1′R)-1-p h en yleth yl]p en ta n -
1-a m in e [(R,R)-6a b]: colorless oil; [R]20 +157.7 (c 1.28,
D
CHCl3); IR (neat) ν 2970, 2932, 2862, 1503, 1461, 1256 cm-1
;
1204 J . Org. Chem., Vol. 68, No. 4, 2003

Alkylation of Chiral 2-Imidoylphenols
Da ta for 2-((1S)-1-p h en yl-1-{[(1′R)-1-p h en yleth yl]-
am in o}eth yl)ph en ol [(1S,1′R)-6dc]: colorless oil; [R]20D +63.3
(c 2.89, CHCl3); IR (neat) ν 2981, 1583, 1453, 1258, 756, 702
128.5, 128.7, 158.0. Anal. Calcd for C21H29NO (311.461): C,
80.98; H, 9.38; N, 4.50. Found: C, 80.95; H, 9.42; N, 4.43.
Da t a for 2-((1S)-1-p h en yl-1-{[(1′R )-1-p h en ylet h yl]-
a m in o}p r op yl)p h en ol [(1S,1′R)-6ec]: yellow oil; IR (neat)
1
cm-1; H NMR (300 MHz, CDCl3) δ 1.26 (d, 3 H, J ) 6.6 Hz),
1
ν 2992, 1605, 1267, 763 cm-1; H NMR (300 MHz, CDCl3) δ
1.59 (s, 3 H), 2.83 (br s, 1 H), 3.64 (q, 1 H, J ) 6.7 Hz), 6.40-
7.70 (m, 14 H), 12.70 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ
24.5, 26.6, 53.6, 66.2, 117.1, 118.6, 126.3, 127.0, 127.4, 127.5,
128.4, 128.5, 128.6, 128.8, 132.1, 144.3, 146.7, 157.5; API-ES
MS m/z 318 (100, M+ + H). Anal. Calcd for C22H23NO
(317.424): C, 83.24; H, 7.30; N, 4.41. Found: C, 83.05; H, 7.47;
N, 4.32.
0.55 (t, 3 H, J ) 7.3 Hz), 1.14 (d, 3 H, J ) 6.6 Hz), 1.88-2.22
(m, 2 H), 2.64 (br s, 1 H), 3.58 (q, 1 H, J ) 6.8 Hz), 6.50-7.50
(m, 14 H), 12.65 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ 9.7,
26.3, 28.3, 53.1, 70.1, 117.3, 118.1, 126.4, 126.6, 127.2, 127.5,
128.2, 128.5, 128.9, 129.0, 130.5, 143.6, 146.5, 158.7. Anal.
Calcd for C23H25NO (331.451): C, 83.3; H, 7.60; N, 4.23.
Found: C, 83.50; H, 7.32; N, 4.15.
Da t a for 2-((1S)-1-p h en yl-1-{[(1′R )-1-p h en ylet h yl]-
a m in o}et h yl)p h en ol [(R,R)-6d c]: see the data for [(R,R)-
6fa ].
Da ta for 2-((1R)-1-p h en yl-1-{[(1′R)-1-p h en yleth yl]-
a m in o}p r op yl)p h en ol [(R,R)-6ec]: yellow oil; IR (neat) ν
2971, 2864, 1469, 1271 cm-1 1H NMR (300 MHz, CDCl3) δ
;
Data for 2-((1S)-1,2,2-tr im eth yl-1-{[(1′R)-1-ph en yleth yl]-
0.56 (t, 3 H, J ) 7.3 Hz), 1.40 (d, 3 H, J ) 7.0), 1.88-2.22 (m,
2 H), 2.64 (br s, 1 H), 3.84 (q, 1 H, J ) 6.6 Hz), 6.50-7.50 (m,
14 H), 12.65 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ 8.2, 24.7,
28.6, 53.1, 67.4, 117.5, 118.7, 126.7, 126.8, 128.1, 128.2, 128.3,
128.6, 129.4, 129.8, 130.8, 144.2, 146.0, 158.1. Anal. Calcd for
a m in o}p r op yl)p h en ol [(1S,1′R)-6d d ]: colorless oil; [R]20
D
-41.7 (c 0.64, CHCl3); IR (neat) ν 2982, 1603, 1452, 1261, 763,
1
751 cm-1; H NMR (300 MHz, CDCl3) δ 0.96 (s, 9 H), 1.33 (d,
3 H, J ) 7.0 Hz), 1.45 (s, 3 H), 2.32 (br d, 1 H, J ) 5.9 Hz),
4.02 (dq, 1 H, J ) 6.4, 6.2 Hz), 6.80-7.20 (m, 9 H), 13.60 (br
s, 1 H); 13C NMR (75 MHz, CDCl3) δ 21.9, 22.8, 26.2, 40.2,
54.0, 66.7, 117.1, 117.7, 126.2, 126.9, 127.3, 128.4, 128.9, 129.6,
146.7, 159.2. Anal. Calcd for C20H27NO (297.435): C, 80.76;
H, 9.15; N, 4.71. Found: C, 81.32; H, 8.98; N, 4.62.
