Indium-catalyzed enantioselective allylation of aldehydes with β-carbonyl allylstannanes: An efficient synthetic method for chiral α-methylene-γ-lactones

Article abstract of DOI:10.1016/j.jorganchem.2009.09.037

The catalytic enantioselective allylation of aldehydes with β-carbonyl allyltributylstannanes in the presence of chiral indium complexes gave the optically active homoallylic alcohols, which can be converted to the corresponding optically active α-methyle

Full text of DOI:10.1016/j.jorganchem.2009.09.037

Journal of Organometallic Chemistry 695 (2010) 128–136
Contents lists available at ScienceDirect
Journal of Organometallic Chemistry
journal homepage: www.elsevier.com/locate/jorganchem
Indium-catalyzed enantioselective allylation of aldehydes with b-carbonyl
allylstannanes: An efficient synthetic method for chiral
a-methylene-c-lactones
*
Takamasa Suzuki, Jun-ichi Atsumi, Tetsuya Sengoku, Masaki Takahashi, Hidemi Yoda
Department of Materials Science, Faculty of Engineering, Shizuoka University, Johoku 3-5-1, Naka-ku, Hamamatsu 432-8561, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The catalytic enantioselective allylation of aldehydes with b-carbonyl allyltributylstannanes in the pres-
ence of chiral indium complexes gave the optically active homoallylic alcohols, which can be converted to
Received 26 August 2009
Received in revised form 10 September
2009
Accepted 25 September 2009
Available online 4 October 2009
the corresponding optically active
a
-methylene-
c-butyrolactones.
Ó 2009 Elsevier B.V. All rights reserved.
Keywords:
Enantioselective allylation
Indium catalyst
b-Carbonyl allylstannane
a-Methylene-c-lactone
1. Introduction
tyltin to the dianion solution of 2 prepared from N-phenyl meth-
acrylamide (1) according to our preceding literature [4d].
Asymmetric allylation of aldehydes is one of the most efficient
methods to prepare the chiral homoallylic alcohols [1–3] which are
the versatile building blocks for creating an abundant of biologically
important compounds. Allylsilanes and allylstannanes have been
used as potential reagents for allylation reactions due to their fasci-
nating and excellent reactivity, effectively achieving catalytic asym-
metric alkylation in the nucleophilic processes. Although a large
number of these reactions employing reagents without functional
groups have been reported to date, to the best of our knowledge, only
few examples of allylation reactions with b-carbonyl allylstannanes
have appeared in the literature [4]. Recently, we reported the first
example of enantioselective allylation between b-amido allyltribu-
tylstannanes and aldehydes in the presence of [In(S,S)-iPr-pybox]-
2.2. Enantioselective allylation of benzaldehyde (5a) with
allyltrimethylsilane (3) and allyltributylstannane (4a)
To examine whether allylating reagents work, we attempted
the reactions of 3 and 4a with benzaldehyde (5a) in the presence
of In(OTf)3 [6] (Table 1). Under the conditions employing catalytic
and stoichiometric amounts of In(OTf)3 in CH2Cl2 at ambient tem-
perature, 3 failed to react with 5a and was recovered intact. By
contrast, 4a reacted smoothly (8 h) in the presence of 30 mol% of
In(OTf)3 to afford c-hydroxy amide 6 in 89% yield (entry 1). Having
assured the sufficient reactivity of the b-carbonyl allyltributylst-
annane, we turned our attention to the development of catalytic
asymmetric allylation with 4a. As for the chiral source, we chose
(S)-4-isopropyl-2,6-bis(oxazolin-2-yl)pyridine 7a ([M(S,S)-iPr-py-
box]X3) because a number of examples that lead to high enantio-
meric yields of products have recently been achieved, making
this molecule an excellent candidate for the chiral ligand [6]. By
use of 30 mol% of the chiral ligand, the optically active 6 was
formed enantioselectively with 81% yield and 37% ee (Table 1, en-
try 2) [7]. With the catalyst loads from 10 to 30 mol% (Table 1,
entries 2–4), this allylation reaction proceeded efficiently (72–
96% yield and 37–63% ee) whereas in the presence of 5 mol% of cat-
alyst, the reaction resulted in only 41% yield of the desired product
with 53% ee. On the other hand, there are no significant effects of
adding TMSCl [6a] in enantiomeric yields of products (entry 6),
while the use of alternative ligands, neither 7b nor 7c [8] led to
(OTf)3, which afforded chiral
c-hydroxy amides in high chemical
and enantiomeric yields (Scheme 1) [4a]. In this paper, we present
the details of our studies on the catalytic enantioselective allylation
with several types of b-carbonyl allyltributylstannanes, applying to
thepreparation of optically active a-methylene-c-butyrolactones [5].
2. Results and discussion
2.1. Preparation of allylating reagents
As shown in Scheme 2, b-substituted allylating reagents 3 and
4a were generated by adding chlorotrimethylsilane or chlorotribu-
* Corresponding author. Tel./fax: +81 53 478 1150.
E-mail address: tchyoda@ipc.shizuoka.ac.jp (H. Yoda).
0022-328X/$ - see front matter Ó 2009 Elsevier B.V. All rights reserved.
doi:10.1016/j.jorganchem.2009.09.037

T. Suzuki et al. / Journal of Organometallic Chemistry 695 (2010) 128–136
129
O
O
N
N
N
In
(OTf)3
iPr
iPr
R1HN
O
[In(S,S)-iPr-pybox](OTf)3 (10 mol%)
R1HN
O
OH
R2
aldehyde
(R2CHO)
+
SnBu3
CH2Cl2, MS 4Å, rt
up to 96% yield
up to 79% ee
Scheme 1. Catalytic enantioselective allylation of aldehydes with b-amido allyltributylstannanes in the presence of [In(S,S)-iPr-pybox](OTf)3.
Using allylstannane 4f that afforded the best enantiomeric
yield, we investigated the allylation reaction with various alde-
hydes 5b–j under the same reaction conditions as employed in Ta-
ble 2. Table 3 shows that the reactions with the aliphatic aldehydes
5b and 5c gave moderate enantiomeric excesses and relatively low
chemical yields (entries 2 and 3). A modest improvement in the
asymmetric allylation was observed for aromatic aldehydes 5d–j,
which resulted in better yields of the desired products (entries
4–10). In particular, the reaction with isopropyl-substituted N-
phenyl derivative 5g was found to give the highest enantiomeric
excess (79% ee) and sufficiently high chemical yield (94%).
