Enantioselective diethylzinc addition to aldehydes via chiral, non-racemic β-hydroxysalicylhydrazone catalysts

Article abstract of DOI:10.1016/j.tetasy.2008.02.007

A series of tridentate β-hydroxysalicylhydrazone ligands have been prepared from (1R,2S)-ephedrine and (1R,2S)-norephedrine and tested in the catalytic asymmetric addition of diethylzinc to aldehydes. The isolated chemical yields of the addition products

Full text of DOI:10.1016/j.tetasy.2008.02.007

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 607–611
Enantioselective diethylzinc addition to aldehydes via chiral,
non-racemic b-hydroxysalicylhydrazone catalysts
Raleigh W. Parrott II, Delvis D. Dore, Seshanand P. Chandrashekar, Jeromy T. Bentley,
Brittany S. Morgan and Shawn R. Hitchcock*
Department of Chemistry, Illinois State University, Normal, IL 61790-4160, United States
Received 2 January 2008; accepted 4 February 2008
Abstract—A series of tridentate b-hydroxysalicylhydrazone ligands have been prepared from (1R,2S)-ephedrine and (1R,2S)-norephe-
drine and tested in the catalytic asymmetric addition of diethylzinc to aldehydes. The isolated chemical yields of the addition products
ranged from 50% to 84%. The reactions exhibited very good enantioselectivity with enantiomeric ratios ranging from 89:11 to 96:4.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
H
Ph
The catalytic asymmetric addition of diorganozinc reagents
to carbonyl compounds is a well established reaction path-
way in synthetic organic chemistry.1 This process is driven
by the coordination of the diethylzinc species with an
appropriate ligand, often a chiral, non-racemic b-amino
alcohol.2 To this end, many different research groups have
sought to develop unique ligands that can serve as molec-
ular scaffolds for the transfer of asymmetry.1–4 Among
the ligands that have been synthesized and applied in dieth-
ylzinc addition reactions, salicylhydrazones represent a
class of compounds that have not been studied extensively.
The most notable literature examples have been developed
by Arai et al.3 The template developed by Arai et al. pos-
sess an axially chiral binaphthyl linker as the foundation
of the catalyst (Fig. 1). When employed in the asymmetric
addition of diethylzinc to benzaldehyde, this particular cat-
alyst afforded the addition product 1-phenyl-1-propanol
with an enantiomeric ratio of 79.0:21.0 favoring the
(S)-enantiomer. Arai et al. also prepared other catalyst
derivatives of a similar design and were able to obtain
enantiomeric ratios as high as 90.0:10.0.3 In a related body
of work, Hayashi et al. disclosed that b-hydroxysalicyli-
mines derived from tert-leucinol were effective catalysts
for the asymmetric addition of diethylzinc to aldehydes.5
We became interested in developing a structurally new
t-Bu
N
N
R
N
OH
HO
Arai and coworkers3
OH
Hayashi and coworkers5
R3
R2
OH HO
N
N
R1
R4
H
β-hydroxysalicylhydrazone
Fgure 1.
family of catalysts that combine the best elements of both
the Arai salicylhydrazone catalysts and the Hayashi
b-hydroxysalicylimines. The introduction of a chiral, non-
racemic b-amino alcohol foundation for the salicylhydraz-
one was considered to be a potential means of enhancing
the observed asymmetric induction. This presumption
was based on a variety of literature examples involving
b-hydroxysalicylimines (Schiff bases) as successful asym-
metric catalysts.5–7
Based on our work with the b-amino alcohols derived from
the Ephedra alkaloids,8 we sought to employ (1R,2S)-
ephedrine and (1R,2S)-norephedrine as chiral foundations.
*
Corresponding author. Tel.: +1 309 438 7854; fax: +1 309 438 5538;
e-mail: hitchcock@ilstu.edu
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.02.007

608
R. W. Parrott II et al. / Tetrahedron: Asymmetry 19 (2008) 607–611
Herein, we report the preparation of b-hydroxysalicylhyd-
razones and their application in the catalytic enantioselec-
tive addition of diethylzinc to aldehydes.