C
23H25NO (331.451): C, 83.34; H, 7.60; N, 4.23. Found: C,
83.41; H, 7.39; N, 4.30.
Da ta for 2-((1S)-1-eth yl-2,2-d im eth yl-1-{[(1′R)-1-p h en -
ylet h yl]a m in o}p r op yl)p h en ol [(1S,1′R )-6ed ]: yellow oil;
[R]20D +37.3 (c 1.1, CHCl3); IR (neat) ν 2965, 1493, 1461, 1400,
Data for 2-((1R)-1,2,2-tr im eth yl-1-{[(1′R)-1-ph en yleth yl]-
am in o}pr opyl)ph en ol [(R,R)-6dd]: colorless oil; [R]20D +138.2
(c 0.73, CHCl3); IR (neat) ν 2963, 1606, 1461, 1295, 751, 699
cm-1; 1H NMR (300 MHz, CDCl3) δ 1.01 (s, 9 H), 1.52 (d, 3 H,
J ) 6.6 Hz), 1.72 (s, 3 H), 2.04 (br s, 1 H), 3.80-4.00 (m, 1 H),
6.50-7.20 (m, 9 H), 12.20 (br s, 1 H); 13C NMR (75 MHz,
CDCl3) δ 22.5, 26.5, 27.1, 40.2, 53.0, 67.0, 117.1, 117.4, 126.0,
126.3, 126.9, 128.2, 128.3, 129.8, 145.3, 158.3. Anal. Calcd for
1
1245, 756, 701 cm-1; H NMR (300 MHz, CDCl3) δ 0.63 (t, 3
H, J ) 7.1 Hz), 1.08 (s, 9 H), 1.60 (d, 3 H, J ) 6.6 Hz), 1.90-
2.30 (m, 2 H), 2.40 (br s, 1 H), 4.15-4.30 (m, 1 H), 6.60-7.40
(m, 9 H), 13.80 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ 9.5,
24.2, 26.7, 26.9, 28.2, 40.5, 52.8, 116.9, 117.8, 125.9, 126.5,
127.2, 128.2, 128.7, 131.1, 146.4, 159.3. Anal. Calcd for C21H29
-
NO (311.461): C, 80.98; H, 9.38; N, 4.50. Found: C, 80.73; H,
9.41; N, 4.62.
C
20H27NO (297.435): C, 80.76; H, 9.15; N, 4.71. Found: C,
Da ta for 2-((1R)-1-eth yl-2,2-d im eth yl-1-{[(1′R)-1-p h en -
81.45; H, 8.89; N, 4.84.
yleth yl]a m in o}p r op yl)p h en ol [(R,R)-6ed ]: yellow oil; [R]20
D
Da ta for 2-((1R)-1-m eth yl-1-{[(1′R)-1-p h en yleth yl]-
-100.8 (c 0.76, CHCl3); IR (neat) ν 2964, 1606, 1463, 757, 701
cm-1; 1H NMR (300 MHz, CDCl3) δ 0.95 (s, 9 H), 1.10 (t, 3 H,
J ) 7.3 Hz), 1.38 (d, 3 H, J ) 6.6 Hz), 2.05-2.35 (m, 2 H),
2.40 (br s, 1 H), 4.20 (q, 1 H, J ) 6.6 Hz), 6.80-7.40 (m, 9 H),
14.00 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ 11.5, 22.1, 25.5,
26.9, 41.3, 54.1, 70.0, 116.9, 117.3, 126.5, 127.5, 128.1, 128.9,
a m in o}p r op yl)p h en ol [(R,R)-6ea ]: yellow oil; [R]20 -15.4
D
(c 2.40, CHCl3); IR (neat) ν 2972, 1460, 1257, 754, 701 cm-1
;
1H NMR (300 MHz, CDCl3) δ 0.69 (t, 3 H, J ) 7.5 Hz), 1.29 (d,
3 H, J ) 7.0 Hz), 1.44 (s, 3 H), 1.52-1.70 (m, 1 H), 1.89-2.07
(m, 1 H), 2.00 (br s, 1 H), 4.00 (q, 1 H, J ) 6.7 Hz), 6.76-7.42
(m, 9 H), 12.75 (br s, 1 H); 13C NMR (75 MHz, CDCl3) δ 9.0,
23.4, 24.2, 34.5, 53.7, 61.8, 117.2, 118.7, 126.4, 127.2, 127.5,
128.7, 129.0, 129.2, 146.7, 158.1; API-ES MS m/z 270 (100,
M+ + H). Anal. Calcd for C18H23NO (269.381): C, 80.26; H,
8.61; N, 5.20. Found: C, 80.43; H, 8.52; N, 5.37.