PhHN
O
PhN
O
PhHN
O
a
b or c
X
1
2
3: X = SiMe3
4a: X = SnBu3
Scheme 2. Reagents and conditions: (a) t-BuOK, THF, ꢀ78 °C, 1 h, then n-BuLi,
ꢀ78 °C, 13 min; (2); (b) Me3SiCl, THF, -78 °C, 1 h, ꢀ0 °C, 3 h; 89% (3) (two steps); (c)
n-Bu3SnCl, THF, ꢀ78 °C, 1 h; 77% (4a) (two steps).
give further improvements in the enantiomeric excesses (entries 7
and 8).
Through treatment with 10% HCl in 1,4-dioxane, the
amides 12, 15 and 20–23 underwent efficient formation of
methylene- -butyrolactones 24–29 without loss of enantiomeric
c-hydroxy
a-
Next, we further investigated the same catalytic asymmetric
allylation with other N-substituted b-amido allyltributylstannanes
4b–h prepared from the corresponding N-substituted methacryla-
mides as mentioned above (Table 2). Under the optimal reaction
conditions for 4a, N-aliphatic reagents 4b and 4c gave optically ac-
tive adducts 8 and 9 with 26% and 39% ee, respectively (entries 2
and 3). It should be noted that the reactions of N-aromatic ana-
logues 4d and 4e proceeded with attractive enantiomeric yields
(63% and 70% ee) under the identical conditions and 4-tert-butyl-
substituted N-phenyl derivative 4f gave the highest enantiomeric
excess (77% ee) together with the satisfactory chemical yield
(81%). In contrast, the reactions with methoxy-substituted N-phe-
nyl derivatives 4g and 4h resulted in loss of the enantioselectivities
with 9.1% and 0.2% ee, respectively.
c
purity [4d] in the yields ranging from 79% to 99% yields, respec-
tively (Scheme 3).
2.3. Enantioselective allylation of benzaldehyde (5a) with b-
alkoxycarbonyl allyltributylstannanes 31–35
Having elucidated details of the enantioselective allylation with
a series of b-amido allyltributylstannanes, we next focussed on the
reaction with b-alkoxycarbonyl versions 31–35. These substrates
were obtained by the substitution reactions of 30 [10] with the
corresponding alkoxides. Complex 30 was prepared from 4a via
Table 1
Enantioselective allylation of benzaldehyde (5a) with allyltributylstannane 4a in the presence of chiral catalysts.a
cat. In(OTf)3/chial ligands
PhHN
O
PhHN
O
benzaldehyde (5a)
O
O
OH
OH
OH
N
SnBu3
N
N
CH2Cl2, MS 4Å, rt
R
R
6
4a
pybox
BINOL 7c
(R = iPr (7a), Ph (7b))
Entry
In(OTf)3 (mol%)
Chiral ligands
TMSCl (equiv.)
% yield of 6b
% eec (confign)d
1
2
3
4
5
6
7
8
30
30
20
10
5
10
10
10
–
–
–
–
–
–
1.2
–
89
81
72
96
41
85
96
90
–
iPr-pybox (7a)
iPr-pybox (7a)
iPr-pybox (7a)
iPr-pybox (7a)
iPr-pybox (7a)
Ph-pybox (7b)
BINOL (7c)
37 (S)
51 (S)
63 (S)
53 (S)
32 (S)
49 (S)
21 (S)
–
a
b
c
All reactions were carried out in the presence of activated MS 4Å (120 mg) in CH2Cl2 (0.2 mol/L) at ambient temperature.
Isolated yield.
Determined by chiral HPLC analysis using Daicel Chiralpak IB and IC columns.
Predicted configurations, see Refs. [5k,9].
d

130
T. Suzuki et al. / Journal of Organometallic Chemistry 695 (2010) 128–136
Table 2
Enantioselective allylation of benzaldehyde (5a) with 4a–h in the presence of 10 mol% of [In(S,S)-iPr-pybox](OTf)3.a
O
[In(S,S)-iPr-pybox](OTf)3 (10 mol%)
RHN
O
RHN
O
OH
+
H
SnBu3
CH2Cl2, MS 4Å, rt
4a-h
5a
6 8 14
,
-
Entry
R (4: allystannanes)a
% yield (adducts)b
% eec (confign)d
1e
2
3
4
5
6
7
8
Phenyl (4a)
96 (6)
88 (8)
78 (9)
74 (10)
78 (11)
81 (12)
78 (13)
56 (14)
63 (S)
26 (S)
39 (S)
63 (S)
70 (S)
77 (S)
9.1 (S)
0.2 (S)
tert-Butyl (4b)
Cyclohexyl (4c)
3-Biphenyl (4d)
3,5-Di-tert-butylphenyl (4e)
4-tert-Butylphenyl (4f)
2-Methoxyphenyl (4g)
4-Methoxyphenyl (4h)
a
b
c
All reactions were carried out in the presence of activated MS 4Å (120 mg) in CH2Cl2 (0.2 mol/L) at ambient temperature.
Isolated yield.
Determined by chiral HPLC analysis using Daicel Chiralpak IB and IC columns.
Predicted configurations, see Refs. [5k,9].
See Table 1.
d
e
Table 3
Enantioselective allylation of aldehyde 5 with 4f in the presence of 10 mol% of [In(S,S)-iPr-pybox](OTf)3.a
Entry
R (5: aldehydes)
% yield (adducts)b
% eec (confign)d
1e
2
3
4
5
6
7
8
9
Phenyl (5a)
Isobutyl (5b)
tert-Butyl (5c)
4-Methoxyphenyl (5d)
3-Chlorophenyl (5e)
4-Nitrophenyl (5f)
4-Isopropylphenyl (5g)
4-tert-Butylphenyl (5h)
1-Naphthyl (5i)
78 (12)
45 (15)
45 (16)
79 (17)
90 (18)
79 (19)
94 (20)
81 (21)
94 (22)
94 (23)
77 (S)
47 (R)
58 (R)
59 (S)
61 (S)
58 (S)
79 (S)
61 (S)
68 (S)
74 (S)
10
2-Naphthyl (5j)
a
b
c
All reactions were carried out in the presence of activated MS 4Å (120 mg) in CH2Cl2 (0.2 mol/L) at ambient temperature.
Isolated yield.
Determined by chiral HPLC analysis using Daicel Chiralpak IB or IC columns.
Predicted configurations, see Refs. [4d,5k,9].