Ph
O
N
O
H
Zn
N
Et2Zn-Toluene
PhCHO
6h
H3C
CH3
Ph
H
7
2. Results and discussion
O
Et
The hydrazines of (1R,2S)-ephedrine and (1R,2S)-N-iso-
propyl-norephedrine were prepared as previously described
and then condensed with a variety of aromatic aldehydes to
produce hydrazone derivatives 6a–j (Table 1).8,9 In all
cases, the (E)-stereoisomer of the b-hydroxysalicylhydraz-
Ph
OH
(S)-configuration
H
H
Et Zn
CH3
N
Et
H
H
N
Zn
O
1
H3C
Ph
ones was the major isomer detected by H NMR spectro-
8
O
scopy. The stereochemical assignment was determined
based on the earlier work of Takahashi et al.10 The hydra-
zone ligands were subsequently applied in the asymmetric
1,2-addition of diethylzinc to benzaldehyde. It was deter-
mined that 3 equiv of diethylzinc at room temperature with
10 mol % loading of the catalyst resulted in the optimal
results for both yield and enantioselectivity (see Scheme 1).
Scheme 1. Proposed intermediate for catalyst 6h.
Table 2. Catalytic asymmetric additions of diethylzinc
OH
O
Et2Zn, toluene
When employed in the catalytic asymmetric addition of
diethylzinc to benzaldehyde, salicylhydrazone catalyst 6a
generated an enantiomeric ratio of 82.5:17.5 (S:R). In con-
trast, the benzylidene hydrazone catalyst 6b generated a
mixture of products that included the desired product (1-
phenyl-1-propanol), benzyl alcohol and the starting mate-
rial. The presence of the benzyl alcohol is indicative of
the failure of catalyst 6b, as benzyl alcohol is the direct
product of the reduction of benzaldehyde by diethylzinc.11
Ultimately, the results from entries 1 and 2 in Table 2
suggest that the presence of the phenolic unit is crucial
for stable catalytic activity and enantioselection. Salicyl-
hydrazone catalysts 6c–e (Table 2, entries 3–5) exhibited
Ph
Ph
H
Et
catalysts 6a-j
H
Entry
Catalysta
er (jR–Sj)b
Config.c
1
2
3
4
5
6
7
8
9
6a
6b
6c
6d
6e
6f
82.5:17.5 (65)
(S)
ndd
(R)
ndd
ndd
(S)
(S)
(S)
(S)
(S)
ndd
44.5:55.5 (11)
ndd
ndd
89:11 (78)
80.5:19.5 (61)
94:6 (88)
61:39 (22)
82.5:17.5 (65)
6g
6h
6i
10
6j
a All reactions went to completion as determined by 1H NMR spectro-
scopy and CSP HPLC.
b The enantiomeric ratio (er) values were determined via CSP HPLC using
a Chiralcel-OD column.
Table 1. b-Hydroxysalicylhydrazone synthesis
R2
c The configuration was determined by comparison with literature values
for retention times.12
(E)
OH
NH2
N
R2CHO, MgSO4
toluene, reflux
OH
N
N
H
d The er could not be determined due to the significant amount of benzyl
alcohol present.
Ph
R1
Ph
R1
CH3
CH3
poor reactivity and low enantioselectivity when compared
to the parent catalyst 6a. All these derivativesshare a com-
mon structural feature of substitution at the ortho-position
relative to the phenolic alcohol. The introduction of the
ortho-substituent caused the enantiomeric ratio to favor
the (R)-enantiomer in contrast to the principal formation
of the (S)-enantiomer in all other cases. Hayashi et al.5
observed a similar pattern of reactivity with their tridentate
b-hydroxysalicylimine derivatives. This suggested that the
region near the phenolic position must be free of steric
interference in order for the catalytic process to occur
efficiently.