130.6, 136.0, 145.8, 160.2. Anal. Calcd for
C21H29NO
(311.461): C, 80.98; H, 9.38; N, 4.50. Found: C, 80.80; H, 9.50;
N, 4.48.
Da ta for 2-((1R)-1-p h en yl-1-{[(1′R)-1-p h en yleth yl]-
a m in o}eth yl)p h en ol [(R,R)-6fa ]: yellow oil; IR (neat) ν
1
2975, 1600, 1448 cm-1; H NMR (300 MHz, CDCl3) δ 1.49 (d,
Da ta for 2-((1S)-1-m eth yl-1-{[(1′R)-1-p h en yleth yl]-
1
a m in o}p r op yl)p h en ol [(1S,1′R)-6ea ]: H NMR (300 MHz,
3 H, J ) 6.6 Hz), 1.87 (s, 3 H), 2.85 (br s, 1 H), 3.87 (q, 1 H, J
) 7.0 Hz), 6.80-7.40 (m, 14 H), 12.50 (br s, 1 H); 13C NMR
(75 MHz, CDCl3) δ 24.9, 26.1, 53.3, 64.9, 117.2, 118.6, 125.9,
126.3, 127.0, 127.1, 127.8, 128.1, 128.6, 128.8, 130.4, 145.2,
145.7, 157.9. Anal. Calcd for C22H23NO (317.424): C, 83.24;
H, 7.30; N, 4.41. Found: C, 83.32; H, 7.40; N, 4.39.
CDCl3) δ 0.83 (t, 3 H, J ) 7.6 Hz), 1.28 (d, 3 H, J ) 6.7 Hz),
1.37 (s, 3 H), 1.52-1.70 (m, 1 H), 1.89-2.07 (m, 1 H), 2.00 (br
s, 1 H), 3.92 (q, 1 H, J ) 6.7 Hz), 6.76-6.42 (m, 9 H), 12.75 (br
s, 1 H).
Data for 2-((1S)-1-eth yl-1-{[(1′R)-1-ph en yleth yl]am in o}-
p en tyl)p h en ol [(1S,1′R)-6eb]: colorless oil; [R]20 -11.0 (c
D
Da ta for 2-((1′R)-1-p h en yl-1-{[(1′R)-1-p h en yleth yl]-
a m in o}p en tyl)p h en ol [(R,R)-6fb]: colorless oil; IR (neat) ν
1.48, CHCl3); IR (neat) ν 2970, 1735, 1502, 1250 cm-1; 1H NMR
(300 MHz, CDCl3) δ 0.54 (t, 3 H, J ) 7.3 Hz), 0.88 (t, 3 H, J )
7.1 Hz), 0.92-1.15 (m, 4 H), 1.26 (d, 3 H, J ) 6.1 Hz), 1.48
(dq, 1 H, J ) 7.2, 13.6 Hz), 1.70-2.20 (m, 3 H), 2.10 (br s,
1H), 3.88 (q, 1 H, J ) 6.7 Hz), 6.68-7.60 (m, 9 H), 12.80 (br s,
1 H); 13C NMR (75 MHz, CDCl3) δ 8.4, 14.2, 23.0, 23.7, 24.8,
29.4, 30.9, 53.1, 63.9, 117.2, 118.3, 126.5, 127.1, 127.4, 128.3,
128.4, 128.7, 146.0, 158.1; API-ES MS m/z 312.0 (M+ + H, 100).
Anal. Calcd for C21H29NO (311.461): C, 80.98; H, 9.38; N, 4.50.
Found: C, 81.12; H, 9.50; N, 4.59.
2961, 2871, 1463, 1282 cm-1 1H NMR (300 MHz, CDCl3) δ
;
0.75 (t, 3 H, J ) 7.1 Hz), 0.90-1.10 (m, 6H), 1.43 (d, 3 H, J )
6.6 Hz), 1.50 (br s, 1 H), 3.84 (q, 1 H, J ) 6.7 Hz), 6.60-7.60
(m, 14 H), 11.75 (br s, 1 H). Anal. Calcd for C25H29NO
(359.504): C, 83.52; H, 8.13; N, 3.90. Found: C, 83.61; H, 8.09;
N, 4.18.