See Table 2.
d
e
rolactone 24 was directly obtained in 53% yield without isolation
of the corresponding homoallylic alcohol (Table 4, entry 1). After
purification by column chromatography, the product 24 proved
to be almost racemic (2.1% ee, entry 1).
Whereas replacement of In(OTf)3 with InCl3 [8] under same
conditions led to production of only trace amount of 24 detected
on TLC (entry 2), the use of the chiral ligand 7c [8] instead of 7a
led to form the optically active 24 with 94% yield and 14% ee (entry
3). When reducing the amount of catalyst (15 mol%), enantioselec-
tivity was significantly improved (58% ee, entry 4). Under identical
conditions, the allylation reactions with other b-alkoxycarbonyl
allyltributylstannanes 32–35 exhibited significant levels of enanti-
oselectivity and afforded 24 with up to 53% ee (entries 5–8).
H
N
O
10% HCl
OH
O
tBu
R
R
1,4-dioxane, 65 °C
O
12
24
: R = C6H5
: R = C6H5 (99%)
15: R = iBu
25: R = iBu (83%)
20: R = (4-iPr)C6H4
26: R = (4-iPr)C6H4 (79%)
t
t
21
27
: R = (4- Bu)C6H4
: R = (4- Bu)C6H4 (88%)
28: R = 1-Naphthyl (92%)
29: R = 2-Naphthyl (91%)
22: R = 1-Naphthyl
23: R = 2-Naphthyl
Scheme 3. Synthesis of
a-methylene-
c
-butyrolactones 24–29 by acidic hydrolysis.
Boc-protection of the secondary amide group under basic condi-
tions (Scheme 4).
2.4. Mechanistic interpretation for the asymmetric allylation
When the allylation reaction between 5a and 31 was performed
The asymmetric allylation would be explained on the basis of
chiral coordination environment created by the isopropyl groups
in the presence of [In(S,S)-iPr-pybox](OTf)3,
a-methylene-c-buty-

T. Suzuki et al. / Journal of Organometallic Chemistry 695 (2010) 128–136
131
PhHN
O
Ph(Boc)N
O
a
SnBu3
SnBu3
O
O
O
O
N
N
OTf
OTf
4a
30
N
TfO
O
N
N
TfO
O
N
In
In
O
O
RO
O
b or c
R2
H
SnBu3
R1
R1
H
R2
CH2SnBu3
N
H
N
H
CH2SnBu3
31-35
(R = Et, Me, iPr, Bn, Ph)
Model A
Model B
Scheme 4. Reagents and conditions: (a) Boc2O, Et3N, DMAP, CH2Cl2, r.t., 18 h; 98%
(30); (b) NaH, ROH, 0 °C to r.t.; 92% (31; R = Et); 67% (32; R = Me); (c) NaH, ROH,
THF, r.t.; 68% (33; R = iPr); 64% (34; R = Bn); 57% (35; R = Ph).
Fig. 1. Plausible transition models of b-amido allyltributylstannanes 4.
of the rigid pybox ligand. Typically, three of the six available In3+
octahedral coordination sites are bound by the chelation of three
nitrogen atoms in the chiral ligand, leaving three sites available
for the two carbonyl functions of b-amido allyltributylstanannes
and aldehydes. Due to the fact that the aldehydes are less sterically
congested than the b-amido allyltributylstanannes, the formers
can coordinate the In3+ complex at a less crowded disposition as
illustrated in Fig. 1, while destabilizing steric interactions between
the tributylstannylmethyl groups and isopropyl moieties of the py-
box ligand should be minimized. In such a case, the aldehyde mol-
ecules would adopt low-energy conformation that decreases steric
hindrance created by the isopropyl moieties (Model A) rather than
more sterically demanding conformation (Model B). Hence, the
nucleophilic attack between the flexible allylic arms and the car-
bonyl carbons proceeded enantioselectively through the asymmet-
ric transition state, leading to the observed absolute configurations
of the products with the moderate enantiomeric yields.
On the other hand, similar mechanistic rationale could explain
the observed results for the use of the In3+-binaphthol catalyst.
For steric reasons, the catalyst-reactant chelates would prevent
conformations with the aromatic ring of the aldehyde locating at
closer disposition of the bulky binaphthyl moieties. Based on this
consideration, two conformational models could be proposed to
satisfy geometrical requirement for the occurrence of the allylation
reactions (Models C and D in Fig. 2). It was anticipated that the lar-
ger tributylstannylmethyl substituent should be oriented away
from the steric crowding present at the molecular edges of the
binaphthyl ligand, suggesting that the thermodynamically more
OR
CH2SnBu3
H
CH2SnBu3
O
O
O O
O
H
O
In
Cl
In
Cl
Ph
O
Ph
O
OR
Model C
Model D
Fig. 2. Plausible transition models of the b-alkoxycarbonyl allyltributylstannanes.
favored conformation (Model C) should be formed in the reaction
as the major transition state relative to the other (Model D). The
experimental data concerning the product stereochemistry are in
good agreement with the conformational model in which all the
absolute stereocenters created at the hydroxy-bearing carbon
atom proved to be S.
3. Conclusion
We have demonstrated the details of catalytic enantioselective
allylation of various aldehydes with b-carbonyl allyltributylstann-
anes in the presence of 10 mol% of [In(S,S)-iPr-pybox](OTf)3 or
15 mol% of [In(S)-BINOL]Cl3 complexes, respectively. The reactions
between N-aryl b-amido allyltributylstannanes and aromatic alde-
hydes were found to be effective, giving high enantioselectivity. On
Table 4
Enantioselective allylation and cyclization sequence of benzaldehyde (5a) with 31–35 catalyzed by chiral indium(III) catalysts.
Entry
R
Indium
Chiral ligand
mol%
% yield of 24a
% eeb (confign)c
1
2
3
4
5
6
7
8
Et (31)
Et (31)
Et (31)
Et (31)
Me (32)
iPr (33)
Bn (34)
Ph (35)
In(OTf)3
InCl3
InCl3
InCl3
InCl3
InCl3
InCl3
InCl3
iPr-pybox (7a)
iPr-pybox (7a)
BINOL (7c)
BINOL (7c)
BINOL (7c)
BINOL (7c)
BINOL (7c)
BINOL (7c)
30
30
30
15
15
15
15
15
53
trace
94
93
96
90
64
78
2.1 (S)
NDd
14 (S)
58 (S)
39 (S)
25 (S)
53 (S)
45 (S)
a
b
c
Isolated yield.
Determined by chiral HPLC analysis using Daicel Chiralpak IC column.