4: R = CH3
5: R = CH(CH3)2
6a-j
28-80%
Entry Ligand R1
R2
Yield
(%)
1
2
3
4
5
6
7
8
9
10
6a
6b
6c
6d
6e
6f
–CH3 –2-Hydroxyphenyl
–CH3 –Phenyl
–CH3 –2-Hydroxy-3-methylphenyl
–CH3 –3-t-Butyl-2-hydroxyphenyl
–CH3 –3,5-Di-(t-butyl)-2-hydroxyphenyl 28a
–CH3 –2-Hydroxy-5-nitrophenyl
–CH3 –2-Hydroxy-5-methoxyphenyl
–CH3 –2-Hydroxy-1-naphthyl
–iPr
–iPr
43a
54b
51a
48b
43b
74a
46b
49a
80a
6g
6h
6i
–2-Hydroxyphenyl
–2-Hydroxy-1-naphthyl
Salicylhydrazone catalysts 6f and 6g were prepared to
examine the effects of different electronic substituents
(Table 2, entries 6 and 7). In contrast, the electronic effect
of the methoxy substituent was not significant in terms of
having an influence over the enantioselection. The intro-
6j
a Derivative was purified by flash chromatography (hexanes–ethyl acetate,
4:1).
b Derivative was purified by recrystallization (ether–hexanes, 1:2).

R. W. Parrott II et al. / Tetrahedron: Asymmetry 19 (2008) 607–611
609
duction of a nitro group onto the aromatic ring at the para-
3. Conclusion
position of the salicylhydrazone (entry 7) improved the
enantioselection of the catalysis process to a ratio of
89.0:11.0. It is proposed that the origin of the increase
might be related to the pKa difference between p-nitro-
phenol and phenol (i.e., 7.2 vs 9.9), as well as the different
binding abilities of the phenoxide system versus a p-nitro-
phenoxide system.13
There are mechanistic factors that are involved but are not
clear at this time. These include the impact of ortho-substit-
uents on the phenolic ring, the impact of electronic tuning
of the phenolic ring, and the difference in enantioselectivity
based on the Ephedra nitrogen substituent (methyl vs iso-
propyl). Studies are currently underway to address these
aspects in the context of the catalytic ability of the b-
hydroxysalicylhydrazones.
To expand on the variety of the salicylaldehyde derivatives,
2-hydroxy-1-naphthaldehyde was employed as the aro-
matic base of salicylhydrazone catalyst 6h. This derivative
afforded the highest enantioselection for catalysis of the
asymmetric addition of diethylzinc to benzaldehyde with
a ratio of 94:6. The presence of the extended aromatic ring
system apparently provides an environment, that is, condu-
cive to catalysts.
4. Experimental
4.1. General
All reactions were run under a nitrogen atmosphere. Anhy-
drous toluene was purchased and stored under a nitrogen
atmosphere. Diethylzinc was purchased as a 1 M solution
In an effort to further enhance the stereoselectivity of the
catalytic process, the N-isopropylnorephedrine catalysts
were employed. It was anticipated that the N-isopropyl
group of the norephedrine derivative would be more effec-
tive than the N-methyl group of ephedrine. However, the
result of applying the norephedrine based catalysts 6i and
6j indicated otherwise. The salicylaldehyde derived 6i
yielded an enantiomeric ratio of 61:39. This was a signifi-
cant decrease in enantioselection when compared to the
case of the salicylaldehyde derived 6a. The decrease in
enantioselectivity was also observed with catalyst 6j. These
collected results suggested that the presence of a larger sub-
stituent on the nitrogen has a negative impact on the ste-
reochemical outcome of the catalyst, perhaps through a
conformational change in the catalyst structure.
1
in hexanes. Unless otherwise noted, all H and 13C NMR
spectra were recorded at 25 °C in CDCl3 operating at
400 MHz and 100 MHz, respectively. Chemical shifts are
reported in parts per million (d scale), and coupling con-
stants (J values) are listed in Hertz (Hz). Infrared spectra
are reported in reciprocal centimeters (cmꢀ1) and are mea-
sured either as a neat liquid or as a KBr window. Melting
points were recorded on a Mel-Temp apparatus and are
uncorrected. Mass spectral analyses were conducted by
the mass spectrometry analytical laboratories of the Uni-
versity of Illinois at Urbana-Champaign using a quadra-
pole time of flight mass spectrometer hybrid with MS/
MS capability. Optical activities were measured at
589 nm using a Jasco digital polarimeter purchased with
NSF Grant #CHE 644950.
Ultimately, catalyst 6h, a (1R,2S)-ephedrine based salicyl-
hydrazone with the naphthyl unit as the aromatic founda-
tion, proved to be the most effective catalyst in the family
of b-hydroxysalicylhydrazones and was tested with a series
of aldehydes (Table 3). The isolated yield of the addition
products ranged from 50% to 84% after chromatography,
while the enantiomeric ratios ranged from 89:11 to 96:4.
