Synthesis of chiral sulfamide-amine alcohol ligands for enantioselective alkylation of aldehydes

Article abstract of DOI:10.1080/00397910902806265

A series of chiral sulfamide-amine alcohols (SAA) (1-6) has been easily synthesized from commercially available chiral amino alcohols. In the absence of Ti(OiPr)4, ligand 4 catalyzed the asymmetric addition of diethylzinc to aromatic aldehydes with moderate to good yields and enantioselectivities.

Full text of DOI:10.1080/00397910902806265

This article was downloaded by: [University of Illinois Chicago]
On: 18 May 2012, At: 08:29
Publisher: Taylor & Francis
Informa Ltd Registered in England and Wales Registered Number: 1072954
Registered office: Mortimer House, 37-41 Mortimer Street, London W1T 3JH,
UK
Synthetic Communications: An
International Journal for Rapid
Communication of Synthetic
Organic Chemistry
Publication details, including instructions for
authors and subscription information:
http://www.tandfonline.com/loi/lsyc20
Synthesis of Chiral
Sulfamide–Amine Alcohol
Ligands for Enantioselective
Alkylation of Aldehydes
Jincheng Mao a
a Key Laboratory of Organic Synthesis of Jiangsu
Province, College of Chemistry, Chemical
Engineering and Materials Science, Suzhou
University, Suzhou, China
Available online: 08 Sep 2009
To cite this article: Jincheng Mao (2009): Synthesis of Chiral Sulfamide–Amine Alcohol
Ligands for Enantioselective Alkylation of Aldehydes, Synthetic Communications: An
International Journal for Rapid Communication of Synthetic Organic Chemistry, 39:20,
3710-3721
To link to this article: http://dx.doi.org/10.1080/00397910902806265
PLEASE SCROLL DOWN FOR ARTICLE
Full terms and conditions of use: http://www.tandfonline.com/page/terms-
and-conditions
This article may be used for research, teaching, and private study purposes.
Any substantial or systematic reproduction, redistribution, reselling, loan,

sub-licensing, systematic supply, or distribution in any form to anyone is
expressly forbidden.
The publisher does not give any warranty express or implied or make any
representation that the contents will be complete or accurate or up to
date. The accuracy of any instructions, formulae, and drug doses should be
independently verified with primary sources. The publisher shall not be liable
for any loss, actions, claims, proceedings, demand, or costs or damages
whatsoever or howsoever caused arising directly or indirectly in connection
with or arising out of the use of this material.

Synthetic Communications1, 39: 3710–3721, 2009
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397910902806265
Synthesis of Chiral Sulfamide–Amine
Alcohol Ligands for Enantioselective
Alkylation of Aldehydes
Jincheng Mao
Key Laboratory of Organic Synthesis of Jiangsu Province, College
of Chemistry, Chemical Engineering and Materials Science,
Suzhou University, Suzhou, China
Abstract: A series of chiral sulfamide–amine alcohols (SAA) (1–6) has been easily
synthesized from commercially available chiral amino alcohols. In the absence of
Ti(OiPr)4, ligand 4 catalyzed the asymmetric addition of diethylzinc to aromatic
aldehydes with moderate to good yields and enantioselectivities.
Keywords: Amine alcohols, asymmetric addition, diethylzinc, enantioselectivities
INTRODUCTION
Optically active secondary alcohols are important building blocks for the
synthesis of many optically and biologically active compounds.[1]
The enantioselective addition of organozinc reagents to carbonyl
compounds represents one of the most useful ways, because of its simul-
taneous formation of a new C-C bond and a stereogenic center in one
step. Thus, the development of various chiral ligands as catalysts for
the enantioselective alkylation has gained considerable significance over
the past two decades.[2–5] For these reactions to be successfully exploited
in large-scale applications, the chiral ligands shoud be readily available or
Received June 27, 2008.
Address correspondence to Jincheng Mao, Key Laboratory of Organic
Synthesis of Jiangsu Province, College of Chemistry, Chemical Engineering and
Materials Science, Suzhou University, Suzhou 215 123, China. E-mail: jcmao@
suda.edu.cn
3710