Predicted configurations, see Ref. [5k].
Not determined.
d

132
T. Suzuki et al. / Journal of Organometallic Chemistry 695 (2010) 128–136
the other hands, the reaction of b-alkoxycarbonyl allyltributylst-
annanes and benzaldehyde provided directly the corresponding
3.3 Hz, 1H, CH), 4.46 (d, J = 3.3 Hz, 1H, OH), 2.75 (dd, J = 14.2,
3.4 Hz, 1H, CH2), 2.65 (dd, J = 14.2, 8.3 Hz, 1H, CH2); 13C NMR
(CDCl3) d 172.5 (C), 144.5 (C), 144.3 (C), 140.4 (C), 129.4 (CH),
128.2 (CH), 127.2 (CH), 127.1 (CH), 126.6 (CH), 125.7 (CH2), 122.7
(CH), 74.1 (CH), 44.8 (CH2). Anal. Calc. for C28H27NO4: C, 76.17; H,
6.16; N, 3.17; Found: C, 76.43; H, 6.81; N, 5.30%.
a
-methylene-
advantages of being not only catalytic and enantioselective in the
allylation, but able to give optically active -methylene- -butyro-
c-butyrolactones. These methods possess desirable
a
c
lactones without employing chiral allyltributylstannanes prepared
through tedious elaboration [4c,4d].
4.2.1.1.
(S)-N-tert-Butyl-4-hydroxy-2-methylene-4-phenylbutana-
mide (8). M.p. 110.4–110.9 °C; ½a D23
ꢀ13.3 (c 2.43, CHCl3); IR
ꢁ
4. Experimental
(KBr) 3360 (N–H), 2970 (O–H), 1651 (C@O) cmꢀ1; 1H NMR (CDCl3):
d 7.35–7.19 (m, 5H, ArH), 6.18 (brs, 1H, NH), 5.51 (s, 1H, CH2), 5.38
(d, J = 3.4 Hz, 1H, OH), 5.16 (s, 1H, CH2), 4.77 (dt, J = 8.3, 3.4 Hz, 1H,
CH), 2.64 (dd, J = 13.9, 3.4 Hz, 1H, CH2), 2.53 (dd, J = 13.9, 8.3 Hz,
1H, CH2), 1.36 (s, 9H, CH3); 13C NMR (CDCl3): d 170.0 (C), 144.5
(C), 143.5 (C), 128.1 (CH), 127.0 (CH), 125.7 (CH), 120.0 (CH2),
74.4 (CH), 51.5 (C), 43.4 (CH2), 28.5 (CH3); HRMS (ESI+) m/z calcd
for C15H21NO2+Na: 270.1465, found 270.1446.
4.1. General
All solvents and reagents were of reagent grade quality from Al-
drich Chemical Company, Fluka, Acros or Wako Pure Chemicals and
used without any further purification. Melting points were mea-
sured on an automated melting point system (MPA 100, Stanford
Research Systems). Fourier transform infrared (FT-IR) spectra were
recorded on a Shimadzu FTIR-8200A spectrometer. The 1H- and
13C-nuclear magnetic resonance (NMR) spectra operating at the
frequencies of 300 and 75 MHz, respectively, were measured with
a JEOL JNM-AL300 spectrometer in chloroform-d (CDCl3) unless
otherwise stated. Chemical shifts are reported in parts per million
(ppm) relative to TMS as internal standard (d = 0 ppm) for 1H NMR,
and CDCl3 was used as internal standard (d = 77.0) for 13C NMR.
The coupling constants are reported in hertz (Hz). Optical rotations
were measured in 1 dm path length cell of 2 mL capacity using a
JASCO Model DIP-1000 polarimeter at a wavelength of 589 nm.
Reactions were monitored by thin-layer chromatography (TLC)
using 0.25 mm Merck silica gel 60-F254 precoated silica gel plates
by irradiation with UV light and/or by treatment with a solution
of phosphomolybdic acid in methanol followed by heating. Column
chromatography was performed on Kanto Chemical silica gel 60N
eluting with the indicated solvent system. The non-crystalline
compounds were shown to be homogeneous by chromatographic
methods and characterized by NMR, IR, high resolution mass spec-
tra (HRMS) and microanalysis. High-pressure liquid chromatogra-
phy (HPLC) was carried out using a Shimadzu Model LC-10AD or
10AT intelligent pump and SPD-10A UV detector. HRMS were re-
corded on a JEOL JMS-T100CS spectrometer. Microanalyses were
performed with a JSL Model JM 10.
4.2.1.2. (S)-N-Cyclohexyl-4-hydroxy-2-methylene-4-phenylbutana-
mide (9). M.p. 95.8–96.6 °C; ½a D19
ꢁ
ꢀ14.5 (c 1.00, CHCl3); IR (KBr)
3279 (N–H), 2855 (O–H), 1645 (C@O) cmꢀ1
;
1H NMR (CDCl3): d
7.36–7.19 (m, 5H, ArH), 6.29 (d, J = 7.5 Hz, 1H, NH), 5.55 (s, 1H,
CH2), 5.33 (d, J = 3.5 Hz, 1H, OH), 5.19 (s, 1H, CH2), 4.81 (ddd,
J = 8.1, 4.2, 3.5 Hz, 1H, CH), 3.77 (m, 1H, CH), 2.68 (dd, J = 13.9,
4.2 Hz, 1H, CH), 2.56 (dd, J = 13.9, 8.1 Hz, 1H, CH2), 1.94–1.90 (m,
2H, CH2), 1.74–1.59 (m, 3H, CH2), 1.40–1.11 (m, 5H, CH2); 13C
NMR (CDCl3): d 169.5 (C), 144.4 (C), 142.7 (C), 128.1 (CH), 127.1
(CH), 125.7 (CH), 120.5 (CH2), 74.3 (CH), 48.6 (CH), 43.4 (CH2),
32.8 (CH2), 25.4 (CH2), 24.7 (CH2). Anal. Calc. for C17H23NO2: C,
74.69; H, 8.48; N, 5.12. Found: C, 74.99; H, 8.60; N, 5.07%.