With regard to the mechanism of this catalytic process, it
is proposed that catalyst 6h undergoes a reaction with a
single equivalent of diethylzinc to form a tridentate cata-
lyst, similar to the Hayashi catalyst.5
4.2. General procedure for the synthesis of
b-hydroxysalicylhydrazones
Either the b-hydroxyhydrazine derived from (1R,2S)-
ephedrine 4 or b-hydroxyhydrazine 5 derived from
(1R,2S)-N-isopropyl-norephedrine (1.62 g, 8.98 mmol)
was dissolved in toluene (10 mL) in a flame dried flask un-
der an inert atmosphere. The aldehyde (8.98 mmol) of
choice was added and allowed to stir for 22 h at reflux.
Toluene was removed under reduced pressure and the
hydrazone was extracted with ethyl acetate (50 mL ꢁ 2),
washed with brine, dried with magnesium chloride, gravity
filtered, and concentrated under reduced pressure. The
hydrazones were either recrystallized in ether and hexanes
(1:2) or purified via flash chromatography.
Table 3. Catalytic asymmetric additions of Et2Zn with b-hydroxy-
salicylhydrazone 6h
O
6h, Et2Zn
H
OH
Et
toluene, 18 h, 25 o
C
R
R
H
4.2.1. 2-[(E)-(2-((1R,2S)-1-Hydroxy-1-phenyl-2-propyl)-2-
methylhydrazono)methyl]phenol 6a. (1R,2S)-Ephedrine 4
and 2-hydroxybenzaldehyde were reacted to yield com-
pound 6a as a yellow oil after chromatography (43%).
½aꢂD ¼ þ233:6 (c 0.62, CHCl3). H NMR (CDCl3): d 1.33
(d, J = 6.6 Hz, 3H), 2.13 (br s, 1H), 2.72 (s, 3H), 3.55 (pen-
tet, J = 6.6 Hz, 1H), 4.87 (d, J = 5.1 Hz, 1H), 6.82–6.93 (m,
2H), 7.07–7.32 (m, 7H), 11.54 (br s, 1H). 13C NMR
(CDCl3): d 12.9, 35.8, 67.7, 76.2, 116.1, 119.0, 120.1,
126.1, 127.5, 128.0, 128.2, 128.4, 133.9, 142.4, 156.2. IR
Entry
R
Yield (%)
(jR–Sj)a
Config.b
1
2
3
4
5
–C6H5
–C6H4Cl
–1-C10H7
–1-C10H7
74
50
84
63
67
94:6 (88)
96:4 (92)
92:8 (84)
95:4 (91)
89:11 (78)
(S)
(S)
(S)
(S)
(S)
25
1
–t-CH@CHPh
a The enantiomeric ratio (er) values were determined via CSP HPLC using
a Chiralcel-OD column.
b The configuration was determined by comparison of literature values for
optical activity.12

610
R. W. Parrott II et al. / Tetrahedron: Asymmetry 19 (2008) 607–611
(neat): 3438, 1034, 911, 752, 702 cmꢀ1. ESI-HRMS calcd
for C17H21N2O2 (M+H+): 285.1603. Found: 285.1602.