SAA Ligands for Asymmetric Alkylation
3711
Figure 1. Evaluated ligands in the study.
easily recycled. However, from the relevant reviews,[3] it can be seen that
only a small number of effective ligands were obtained by simple
synthetic methods. As to the catalytic reaction, an additional Lewis acid
such as Ti(OiPr)4 is always required for high efficiency. There is no doubt
that the addition of the moisture-sensitive Ti(OiPr)4 will increase the cost
and operational difficulty of the catalytic reaction. Therefore, stable,
easily accessible, and operationally simple ligands are still desirable for
the enantioselective alkylation without using Ti(OiPr)4. From the pub-
lished papers, it can be seen that Ti(OiPr)4 is necessary for the asymmetric
catalytic reaction promoted by chiral sulfonamide ligands.[6–9] In con-
trast, we have conveniently prepared a novel type of chiral sulfamide–
amine alcohols (SAA) for highly enantioselective addition of diethylzinc
to both aromatic and aliphatic or a,b-unsaturated aldehydes without
using Ti(OiPr)4.[10,11] As part of further extending the application of
our methodology, in this article, we report our finding of another series
of chiral SAA (1–6) (Fig. 1) for the asymmetric addition of diethylzinc
to aldehydes in the absence of Ti(OiPr)4.
RESULTS AND DISCUSSION
SAA ligands were easily prepared from the corresponding chiral aziridine
(7) and chiral amino alcohols (8 and 9) in one step in an atom-economical
synthesis (Scheme 1). Notably, 7 was also conveniently synthesized from
commercially available chiral phenylglycinol.[12] As shown, the desired
chiral compounds were obtained by simple flash-column chromatogra-
phy in moderate yields (38–47%). Meanwhile, these ligands are stable

3712
J. Mao
Scheme 1. Synthesis of the novel SAA ligands.
for several months in air. Given our interest in stereoselective
reactions,[13] we decided to investigate the catalytic property of these
chiral compounds as ligands in asymmetric catalysis. The asymmetric
addition of diethylzinc to benzaldehyde, which has been considered a
typical catalytic asymmetric benchmark reaction, was chosen as the
model reaction. The relevant results are listed in Table 1. It can be seen
that ligand 4 induced the catalytic reaction with best enantioselectivity
Table 1. Asymmetric addition of diethylzinc to benzaldehyde using SAA ligands
1–6a
Entry
Ligand
Solvent
Time (h)
Ee (%)b
Config.c
1
2
3
4
5
6
7
1
2
3
4
5
6
6
Toluene
Toluene
Toluene
Toluene
Toluene
Toluene
Hexane
24
24
24
24
24
24
24
15
34
52
62
28
46
30
R
S
R
S
R
S
S
aEt2Zn=aldehyde=ligand ¼ 2.2:1:0.1; 24 h. In all cases, the isolated yield of the
corresponding chiral secondary alcohol was 90–99%.
bThe ee values were determined by GC.
cThe absolute configuration assigned by comparison to literature values.