4.2.1.3. (S)-N-(3-Biphenyl)-4-hydroxy-2-methylene-4-phenylbutana-
mide (10). M.p. 147.2–148.1 °C; ½a D28
ꢁ
ꢀ19.7 (c 0.500, EtOH); IR
(KBr) 3202 (N–H), 3088 (O–H), 1616 (C@O) cmꢀ1
;
1H NMR (acet-
one-d6): d 9.61 (brs, 1H, NH), 8.08 (m, 1H, ArH), 7.77–7.21 (m,
13H, ArH), 5.93 (d, J = 0.8 Hz, 1H, CH2), 5.46 (d, J = 0.9 Hz, 1H,
CH2), 5.04 (d, J = 3.9 Hz, 1H, OH), 4.92 (ddd, J = 8.3, 4.1, 3.9 Hz,
1H, CH), 2.82 (ddd, J = 13.9, 4.1, 0.9 Hz, 1H, CH2), 2.72 (dd,
J = 13.9, 8.3, 0.8 Hz, 1H, CH2); 13C NMR (acetone-d6) d 168.6 (C),
146.6 (C), 144.2 (C), 142.7 (C), 142.1 (C), 141.0 (C), 130.4 (CH),
130.1 (CH), 129.2 (CH), 128.7 (CH), 128.1 (CH), 128.0 (CH), 127.0
(CH), 123.3 (CH), 122.7 (CH2), 199.5 (CH), 119.9 (CH), 74.5 (CH),
44.2 (CH2); HRMS (ESI+) m/z calcd for C23H21NO2+Na: 366.1465,
found 366.1447.
4.2. Experimental procedures
4.2.1. General procedure for the preparation of the chiral c-hydroxyam-
ides (Table 2). (S)-4-Hydroxy-2-methylene-N,4-diphenylbutanamide (6)
Under argon atmosphere, to the suspension of In(OTf)3
(13.2 mg, 0.0235 mmol) {predried at 120 °C for 1 h under reduced
pressure (ca. 1.0 Torr)} and MS 4Å (120 mg) {also predried at
180 °C for 3 h under reduced pressure (ca. 1.0 Torr)} in CH2Cl2
(0.7 mL) was added (S)-iPr-pybox 7a (14.2 mg, 0.0470 mmol) at
room temperature and stirred for 0.5 h. A solution of benzaldehyde
(5a) (30 mg, 0.282 mmol) in CH2Cl2 (0.2 mL) was added and stirred
for 1 h. The solution of 4a (106 mg, 0.235 mmol) in CH2Cl2 (0.3 mL)
was slowly added dropwise at the same temperature and stirred
for 16 h. The reaction was quenched by the addition of aqueous
NaHCO3 (5.0 mL), then CH2Cl2 was removed in vacuo. The mixture
was filtered through Celite and the resulting solution was ex-
tracted with ethyl acetate (30 mL). The combined organic extracts
were washed with brine (30 mL), dried over anhydrous Na2SO4,
and evaporated under reduced pressure. The residue was purified
by column chromatography (silica gel, hexane/EtOAc = 2:1) to give
4.2.1.4.
(S)-N-(3,5-Di-tert-butylphenyl)-4-hydroxy-2-methylene-4-
phenylbutanamide (11). M.p. 141.2–141.7 °C; ½a D20
ꢁ
ꢀ41.2 (c 1.76,
CHCl3); IR (KBr) 3277 (N–H), 2870 (O–H), 1599 (C@O) cmꢀ1
;
1H
NMR (CDCl3): d 8.16 (brs, 1H, NH), 7.41–7.20 (m, 8H, ArH), 5.81
(s, 1H, CH2), 5.34 (s, 1H, CH2), 4.92 (dt, J = 8.3, 3.3 Hz, 1H, CH),
4.33 (d, J = 3.3 Hz, 1H, OH), 2.81 (dd, J = 14.0, 3.3 Hz, 1H, CH2),
2.69 (dd, J = 14.0, 8.3 Hz, 1H, CH2), 1.32 (s, 18H, CH3); 13C NMR
(CDCl3) d 168.1 (C), 151.7 (C), 144.0 (C), 143.0 (C), 137.0 (C),
128.3 (CH), 127.4 (C), 125.8 (CH), 121.8 (CH2), 118.9 (CH), 114.8
(CH), 74.5 (CH), 43.1 (CH2), 34.9 (C), 31.4 (2CH3); HRMS (ESI+) m/
z calcd for C25H33NO2+Na: 402.2404, found 402.2433.
4.2.1.5. (S)-N-(4-tert-Butylphenyl)-4-hydroxy-2-methylene-4-phenyl-
butanamide (12). M.p. 164.0–165.0 °C; ½a D24
ꢀ55.9 (c 1.00, CHCl3);
ꢁ
IR (KBr) 2957 (N–H), 2868 (O–H), 1649 (C@O) cmꢀ1; 1H NMR (acet-
one-d6): d 9.46 (brs, 1H, NH), 7.67–7.65 (m, 2H, ArH), 7.43–7.18 (m,
6H, ArH), 7.21 (m, 1H, ArH), 5.86 (d, J = 0.9 Hz, 1H, CH2), 5.41 (d,
J = 0.9 Hz, 1H, CH2), 5.10 (brs, 1H, OH), 4.89 (dt, J = 8.3, 4.0 Hz,
1H, CH), 2.79 (ddd, J = 13.9, 4.0, 0.9 Hz, 1H, CH2), 2.68 (ddd,
J = 13.9, 8.3, 0.9 Hz, 1H, CH2), 1.30 (s, 9H, CH3); 13C NMR (acet-
one-d6): d 168.5 (C), 147.5 (C), 146.6 (C), 144.2 (C), 137.8 (C),
6 (60.0 mg, 96%) as a white solid. M.p. 101.1–102.0 °C; ½a D17
ꢀ46.7
ꢁ
(c 1.00, CHCl3); IR (KBr) 3279 (N–H), 2868 (O–H), 1647 (C@O)
;
cmꢀ1 1H NMR (CDCl3): d 8.65 (brs, 1H, NH), 7.54–7.08 (m, 10H,
ArH), 5.82 (s, 1H, CH2), 5.30 (s, 1H, CH2), 4.87 (ddd, J = 8.3, 3.4,

T. Suzuki et al. / Journal of Organometallic Chemistry 695 (2010) 128–136
133
129.2 (CH), 128.1 (CH), 127.0 (CH), 126.5 (CH), 122.4 (CH2), 120.8
(CH), 74.5 (CH), 44.3 (CH2), 35.2 (C), 32.0 (CH3); HRMS (ESI+) m/z
calcd for C21H25NO2+Na: 346.1778, found 346.1764.