Da ta for 2-((1S)-1-p h en yl-1-{[(1′R)-1-p h en yleth yl]-
a m in o}p en tyl)p h en ol [(1S,1′R)-6fb]: 1H NMR (300 MHz,
CDCl3) δ 0.65 (t, 3 H, J ) 7.0 Hz), 0.90-1.01 (m, 6H), 1.15 (d,
3 H, J ) 7.0 Hz), 1.50 (br s, 1 H), 3.58 (q, 1 H, J ) 6.7 Hz),
6.60-7.60 (m, 14 H), 11.75 (br s, 1 H).
Da ta for 2-((1R)-2,2-d im eth yl-1-p h en yl-1-{[(1′R)-1-
p h en yleth yl]a m in o}p r op yl)p h en ol [(1S,1′R)-6fd ]: color-
less oil; IR (neat) ν 2984, 1616, 1473 cm-1; 1H NMR (300 MHz,
CDCl3) δ 1.23 (s, 9 H), 1.30 (d, 3 H, J ) 6.7 Hz), 1.55 (br s, 1
H), 4.48 (q, 1 H, J ) 6.4 Hz), 6.60-7.60 (m, 14 H), 12.30 (br s,
1 H); 13C NMR (75 MHz, CDCl3) δ 22.7, 28.8, 37.5, 54.6, 54.9,
Data for 2-((1R)-1-eth yl-1-{[(1′R)-1-ph en yleth yl]am in o}-
p en tyl)p h en ol [(R,R)-6eb]: colorless oil; IR (neat) ν 2960,
1
1730, 1493, 1254 cm-1; H NMR (300 MHz, CDCl3) δ 0.71 (t,
3 H, J ) 7.3 Hz), 0.79 (t, 3 H, J ) 7.3 Hz), 0.90-1.20 (m, 4 H),
1.25 (d, 3 H, J ) 6.4 Hz), 1.50 (br s, 1 H), 1.80-2.20 (m, 4 H),
3.89 (q, 1 H, J ) 6.6 Hz), 6.70-7.20 (m, 9 H), 12.60 (br s, 1 H);
13C NMR (75 MHz, CDCl3) δ 7.1, 13.9, 22.8, 23.6, 24.4, 25.8,
29.7, 35.7, 53.3, 117.3, 118.5, 126.6, 126.9, 127.6, 127.8, 128.1;
J . Org. Chem, Vol. 68, No. 4, 2003 1205

Cimarelli et al.
116.0, 117.4, 126.0, 126.6, 126.9, 127.0, 127.2, 128.3, 128.6,
128.7, 131.8, 132.4, 133.0, 160.7, 172.4. Anal. Calcd for C25H29
NO (359.504): C, 83.52; H, 8.13; N, 3.90. Found: C, 83.48; H,
8.24; N, 4.16.
nologica, Rome, and the University of Camerino (Na-
tional Project “Stereoselezione in Sintesi Organica.
Metodologie ed applicazioni”) is gratefully acknowl-
edged.
-
Da ta for 2-((1R)-2,2-d im eth yl-1-p h en yl-1-{[(1′R)-1-
p h en yleth yl]a m in o}p r op yl)p h en ol [(R,R)-6fd ]: colorless
oil; [R]20 -19.6 (c 0.8, CHCl3); IR (neat) ν 2964, 1606, 1452,
D
Su p p or tin g In for m a tion Ava ila ble: Computational re-
sults (Cartesian coordinates of the optimized geometries,
semiempirical PM3 level enthalpies of formation, and imagi-
nary frequencies) for Z-5a -Li, (R,R)-6d d , Re,Z-6a a -TS, Re,E-
6a a -TS, Si,E-6a a -TS, Re-6ca -TS, and Si-6ca -TS. This
material is available free of charge via the Internet at
http://pubs.acs.org.
756, 699 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.42 (s, 9 H), 1.55
(d, 3 H, J ) 6.6 Hz), 2.00 (br s, 1 H), 4.57 (q, 1 H, J ) 6.5 Hz),
6.60-7.60 (m, 14 H), 12.30 (br s, 1 H); 13C NMR (75 MHz,
CDCl3) δ 25.1, 31.3, 34.9, 60.2, 60.5, 117.3, 117.9, 120.0, 125.4,
126.3, 127.0, 127.1, 128.5, 130.8, 132.3, 132.4, 152.1, 163.4,
172.7. Anal. Calcd for C25H29NO (359.504): C, 83.52; H, 8.13;
N, 3.90. Found: C, 83.81; H, 7.98; N, 3.88.
Ack n ow led gm en t. Financial support from the Min-
istero dell’Universita` e della Ricerca Scientifica e Tec-
J O020423E
1206 J . Org. Chem., Vol. 68, No. 4, 2003