SAA Ligands for Asymmetric Alkylation
3713
(62% ee) (Table 1, entry 4). Notably, chiral ligands (1–6) with different
matching of stereogenic configurations gave the corresponding chiral
products with different configurations. It can be concluded that this dif-
ference is possibly attributed to the configuration of the chiral aziridine
used. By scanning the published papers, we can see that either toluene
or hexane is considered the best solvent for asymmetric addition of
diethylzinc to aldehydes. However, hexane was not a suitable solvent
for our catalytic system (entry 7).
It is well known that the additives have an important role in the
catalytic reactions.[14] Thus, various additives were employed, such as
DMAP (4-dimethylaminopyridine), imidazole, TMSCl (trimethyl chloro-
silane), Et3N, and DiMPEG (dimethoxy polyethylene glycol,
Mn ¼ 2000).[15] Generally, dissapointing results were obtained (Table 2,
entries 2–6).
With the optimal condition in hand, various aromatic aldehydes were
used as the substrates in the catalytic reaction. The relevant results are
listed in Table 3. It can be seen that donor group in the para-position
of the aromatic ring was unfavorable for the enantioselectivity (Table 3,
entry 6). Generally, the chiral ligand 4 showed good chemical selectivities
and moderate enantioselectivities in the asymmetric ethylation of
aromatic aldehydes. The good enantioselectivity was obtained when
2-fluorobenzaldehyde was investigated as the substrate (entry 2). When
the asymmetric addition of diethylzinc to 2-naphthaldehyde was per-
formed at 0ꢀC, the corresponding chiral product was obtained with
70% ee (entry 11).
Table 2. Additive-mediated asymmetric addition of diethyl-
zinc to benzaldehyde induced by 4a
Entry
Ligand
Additive
Ee (%)b
Config.c
1
2
3
4
5
6
4
4
4
4
4
4
—
62
6
40
1
2
52
S
S
S
—
—
S
DMAP
Imidazole
TMSCl
Et3N
DIMPEG
aEt2Zn=aldehyde=ligand ¼ 2.2:1:0.1; 24 h. In all cases, the
isolated yield of the corresponding chiral secondary alcohol
was 90–99%.
bThe ee values were determined by GC.
cThe absolute configuration assigned by comparison to
literature values.

3714
J. Mao
Table 3. Asymmetric addition of diethylzinc to various aromatic aldehydes
induced by 4a
Yield
(%)b
Ee
(%)c
Entry
Substrates
Benzaldehyde
2-Fluorobenzaldehyde
2-Chlorobenzaldehyde
3-Chlorobenzaldehyde
4-Chlorobenzaldehyde
4-Bromobenzadehyde
4-Tolualdehyde
Config.d
1
2
3
4
5
6
7
8
9
99
98
85
71
91
82
67
95
74
97
83
62
66
63
46
50
52
48
62
33
50
70
S
S
S
S
S
S
S
S
S
S
S
4-(Trifluoromethyl)benzaldehyde
1-Naphthaldehyde
2-Naphthaldehyde
10
11e
2-Naphthaldehyde
aEt2Zn=aldehyde=ligand ¼ 2.2:1:0.1; hexane, rt, 24 h.
bIsolated yield.
cThe ee values were determined by GC.
dThe absolute configuration assigned by comparison with literature values.
e
ꢀ
The catalytic reaction was performed at 0 C.
To prove the efficiency of our catalytic system, it was applied to a
copper-catalyzed asymmetric Henry reaction. To our astonishment, we
got only the racemic product when the SAA ligand 4 was used
(Scheme 2). However, under the nonoptimized conditions, the corre-
sponding chiral secondary alcohol was obtained in 91% yield with
promising enantioselectivity (33% ee) when 6 was employed as the chiral
ligand. This showed that the catalytic reactivity of the chiral ligand in the
Scheme 2. Asymmetric Henry reaction catalyzed by Cu(OAc)2 ꢁ H2O–SAA
ligands (4 and 6).

SAA Ligands for Asymmetric Alkylation
3715
Scheme 3. Difference of the ligands’ structure (3 and 10) led to the changing of
the enantioselectivities in the catalytic reaction.
asymmetric Henry reaction was completely dependent on the structure of
the chiral ligand itself. Thus, it was encouraging that our catalytic system
could be efficient in other asymmetric transition processes. Further work
is under way in our laboratory.
In consideration of the possible mechanism, a similar ligand, 10, was
synthesized for the comparison with ligand 3 and then applied to the
asymmetric ethylation reaction. The (S)-product was obtained with only
3% ee when 10 was used (Scheme 3). This result suggested that the
hydroxyl group was essential for the catalytic efficiency.
On the basis of the well-known mechanism for asymmetric alkylation
of aldehydes with diethylzinc,[16,17] plausible canonical anti transition
states are proposed when the SAA ligands derived from different chiral
amino alcohols were used[18–21] (Fig. 2). Both the N-atom and the
Figure 2. Proposed transition states.