NMR (CDCl3) d 167.9 (C), 159.0 (C), 147.7 (C), 143.0 (C), 136.1 (C),
135.0 (C), 127.0 (CH), 125.8 (CH), 122.0 (CH2), 120.0 (CH), 113.8
(CH), 74.3 (CH), 55.3 (CH3), 43.0 (CH2), 34.4 (C), 31.3 (CH3); HRMS
(ESI+) m/z calcd for C22H27NO3+Na: 376.1883, found 376.1871.
4.2.1.6. (S)-4-Hydroxy-N-(2-methoxyphenyl)-2-methylene-4-pheny-
lbutanamide (13). ½a D22
ꢁ
ꢀ2.07 (c 1.05, CHCl3); IR (NaCl) 3354 (N–
4.2.1.11. (S)-N-(4-tert-Butylphenyl)-4-(3-chlorophenyl)-4-hydroxy-
H), 3005 (O–H), 1649 (C@O), 1226 (C–O) cmꢀ1
;
1H NMR (CDCl3):
2-methylenebutanamide (18). M.p. 147.2–148.2 °C; ½a D24
ꢀ47.2 (c
ꢁ
d 8.54 (brs, 1H, NH), 8.34 (dd, J = 9.3, 1.4 Hz, 1H, ArH), 7.37–7.18
(m, 5H, ArH), 7.08–6.84 (m, 3H, ArH), 5.75 (s, 1H, CH2), 5.33 (s,
1H, CH2), 4.86 (ddd, J = 8.4, 3.7, 3.5 Hz, 1H, CH), 4.65 (d, J = 3.5 Hz,
1H, OH), 3.83 (s, 3H, CH3), 2.77 (dd, J = 14.1, 3.7 Hz, 1H, CH2),
2.65 (dd, J = 14.1, 8.4 Hz, 1H, CH2); 13C NMR (CDCl3): d 167.9 (C),
148.2 (C), 144.2 (C), 142.9 (C), 128.2 (CH), 127.2 (CH), 125.7 (CH),
124.2 (CH), 124.2 (CH), 121.5 (CH2), 121.0 (CH), 120.0 (CH), 110.0
(CH) 74.0 (CH), 55.7 (CH3), 43.2 (CH2). Anal. Calc. for C18H19NO3:
C, 72.71; H, 6.44; N, 4.71. Found: C, 73.04; H, 6.55; N, 4.98%.
1.00, CHCl3); IR (KBr) 3277 (N–H), 2959 (O–H), 1599 (C@O)
cmꢀ1 1H NMR (CDCl3): d 8.37 (brs, 1H, NH), 7.46–7.17 (m, 8H,
;
ArH), 5.85 (s, 1H, CH2), 5.30 (s, 1H, CH2), 5.09 (d, J = 3.3 Hz, 1H,
OH), 4.83 (dt, J = 8.3, 3.3 Hz, 1H, CH), 2.74 (dd, J = 14.1, 3.3 Hz,
1H, CH2), 2.59 (dd, J = 14.1, 8.3 Hz, 1H, CH2), 1.30 (s, 9H, CH3); 13C
NMR (CDCl3) d 168.2 (C), 148.0 (C), 146.2 (C), 142.4 (C), 134.7 (C),
134.2 (C), 129.6 (CH), 127.5 (CH), 125.94 (CH), 125.88 (CH), 123.9
(CH), 122.2 (CH2), 120.1 (CH), 73.8 (CH), 43.1 (CH2), 34.4 (C), 31.3
(CH3); HRMS (ESI+) m/z calcd for C21H24ClNO2+Na: 380.1388, found
380.1407.
4.2.1.7. (S)-4-Hydroxy-N-(4-methoxyphenyl)-2-methylene-4-phenyl-
butanamide (14). M.p. 121.6–122.2 °C; ½a D23
ꢁ
ꢀ0.06 (c 2.03, CHCl3);
4.2.1.12.
(S)-N-(4-tert-Butylphenyl)-4-hydroxy-2-methylene-4-(4-
IR (KBr) 3568 (N–H), 3279 (O–H), 1603 (C@O), 1250 (C–O) cmꢀ1
;
nitrophenyl)butanamide (19). M.p. 161.6–162.5 °C; ½a D24
ꢀ58.2 (c
ꢁ
1H NMR (CDCl3): d 8.40 (brs, 1H, NH), 7.43 (d, J = 9.0 Hz, 2H,
ArH), 7.36–7.23 (m, 5H, ArH), 6.85 (d, J = 9.0 Hz, 2H, ArH), 5.80 (s,
1H, CH2), 5.31 (s, 1H, CH2), 4.88 (dt, J = 8.3, 3.1 Hz, 1H, CH), 4.56
(d, J = 3.1 Hz, 1H, OH), 3.78 (s, 3H, CH3), 2.76 (dd, J = 14.1, 3.1 Hz,
1H, CH2), 2.65 (dd, J = 14.1, 8.3 Hz, 1H, CH2); 13C NMR (CDCl3) d
168.0 (C), 156.6 (C), 143.9 (C), 142.6 (C), 130.7 (C), 128.3 (CH),
127.4 (CH), 125.6 (CH), 122.3 (CH2), 122.0 (CH), 114.1 (CH), 74.7
(CH), 55.4 (CH3), 43.0 (CH2); HRMS (ESI+) m/z calcd for C18H19NO3+-
Na: 320.1257, found 320.1234.
1.00, CHCl3); IR (KBr) 2959 (N–H), 2868 (O–H), 1597 (C@O)
cmꢀ1
;
1H NMR (acetone-d6): d 9.36 (brs, 1H, NH), 8.18 (d,
J = 8.8 Hz, 2H, ArH), 7.69 (d, J = 8.8 Hz, 2H, ArH), 7.63 (d,
J = 8.8 Hz, 2H, ArH), 7.35 (d, J = 8.8 Hz, 2H, ArH), 5.87 (s, 1H, CH2),
5.46 (d, J = 4.0 Hz, 1H, OH), 5.33 (s, 1H, CH2), 5.08 (ddd, J = 7.9,
4.2, 4.0 Hz, 1H, CH), 2.86 (dd, J = 13.7, 4.2 Hz, 1H, CH2), 2.73 (dd,
J = 13.7, 7.9 Hz, 1H, CH2), 1.30 (s, 9H, CH3); 13C NMR (acetone-d6)
d 168.7 (C), 154.2 (C), 148.3 (C), 147.7 (C), 143.4 (C), 137.7 (C),
128.2 (CH), 126.6 (CH), 124.3 (CH), 122.7 (CH2), 121.0 (CH), 73.7
(CH), 44.0 (CH2), 35.2 (C), 32.0 (CH3); HRMS (ESI+) m/z calcd for
C21H24N2O4+Na: 391.1628, found 391.1647.