4.2.6. 2-((E)-(2-((1R,2S)-1-Hydroxy-1-phenyl-2-propyl)-
2-methylhydrazono)methyl)-4-nitrophenol 6f. (1R,2S)-
Ephedrine 4 and 2-hydroxy-5-nitrobenzaldehyde were
combined and the title compound was obtained as an
4.2.2. (1R,2S)-2-[(E)-2-Benzylidene-1-methylhydrazinyl]-1-
phenylpropan-1-ol 6b. (1R,2S)-Ephedrine 4 and benzalde-
hyde were combined to yield compound 6b as a white solid
orange solid after recrystallization (43%). Mp = 147–
25
149 °C. ½aꢂD ¼ þ180:4 (c 0.60, CHCl3). 1H NMR (CDCl3):
25
1
d 1.39 (d, J = 7.0 Hz, 3H), 1.98 (br s, 1H), 2.79 (s, 3H), 3.66
(pentet, J = 6.3 Hz, 1H), 4.87 (d, J = 5.9 Hz, 1H), 6.95 (d,
J = 8.0 Hz, 1H), 7.16 (s, 1H), 7.26–7.34 (m, 4H), 8.00–8.02
(m, 2H), 12.37 (s, 1H). 13C NMR (CDCl3): d 13.3, 36.0,
68.0, 76.7, 116.6, 120.3, 123.7, 124.0, 126.1, 128.0, 128.5,
130.4, 140.3, 142.0, 162.0. IR (CHCl3): 3530, 1092, 900,
(54%). Mp = 51–53 °C. ½aꢂD ¼ þ140:2 (c 0.71, CHCl3). H
NMR (CDCl3): d 1.05 (d, J = 6.6 Hz, 3H), 2.93 (s, 3H),
3.39 (qd, J = 2.0 Hz, J = 6.6 Hz, 1H), 5.01 (s, 1H), 5.34
(br s, 1H), 7.23–7.28 (m, 3H), 7.33–7.37 (m, 3H), 7.42–
7.44 (m, 2H), 7.52–7.54 (m, 2H). 13C NMR (CDCl3): d
9.1, 37.3, 67.0, 76.4, 125.1, 125.7, 126.6, 127.2, 127.7,
128.3, 132.4, 135.9, 141.7. IR (CHCl3): 3398, 1051, 912,
751, 702 cmꢀ1
(M+H+): 330.1454. Found: 330.1463.
.
ESI-HRMS calcd for C17H20N3O4
754, 700 cmꢀ1
.
ESI-HRMS calcd for C17H21N2O
(M + H+): 269.1654. Found: 269.1653.
4.2.7.
2-((E)-(2-((1R,2S)-1-Hydroxy-1-phenyl-2-propyl)-
2-methylhydrazono)methyl)-4-methoxyphenol 6g. (1R,2S)-
Ephedrine 4 and 2-hydroxy-5-methoxybenzaldehyde were
4.2.3. 2-[(E)-(2-((1R,2S)-1-Hydroxy-1-phenyl-2-propyl)-2-
methylhydrazono)methyl]-6-methylphenol
6c. (1R,2S)-
reacted to yield the title compound as a clear oil after chro-
Ephedrine 4 and 2-hydroxy-3-methylbenzaldehyde were
combined to yield compound 6c as a clear oil after chroma-
25
matography (74%). ½aꢂD ¼ þ175:8 (c 0.59, CHCl3). 1H
25
1
NMR (CDCl3): d 1.34 (d, J = 6.6 Hz, 3H), 2.08 (br s,
1H), 2.73 (s, 3H), 3.57 (pentet, J = 6.6 Hz, 1H), 3.76 (s,
3H), 4.88 (dd, J = 2.4, 5.1 Hz, 1H), 6.64 (d, J = 2.4 Hz,
1H), 6.71–6.73 (m, 1H), 6.84–6.86 (m, 1H), 7.15 (s, 1H),
7.26–7.33 (m, 4H), 11.08 (s, 1H). 13C NMR (CDCl3): d
13.0, 36.0, 55.7, 67.8, 76.3, 113.2, 114.0, 116.6, 120.3,
126.2, 127.6, 128.3, 133.4, 142.5, 150.4, 152.3. IR (neat):
3454, 1039, 910, 762, 702 cmꢀ1. ESI-HRMS calcd for
C18H23N2O3 (M+H+): 315.1709. Found: 315.1708.
tography (51%). ½aꢂD ¼ þ219:7 (c 0.72, CHCl3). H NMR
(CDCl3): d 1.36 (d, J = 7.0 Hz, 3H), 2.02 (d, J = 3.1 Hz,
1H), 2.30 (s, 1H), 2.71 (s, 3H), 3.55 (pentet, J = 6.6 Hz,
1H), 4.92 (dd, J = 3.1, 6.2 Hz, 1H), 6.75–6.79 (m, 1H),
6.94–7.03 (m, 2H), 7.23–7.36 (m, 5H), 11.71 (s, 1H). 13C
NMR (CDCl3): d 13.0, 15.7, 36.2, 67.8, 76.3, 118.6,
119.4, 125.0, 126.2, 126.4, 127.6, 128.3, 129.5, 134.6,
142.5, 154.6. IR (neat): 3426, 1564, 1036, 913, 744,
702 cmꢀ1. ESI-HRMS calcd for C18H23N2O2 (M+H+):