3716
J. Mao
O-atom of the amino alcohol, along with the N-atom from the sulfonamide
group, participate in the coordination with Zn to form an O,N,N-chelating
tridentate complex. From the catalytic efficiency of SAA ligands, we can
reason that the N-atom from the sulfonamide servers as another weakly
coordinative site in the cycle because it is a poor electron donor.[22] Thus,
based on the transition states TS-1 and TS-2 as the catalytically active
species, the SAA ligand 4 affords the (S)-enantiomer of the product, and
the SAA ligand 5 yields the (R)-enantiomer.
CONCLUSIONS
In summary, the novel sulfamide–amine alcohol ligands were readily
prepared in moderate yields in short synthetic sequences. These ligands
were evaluated in the asymmetric addition of diethylzinc to aldehydes,
which provided the chiral secondary alcohols with excellent yields and
good enantioselectivities in the absence of Ti(OiPr)4. Further work is in
progress in our laboratory with the aim of expanding the use of these
inexpensive chiral compounds to other enantioselective processes.
Experiments are under way to prove our plausible mechanism for the
asymmetric alkynylzinc addition of aldehydes.
EXPERIMENTAL
General
All reactions were carried out under an argon atmosphere. Solvents were
dried and degassed by the standard methods and organozinc reagent and
all aldehydes were purchased from Aldrich and Alfa. Flash-column
chromatography was performed by using silica gel (300–400 mesh).
Analytical thin-layer chromatography (TLC) was performed by using
glass plates precoated with 200- to 400-mesh silica gel impregnated with
a fluorescent indicator (254 nm). NMR spectra were measured in CDCl3
on a Varian Inova-400 NMR spectrometer (400 MHz or 300 MHz) with
tetramethylsilane (TMS) as an internal reference. Enantiomeric excess
(ee) determination was carried out using gas chromatography (GC) with
a chiral cyclodex b-2, 3, 6-M, 30-m ꢂ 0.32-mm capillary column on
an Agilent HP-4890 GC instrument with flame ionization detector
(FID), and high-performance liquid chromatography (HPLC) was done
with a chiral OD-H column. High-resolution mass spectra (HRMS) were
measured with electron impact (EI).