4.2.1.8. (R)-N-(4-tert-Butylphenyl)-4-hydroxy-6-methyl-2-methyle-
neheptanamide (15). M.p. 107.2–107.7 °C;
½
a 2D4
ꢁ
+3.62 (c 1.00,
CHCl3); IR (KBr) 3267 (N–H), 2957 (O–H), 1647 (C@O) cmꢀ1
;
1H
4.2.1.13.
nyl)-2-methylenebutanamide (20). M.p. 189.9–190.8 °C;
ꢀ38.0 (c 1.00, CHCl3); IR (KBr) 3184 (N–H), 2962 (O–H), 1600
(C@O) cmꢀ1 1H NMR (CDCl3): d 8.35 (brs, 1H, NH), 7.46 (d,
(S)-N-(4-tert-Butylphenyl)-4-hydroxy-4-(4-isopropylphe-
NMR (CDCl3): d 7.46 (d, J = 8.6 Hz, 2H, ArH), 7.30 (d, J = 8.6 Hz,
2H, ArH), 5.89 (s, 1H, CH2), 5.41 (s, 1H, CH2), 3.89–3.82 (m, 1H,
CH), 3.73 (brs, 1H, OH), 2.57 (dd, J = 14.1, 2.6 Hz, 1H, CH2), 2.35
(dd, J = 14.1, 8.3 Hz, 1H, CH2), 1.84–1.71 (m, 1H, CH), 1.50–1.41
(m, 1H, CH2), 1.30–1.21 (m, 1H, CH2), 1.29 (s, 9H, CH3), 0.92 (d,
J = 6.6 Hz, 3H, CH3), 0.90 (d, J = 6.6 Hz, 3H, CH3); 13C NMR (CDCl3)
d 167.8 (C), 147.3 (C), 143.4 (C), 135.3 (C), 125.7 (CH), 122.2
(CH2), 119.9 (CH), 70.1 (CH), 46.5 (CH2), 41.0 (CH2), 34.3 (C), 31.3
(CH3), 24.6 (CH), 23.2 (CH3), 22.1 (CH3); HRMS (ESI+) m/z calcd
for C19H29NO2+Na: 326.2091, found 326.2069.
½ ꢁ
a 2D3
;
J = 8.8 Hz, 2H, ArH), 7.34 (d, J = 8.8 Hz, 2H, ArH), 7.29 (d,
J = 8.2 Hz, 2H, ArH), 7.19 (d, J = 8.2 Hz, 2H, ArH), 5.84 (s, 1H, CH2),
5.37 (s, 1H, CH2), 4.87 (ddd, J = 8.3, 3.5, 3.1 Hz, 1H, CH), 3.94 (d,
J = 3.1 Hz, 1H, OH), 2.90 (sept, J = 7.0 Hz, 1H, CH), 2.78 (dd,
J = 14.3, 3.5 Hz, 1H, CH2), 2.69 (dd, J = 14.3, 8.3 Hz, 1H, CH2), 1.30
(s, 9H, CH3), 1.23 (d, J = 7.0 Hz, 6H, 2CH3); 13C NMR (CDCl3) d
167.8 (C), 148.3 (C), 147.5 (C), 143.0 (C), 141.3 (C), 135.1 (C),
126.4 (CH), 125.8 (CH), 125.7 (CH), 122.2 (CH2), 119.9 (CH), 74.7
(CH), 42.9 (CH2), 34.4 (C), 33.8 (CH), 31.3 (CH3), 23.9 (CH3). Anal.
Calc. for C24H31NO2: C, 78.86; H, 8.55; N, 3.83; Found: C, 79.12;
H, 8.64; N, 3.87%.
4.2.1.9. (S)-N-(4-tert-Butylphenyl)-4-hydroxy-5,5-dimethyl-2-methy-
lenehexanamide (16). M.p. 155.2–156.6 °C; ½a D20
ꢁ
+3.51 (c 0.41,
CHCl3); IR (KBr) 3568 (N–H), 2957 (O–H), 1597 (C@O) cmꢀ1
;
1H
NMR (CDCl3): d 8.39 (brs, 1H, NH), 7.47 (d, J = 6.7 Hz, 2H, ArH),
7.34 (d, J = 6.7 Hz, 2H, ArH), 5.88 (s, 1H, CH2), 5.46 (s, 1H, CH2),
3.39 (ddd, J = 10.2, 4.1, 2.0 Hz, 1H, CH), 3.06 (d, J = 4.1 Hz, 1H,
OH), 2.61 (dd, J = 13.9, 2.0 Hz, 1H, CH2), 2.29 (dd, J = 13.9, 10.2 Hz,
1H, CH2), 1.30 (s, 9H, CH3), 0.96 (s, 9H, CH3); 13C NMR (CDCl3): d
167.8 (C), 147.4 (C), 144.8 (C), 135.2 (C), 125.8 (CH), 121.2 (CH2),
119.8 (CH), 81.0 (CH), 35.3 (CH2), 35.2 (C), 34.4 (C), 31.3 (CH3),
25.5 (CH3). Anal. Calc. for C19H29NO2: C, 75.20; H, 9.63; N, 4.62.
Found: C, 75.13; H, 9.24; N, 4.57%.
4.2.1.14. (S)-N,4-Bis(4-tert-butylphenyl)-4-hydroxy-2-methylenebu-
tanamide (21). M.p. 199.7–201.1 °C; ½a D23
ꢀ34.1 (c 1.00, CHCl3);
ꢁ
IR (KBr) 2959 (N–H), 2866 (O–H), 1599 (C@O) cmꢀ1; 1H NMR (acet-
one-d6): d 9.40 (brs, 1H, NH), 7.63 (d, J = 8.8 Hz, 2H, ArH), 7.36–7.35
(m, 6H, ArH), 5.87 (s, 1H, CH2), 5.45 (s, 1H, CH2), 4.92 (d, J = 3.9 Hz,
1H, OH), 4.85 (ddd, J = 8.4, 4.1, 3.9 Hz, 1H, CH), 2.78 (dd, J = 13.7,
4.1 Hz, 1H, CH2), 2.67 (dd, J = 13.7, 8.4 Hz, 1H, CH2), 1.30 (s, 9H,
CH3), 1.28 (s, 9H, CH3); 13C NMR (acetone-d6) d 168.6 (C), 150.8
(C), 147.5 (C), 144.6 (C), 143.7 (C), 138.0 (C), 126.9 (CH), 126.6
(CH), 126.1 (CH), 122.2 (CH2), 120.8 (CH), 74.7 (CH), 44.3 (CH2),
35.3 (C), 35.2 (C), 32.1 (2CH3). Anal. Calc. for C25H33NO: C, 79.11;
H, 8.76; N, 3.69; Found: C, 79.34; H, 9.12; N, 3.81%.