299.1760. Found: 299.1758.
4.2.8. 1-((E)-(2-((1R,2S)-1-Hydroxy-1-phenyl-2-propyl)-2-
methylhydrazono)methyl)naphthalen-2-ol
6h. (1R,2S)-
4.2.4. 2-tert-Butyl-6-((E)-(2-((1R,2S)-1-hydroxy-1-phenyl-2-
6d. (1R,2S)-
Ephedrine and 2-hydroxy-1-naphthaldehyde were
4
propyl)-2-methylhydrazono)methyl)phenol
Ephedrine 4 and 2-hydroxy-3-tert-butylbenzaldehyde were
combined to yield the title compound, which was obtained
as a dark yellow solid after recrystallization (46%).
combined to yield compound 6d as a yellow solid after
25
Mp = 123–125 °C. ½aꢂD ¼ þ192:8 (c 0.63, CHCl3). 1H
25
recrystallization (48%). Mp = 100–101 °C. ½aꢂD ¼ þ191:9
(c 0.62, CHCl3). 1H NMR (CDCl3):
d 1.36 (d,
NMR (CDCl3): d 1.40 (d, J = 6.6 Hz, 3H), 2.02 (br s,
1H), 2.87 (s, 3H), 3.65 (septet, J = 6.6 Hz, 1H), 4.97 (d,
J = 4.3 Hz, 1H), 7.19–7.38 (m, 6H), 7.44–7.48 (m, 1H),
7.67 (d, J = 9.0 Hz, 1H), 7.77 (d, J = 7.8 Hz, 1H), 7.99
(d, J = 8.6 Hz, 1H), 8.05 (s, 1H), 12.69 (s, 1H). 13C
NMR (CDCl3): d 12.9, 36.0, 67.9, 76.2, 110.4, 118.9,
120.1, 122.7, 126.1, 126.4, 127.6, 128.2, 128.8, 129.2,
130.6, 131.1, 142.4, 155.5. IR (CHCl3): 3438, 1622, 1047,
952, 745, 702 cmꢀ1. ESI-HRMS calcd for C21H23N2O2
(M+H+): 335.1760. Found: 335.1758. Anal. Calcd for
C21H23N2O2: C, 75.42; H, 6.63; N, 8.38. Found: C, 75.10;
H, 6.58; N, 8.33.
J = 6.6 Hz, 3H), 1.46 (s, 9H), 2.01 (br s, 1H), 2.74 (s,
3H), 3.60 (m, 1H), 4.92 (dd, J = 3.1, 5.6 Hz, 1H), 6.77–
6.80 (m, 1H), 6.96–6.98 (m, 1H), 7.16–7.18 (m, 1H),
7.26–7.37 (m, 5H), 11.90 (s, 1H). 13C NMR (CDCl3): d
13.0, 29.4, 34.8, 35.9, 67.7, 76.2, 118.2, 120.0, 125.7,
126.3, 127.2, 127.7, 128.3, 135.7, 136.6, 142.4, 155.8. IR
(CHCl3): 3414, 1566, 1038, 910, 748, 702 cmꢀ1. ESI-HRMS
calcd for C21H29N2O2 (M+H+): 341.2229. Found:
341.2232.
4.2.5.
2,4-Di-tert-butyl-6-((E)-(2-((1R,2S)-1-hydroxy-1-
phenyl-2-propyl)-2-methylhydrazono)methyl)phenol 6e. (1R,
2S)-Ephedrine 4 and 3,5-di-tert-butyl-2-hydroxy benzalde-
4.2.9. 2-((E)-(2-((1R,2S)-1-Hydroxy-1-phenyl-2-propyl)-2-
isopropylhydrazono)methyl)phenol 6i. (1R,2S)-Norephe-
drine based hydrazine 5 and 2-hydroxybenzaldehyde were
hyde were combined and the title compound was obtained
25
as a clear oil after chromatography (28%). ½aꢂD ¼ þ111:3 (c
1
0.80, CHCl3). H NMR (CDCl3): d 1.30 (s, 9H), 1.34 (d,
reacted to form the title compound, which was obtained
25
J = 6.6 Hz, 3H), 1.47 (s, 9H), 2.02 (br s, 1H), 2.73 (s,
3H), 3.57 (pentet, J = 6.3 Hz, 1H), 4.92 (dd, J = 3.5,
6.3 Hz, 1H), 6.96–6.97 (m, 1H), 7.22–7.37 (m, 6H), 11.72
(s, 1H). 13C NMR (CDCl3): d 12.9, 29.5, 31.6, 34.1, 35.0,
36.1, 67.8, 76.2, 77.2, 119.1, 123.2, 123.8, 126.3, 127.6,
128.3, 135.9, 136.5, 140.3, 142.6, 153.5. IR (neat): 3419,
909, 738, 701 cmꢀ1. ESI-HRMS calcd for C25H37N2O2
(M+H+): 397.2855. Found: 397.2864.