SAA Ligands for Asymmetric Alkylation
3717
General Procedure for Preparation of Sulfamide–Amine Alcohol 1
(S)-2-Phenyl-1-tosylaziridine 7 (1.0 g, 3.66 mmol) and chiral amino
alcohol 8 (0.8 g, 3.80 mmol) were dissolved in dry acetonitrile (30 mL),
and the mixture was stirred under reflux for 18 h. The solvent was
evaporated under reduced pressure. The residue was purified by column
chromatography on silica gel (eluent:petroleum ether=ethyl acetate ¼
1=1) to give the corresponding ligand 1 as white solid (0.8 g), 45% yield.
Ligands 2–4 were prepared analogously.
When (1R,2S)-cis-1-amino-2-indanol (9) was used as the chiral
amino alcohol, ligands 5 and 6 were obtained with this procedure.
When (R)-1-phenylethanamine was employed instead of the chiral
amino alcohol, ligand (10) was obtained.
Data
Ligand 1
25
White solid, 45% yield, ½aꢃD ¼ ꢄ26.3 (c ¼ 2.0 in MeOH); 1H NMR
(CDCl3) d: 2.35 (s, 3H), 2.52 (d, J ¼ 7.2 Hz, 2H), 3.62 (d, J ¼ 8.4 Hz,
1H), 4.18 (s, 1H), 4.68 (d, J ¼ 8.8 Hz, 1H), 5.55 (s, 1H), 6.96–6.99 (m,
2H), 7.07–7.14 (m, 8H), 7.22–7.30 (m, 7H), 7.46 (d, J ¼ 10.8 Hz, 2H);
13C NMR (CDCl3) d: 21.9, 52.9, 57.5, 69.4, 77.8, 126.9, 127.1, 127.5,
127.9, 128.3, 128.3, 128.6, 128.8, 129.8, 137.7, 139.4, 139.5, 140.8,
143.4; MS m=z: 379.1484 (69, M–C7H7O), 155.0206 (80, C7H7O2S),
106.0420 (55, C7H6O), 105.0337 (66, C7H6O), 91.0564 (100, C7H7).
Ligand 2
25
White solid, 38% yield, ½aꢃD ¼ þ27.2 (c ¼ 2.0 in MeOH); 1H NMR
(CDCl3) d: 2.35 (s, 3H), 2.52 (d, J ¼ 7.6 Hz, 2H), 3.63 (d, J ¼ 8.4 Hz,
1H), 4.18 (s, 1H), 4.69 (d, J ¼ 8.4 Hz, 1H), 5.51 (s, 1H), 6.96–6.99 (m,
2H), 7.07–7.14 (m, 11H), 7.23–7.37 (m, 4H), 7.46 (d, J ¼ 11.2 Hz, 2H);
13C NMR (CDCl3) d: 21.9, 52.9, 57.5, 69.3, 77.8, 126.9, 127.1, 127.5,
127.9, 128.3, 128.6, 128.8, 129.8, 137.7, 139.5, 140.8, 143.4; MS m=z:
379.1485 (69, M–C7H7O), 155.0208 (75, C7H7O2S), 106.0411 (51,
C7H6O), 105.0347 (63, C7H6O), 91.0554 (100, C7H7).
Ligand 3
25
White solid, 42% yield, ½aꢃD ¼ þ18.6 (c ¼ 3.0 in MeOH); 1H NMR (CDCl3) d:
2.36 (s, 3H), 2.58 (d, J¼ 8.4 Hz, 1H), 2.71 (d, J¼ 8.0 Hz, 1H), 3.88 (s, 1H),

3718
J. Mao
4.31 (s, 1H), 4.88 (s, 1H), 5.92 (brs, 2H), 6.95–7.03 (m, 4H), 7.09–7.24 (m,
12H), 7.55 (d, J¼ 8.0 Hz, 2H); 13C NMR (CDCl3) d: 21.9, 52.4, 57.2, 68.1,
77.0, 127.0, 127.2, 127.6, 127.9, 128.0, 128.2, 128.4, 128.7, 128.7, 129.8,
137.8, 139.1, 140.7, 143.5; MS m=z: 379.1491 (56, M–C7H7O), 155.0195 (74,
C7H7O2S), 106.0421 (36, C7H6O), 105.0350 (47, C7H6O), 91.0559 (100, C7H7).
Ligand 4
25
White solid, 47% yield, ½aꢃD ¼ ꢄ25.0 (c ¼ 2.0 in MeOH); 1H NMR
(CDCl3) d: 1.80 (brs, 2H), 2.37 (s, 3H), 2.55 (d, J ¼ 8.4 Hz, 1H), 2.66
(d, J ¼ 9.0 Hz, 1H), 3.80 (s, 1H), 4.27 (s, 1H), 4.80 (s, 1H), 5.68 (brs,
1H), 6.95–7.26 (m, 13H), 7.54 (d, J ¼ 5.1 Hz, 2H); 13C NMR (CDCl3)
d: 21.9, 52.6, 57.4, 68.3, 77.4, 127.0, 127.2, 127.6, 127.9, 128.2, 128.5,
128.6, 128.8, 128.8, 137.8, 138.5, 139.3, 140.8, 143.5; MS m=z: 379.1494
(60, M–C7H7O), 155.0198 (78, C7H7O2S), 106.0414 (47, C7H6O),
105.0347 (57, C7H6O), 91.0558 (100, C7H7).
Ligand 5
25
White solid, 42% yield, ½aꢃD ¼ ꢄ1.5 (c ¼ 2.3 in MeOH); 1H NMR (CDCl3)
d: 1.92 (brs, 2H), 2.36 (s, 3H), 2.86–3.12 (m, 4H), 3.97 (d, J ¼ 6.4 Hz, 1H),
4.35–4.43 (m, 2H), 5.30 (s, 1H), 7.14–7.22 (m, 11H), 7.61 (d, J ¼ 10.8 Hz,
2H); 13C NMR (CDCl3) d: 20.9, 30.7, 52.9, 57.7, 65.3, 70.9, 124.3, 124.8,
125.9, 126.4, 126.8, 127.0, 127.9, 129.2, 138.7, 140.8, 140.9, 142.1, 143.5;
MS m=z: 379.1490 (7, M–C2H3O), 155.0209 (75, C7H7O2S), 106.0414
(47, C7H6O), 129.0614 (71, C9H7N), 91.0556 (100, C7H7).
Ligand 6
25
White solid, 40% yield, ½aꢃD ¼ þ40.5 (c ¼ 2.0 in MeOH); 1H NMR (CDCl3)
d: 1.71 (brs, 2H), 2.34 (s, 3H), 2.85–3.11 (m, 4H), 3.95 (d, J¼ 4.8 Hz, 1H),
4.38–4.43 (m, 2H), 5.48 (s, 1H), 7.11–7.27 (m, 11H), 7.59 (d, J¼ 10.2 Hz,
2H); 13C NMR (CDCl3) d: 21.9, 40.1, 53.8, 58.0, 65.9, 71.8, 124.7, 126.0,
127.2, 127.3, 127.6, 128.2, 128.6, 129.0, 129.9, 137.6, 138.5, 141.0, 142.3, 143.7.
Ligand 10
White solid, 55% yield; 1H NMR (CDCl3) d: 1.27 (d, J ¼ 5.1 Hz, 3H), 2.37
(s, 3H), 2.52–2.81 (m, 2H), 3.53–3.57 (m, 1H), 4.27–4.30 (m, 1H),
7.06–7.32 (m, 12H), 7.60 (d, J ¼ 5.7 Hz, 2H); 13C NMR (CDCl3) d: 21.9,

SAA Ligands for Asymmetric Alkylation
3719
24.5, 52.7, 57.1, 57.5, 126.8, 127.1, 127.6, 127.7, 127.9, 128.7, 129.1, 129.8,
137.7, 139.6, 143.6, 144.7.
General Procedures for the Asymmetric Addition of Et2Zn to Aldehydes
Under a dry argon atmosphere, chiral ligand (10 mol%, 0.05 mmol) in dry
toluene (4 mL) was cooled to 0ꢀC and a solution of Et2Zn (1.0 M in
hexane, 1.1 mmol) was added slowly. After stirring for 30 min at 0ꢀC,
freshly distilled aldehyde (0.5 mmol) was added, and the reaction was
stirred for 24 h at 10ꢀC. The reaction mixture was quenched with 1 N
aqueous HCl at 0ꢀC. The aqueous phase was extracted with ethyl acetate
(3 ꢂ 5 mL). The combined organic phase was washed with little brine,
dried with anhydrous Na2SO4, filtered, and concentrated. The residue
was purified by flash-column chromatography on silica gel (petroleum
ether–ethyl acetate ¼ 12:1) to give the carbinol. The enantiomeric purity
of the product was determined by HPLC. The absolute configurations
of the products were assigned by comparison to literature values.
General Procedures for the Asymmetric Henry Reaction Between
4-Nitrobenzaldehyde and Nitromethane
Chiral ligand (10 mol%, 0.02mmol) and Cu(OAc)2 ꢁ H2O (4.0 mg,
0.02 mmol) were added to isopropanol (2.0 mL) at room temperature in
air. The reaction mixture was stirred for 30min, and then 4-nitrobenzalde-
hyde (30.2mg, 0.2 mmol) and nitromethane (0.3 mL) were added to the
resulting blue solution. The mixture was stirred for 48 h at room tempera-
ture and then concentrated in vacuo to give a glutinous phase residue. Next,
CH2Cl2 (2.0 mL) and aqueous HCl solution (1.0 M, 5 mL) were added into
the residue, and the mixture was stirred until the green color disappeared.
After extraction with CH2Cl2 (3 ꢂ 10mL), the combined organic layers were
washed with brine, dried over anhydrous Na2SO4, and evaporated in vacuo.
The residue was purified by flash chromatography on silica gel (petroleum
ether–ethyl acetate ¼ 8:1) to afford the corresponding chiral product.
Data
2-Nitro-1-(4-nitrophenyl)ethanol
Yield 91%. Ee (33%) determined by HPLC analysis (Chiralcel OD-H column,
IPA–hexane ¼ 8:92). Retention time: tmajor ¼ 16.71 min, tminor ¼ 18.64 min.