as a yellow oil after chromatography (49%). ½aꢂD ¼
þ314:4 (c 0.70, CHCl3). 1H NMR (CDCl3): d 0.79 (d,
J = 6.6 Hz, 3H), 1.09 (d, J = 6.6 Hz, 3H), 1.35 (d,
J = 6.6 Hz, 3H), 2.28 (br s, 1H), 3.68 (sextet, J = 6.6 Hz,
1H), 3.82 (septet, J = 6.6 Hz, 1H), 4.88 (d, J = 6.6 Hz,
1H), 6.83–6.94 (m, 2H), 7.07–7.14 (m, 2H), 7.22–7.39 (m,
5H), 11.81 (s, 1H). 13C NMR (CDCl3): d 14.9, 18.5, 19.6,
47.6, 58.3, 76.6, 116.1, 119.0, 120.5, 126.3, 127.6, 127.8,

R. W. Parrott II et al. / Tetrahedron: Asymmetry 19 (2008) 607–611
611
128.1, 128.2, 132.5, 142.8, 156.4. IR (neat): 3428, 1591,
Arts and Sciences. The authors acknowledge partial sup-
port for this work by the National Science Foundation
(NSF CHE #644950) and the donors of the Petroleum Re-
search Fund as administered by the American Chemical
Society (PRF B #40777–1). The authors also acknowledge
the support from Ms. Brittany Morgan by the American
Chemical Society in the form of summer support for partic-
ipation in project SEED.
1033, 910, 751, 701 cmꢀ1
.
ESI-HRMS calcd for
C19H25N2O2 (M+H+): 313.1916. Found: 313.1918.
4.2.10. 1-((E)-(2-((1R,2S)-1-Hydroxy-1-phenyl-2-propyl)-2-
isopropylhydrazono)methyl)naphthalen-2-ol 6j. (1R,2S)-
Norephedrine based hydrazine 5 and 2-hydroxy-1-naph-
thaldehyde were reacted to yield the title compound, which
was obtained as a yellow oil after chromatography (80%).
There was an impurity (ca. 5%) that could not be efficiently
References
25
removed ½aꢂD ¼ þ196:6 (c 0.63, CHCl3). 1H NMR (CDCl3):
d 0.92 (d, J = 6.6 Hz, 3H), 1.18 (d, J = 6.6 Hz, 3H), 1.41 (d,
J = 6.6 Hz, 3H), 1.55 (br s, 1H), 2.20 (br s, 1H), 3.77 (m,
1H), 3.96 (m, 1H), 4.97 (d, J = 6.6 Hz, 1H), 7.20–7.48 (m,
7H), 7.67 (d, J = 8.6 Hz, 1H), 7.77 (d, J = 8.2 Hz, 1H),
7.99 (d, J = 8.6 Hz, 1H), 8.32 (s, 1H), 12.99 (s, 1H). 13C
NMR (CDCl3): d 14.5, 18.5, 19.6, 48.2, 58.7, 76.3, 110.5,
118.9, 120.0, 122.7, 126.2, 126.3, 127.5, 128.1, 128.2,
128.9, 129.1, 130.5, 131.1, 142.8, 155.9. IR (neat): 3434,
1622, 1042, 909, 734, 701 cmꢀ1. ESI-HRMS calcd for
C23H27N2O2 (M+H+): 363.2073. Found: 363.2064.
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This research was funded in part by a Research Enhance-
ment Award from Illinois State University’s College of