3720
J. Mao
1H NMR (400 MHz, CDCl3): d 3.23 (d, J¼ 4.0 Hz, 1H), 4.57 (dd, J¼ 4.0,
13.8 Hz, 1H), 4.61 (dd, J¼ 8.4, 13.6 Hz, 1H), 5.62 (dd, J¼ 3.6, 12.0 Hz,
1H), 7.63 (d, J¼ 8.8 Hz, 2H), 8.28 (d, J¼ 8.8 Hz, 2H).
ACKNOWLEDGMENTS
We are grateful to the grants from the National Natural Science
Foundation of China (No. 20802046) and the Key Laboratory of Organic
Synthesis of Jiangsu Province for financial support.
REFERENCES
1. (a) Soai, K.; Shibata, T. In Comprehensive Asymmetric Catalysis; E.N.
Jacobsen, A. Pfaltz, H. Yamamoto, (Eds.); Springer: Berlin, 1999; pp.
911–922; (b) Noyori, R. Asymmetric Catalysis in Organic Synthesis; Wiley:
New York, 1994; (c) Ojima, I. Catalytic Asymmetric Synthesis, 2nd ed.;
Wiley-VCH: New York, 2000.
2. Brunner, H.; Zettlmeier, W. Handbook of Enantioselective Catalysis; VCH:
New York, 1993; vols. 1–2.
3. Pu, L.; Yu, H. B. Catalytic asymmetric organozinc additions to carbonyl
compounds. Chem. Rev. 2001, 10, 757.
4. Soai, K.; Niwa, S. Enantioselective addition of organozinc reagents to
aldehydes. Chem. Rev. 1992, 92, 833.
5. Noyori, R.; Kitamura, M. Enantioselective addition of organometallic
reagents to carbonyl compounds: Chirality transfer, multiplication, and
amplification. Angew. Chem., Int. Ed. Engl. 1991, 30, 49.
6. Balsells, J.; Walsh, P. J. Design of diastereomeric self-inhibiting catalysts for
control of turnover frequency and enantioselectivity. J. Am. Chem. Soc. 2000,
122, 3250.
ꢀ
7. Ramon, D. J.; Yus, M. First enantioselective addition of dialkylzinc to
ketones promoted by titanium (IV) derivatives. Tetrahedron Lett. 1998, 39,
1239.
8. Hwang, C. D.; Uang, B. J. Enantioselective addition of diethylzinc to
aldehydes induced by a new chiral Ti(IV) catalyst. Tetrahedron: Asymmetry
1998, 9, 3979.
9. Ito, K.; Kimura, Y.; Okamura, H.; Katsuki, T. Enantioselective addition of
diethylzinc to aldehydes in the presence of chiral titanium reagent modified
with n-sulfonylated amino alcohol. Synlett 1992, 573.
10. Mao, J.; Wan, B.; Wang, R.; Wu, F.; Lu, S. Concise synthesis of novel
practical sulfamide–amine alcohols for the enantioselective addition of
diethylzinc to aldehydes. J. Org. Chem. 2004, 69, 9123.
11. Mao, J.; Wan, B.; Zhang, Z.; Wang, R.; Wu, F.; Lu, S. Reversal of enantio-
selectivity by adding Ti(OiPr)4: Novel sulfamide–amine alcohol ligands for

SAA Ligands for Asymmetric Alkylation
3721
the catalytic asymmetric addition of diethylzinc to aldehydes. J. Mol. Catal.
A: Chem. 2005, 225, 33.
12. Bieber, L. W.; de Arau´jo, M. C. F. Short and efficient synthesis of optically
active n-tosyl aziridines from 2-amino alcohols. Molecules 2002, 7, 902.
13. (a) Xu, Z.; Mao, J.; Zhang, Y. Highly enantioselective alkynylation of alde-
hydes catalyzed by a new oxazolidine–titanium complex. Org. Biomol. Chem.
2008, 6, 1288; (b) Mao, J.; Wan, B.; Wu, F.; Lu, S. First example of asym-
metric transfer hydrogenation in water induced by a chiral amino alcohol
hydrochloride. Tetrahedron Lett. 2005, 46, 7341; (c) Mao, J.; Wan, B.; Wu,
F.; Wang, R.; Lu, S. Sulfamide–amine alcohol catalyzed enantioselective
alkynylation of aromatic ketones. J. Mol. Catal. A: Chem. 2005, 237, 126;
(d) Mao, J.; Wan, B.; Wu, F.; Lu, S. Readily available sulfamide–amine alco-
hols for enantioselective phenylacetylene addition to aldehydes in the absence
of Ti(OiPr)4. Chirality 2005, 17, 245.
14. Vogl, E. M.; Groger, H.; Shibasaki, M. Towards perfect asymmetric cataly-
sis: additives and cocatalysts. Angew. Chem. Int. Ed. 1999, 38, 1570.
15. Bolm, C.; Rudolph, J. Catalyzed asymmetric aryl transfer reactions to alde-
hydes with boronic acids as aryl source. J. Am. Chem. Soc. 2002, 124, 14850.
16. Kitamura, M.; Suga, S.; Oka, H.; Noyori, R. Quantitative analysis of the
chiral amplification in the amino alcohol–promoted asymmetric alkylation
of aldehydes with dialkylzincs. J. Am. Chem. Soc. 1998, 120, 9800.
17. Yamakawa, M.; Noyori, R. Asymmetric addition of dimethylzinc to benzal-
dehyde catalyzed by (2S)-3-exo-(dimethylamino)isobornenol: A theoretical
study on the origin of enantioselection. Organometallics 1999, 18, 128.
18. Huang, J.; Lanni, J. C.; Antoline, J. E.; Hsung, R. P.; Kozlowski, M.C. De
novo chiral amino alcohols in catalyzing asymmetric additions to aryl
aldehydes. Org. Lett. 2006, 8, 1565.
19. Rasmussen, T.; Norrby, P. O. Modeling the stereoselectivity of the b-amino
alcohol-promoted addition of dialkylzinc to aldehydes. J. Am. Chem. Soc.
2003, 125, 5130.
20. Vazquez, J.; Pericas, M. A.; Maseras, F.; Lledos, A. A quantum mechan-
ics=molecular mechanics study of the highly enantioselective addition of
diethylzinc to benzaldehyde promoted by (R)-2-piperidino-1,1,2-
triphenylethanol. J. Org. Chem. 2000, 65, 7303.
21. Goldfuss, B.; Houk, K. N. Origin of enantioselectivities in chiral b-amino
alcohol catalyzed asymmetric additions of organozinc reagents to benzalde-
hyde: PM3 transition state modeling. J. Org. Chem. 1998, 63, 8998.
22. Pritchett, S.; Gantzel, P.; Walsh, P. J. Synthesis and crystal structures of
chiral titanium bis(sulfonamido) bis(amide) complexes: Differences in ligand
hapticity caused by crystal packing forces. Organometallics 1997, 16, 5130.