4.2.1.10. (S)-N-(4-tert-Butylphenyl)-4-hydroxy-4-(4-methoxyphenyl)-
2-methylenebutanamide (17). M.p. 137.0–138.0 °C; ½a D23
ꢀ32.1 (c
ꢁ
1.00, CHCl3); IR (KBr) 3568 (N–H), 2964 (O–H), 1655 (C@O), 1248
(C–O) cmꢀ1 1H NMR (CDCl3): d 8.17 (brs, 1H, NH), 7.46 (d,
;
J = 8.8 Hz, 2H, ArH), 7.36 (d, J = 8.8 Hz, 2H, ArH), 7.30 (d,
J = 8.8 Hz, 2H, ArH), 6.87 (d, J = 8.8 Hz, 2H, ArH), 5.83 (s, 1H, CH2),
5.36 (s, 1H, CH2), 4.89 (dt, J = 8.1, 3.0 Hz, 1H, CH), 3.85 (d,
J = 3.0 Hz, 1H, OH), 3.79 (s, 3H, CH3), 2.79 (dd, J = 14.1, 3.0 Hz, 1H,
CH2), 2.70 (dd, J = 14.1, 8.1 Hz, 1H, CH2), 1.31 (s, 9H, CH3); 13C
4.2.1.15. (S)-N-(4-tert-Butylphenyl)-4-hydroxy-2-methylene-4-(naph-
thalen-1-yl)butanamide (22). M.p. 155.6–156.6 °C; ½a D24
ꢀ94.2 (c
ꢁ
1.00, CHCl3); IR (KBr) 3568 (N–H), 2961 (O–H), 1597 (C@O)
cmꢀ1
;
1H NMR (CD3OD): d 8.24 (d, J = 8.3 Hz, 1H, NH), 7.87–7.33
(m, 11H, ArH), 5.85 (s, 1H, CH2), 5.68 (dd, J = 8.7, 3.7 Hz, 1H, CH),

134
T. Suzuki et al. / Journal of Organometallic Chemistry 695 (2010) 128–136
5.45 (s, 1H, CH2), 3.07 (dd, J = 14.2, 8.7 Hz, 1H, CH2), 2.74 (dd,
J = 14.2, 3.7 Hz, 1H, CH2), 1.32 (s, 9H, CH3); 13C NMR (CD3OD) d
169.9 (C), 148.6 (C), 144.0 (C), 141.6 (C), 137.0 (C), 135.3 (C),
131.7 (C), 129.8 (CH), 128.8 (CH), 127.0 (CH), 126.7 (CH), 126.6
(CH), 126.5 (CH) 124.3 (CH), 123.9 (CH), 122.7 (CH2), 121.8 (CH),
70.8 (CH), 43.4 (CH2), 35.2 (C), 31.8 (CH3). Anal. Calc. for
C25H27NO2: C, 80.40; H, 7.29; N, 3.75. Found: C, 80.66; H, 7.35; N,
3.80%.
4.2.2.3. (S)-5-(4-tert-Butylphenyl)-3-methylenedihydrofuran-2(3H)-
one (27). M.p. 79.1–80.4 °C; ½a D23
ꢁ
+16.5 (c 1.22, CHCl3); IR (KBr)
1766 (C@O), 1279 (C–O) cmꢀ1
;
1H NMR (CDCl3): d 7.41 (d,
J = 8.0 Hz, 2H, ArH), 7.25 (d, J = 8.0 Hz, 2H, ArH), 6.30 (s, 1H, CH2),
5.68 (s, 1H, CH2), 5.51 (t, J = 7.2 Hz, 1H, CH), 3.41–3.35 (m, 1H,
CH2), 2.98–2.88 (m, 1H, CH2), 1.32 (s, 9H, CH3); 13C NMR (CDCl3)
d 170.2 (C), 151.7 (C), 136.7 (C), 134.4 (C), 125.7 (CH), 125.2 (CH),
122.2 (CH2), 77.9 (CH), 36.1 (CH2), 34.6 (C), 31.2 (CH3). Anal. Calc.
for C15H18O2: C, 78.23; H, 7.88. Found: C, 78.53; H, 7.65%.
4.2.1.16. (S)-N-(4-tert-Butylphenyl)-4-hydroxy-2-methylene-4-(nap-
hthalen-2-yl)butanamide (23). M.p. 157.0–158.0 °C; ½a D25
ꢁ
ꢀ60.1 (c
4.2.2.4. (S)-3-Methylene-5-(naphthalen-1-yl)dihydrofuran-2(3H)-one
1.00, CHCl3); IR (KBr) 3568 (N–H), 3223 (O–H), 1655 (C@O)
(28). ½a 2D2
ꢀ75.0 (c 2.45, CHCl3); IR (NaCl) 1764 (C@O), 1281 (C–O)
ꢁ
cmꢀ1
;
1H NMR (acetone-d6): d 9.47 (brs, 1H, NH), 7.89–7.84 (m,
cmꢀ1; 1H NMR (CDCl3): d 7.87–7.81 (m, 3H, ArH), 7.58–7.43 (m, 4H,
ArH), 6.34 (t, J = 2.8 Hz, 1H, CH2), 6.25 (dd, J = 8.3, 5.7 Hz, 1H, CH),
5.66 (t, J = 2.5 Hz, 1H, CH2), 3.62 (ddt, J = 17.0, 8.3, 2.8 Hz, 1H,
CH2), 2.95 (ddt, J = 17.0, 5.7, 2.5 Hz, 1H, CH2); 13C NMR (CDCl3) d
170.3 (C), 135.6 (C), 133.8 (C), 133.7 (C), 129.3 (C), 129.2 (CH),
128.7 (CH), 126.6 (CH), 125.9 (CH), 125.4 (CH), 123.0 (CH2), 122.3
(CH). 121.7 (CH), 75.4 (CH), 35.8 (CH2). Anal. Calc for C15H12O2: C,
80.34; H, 5.39. Found: C, 80.45; H, 5.51%.
4H, ArH), 7.69–7.57 (m, 3H, ArH), 7.50–7.34 (m, 4H, ArH), 5.85
(d, J = 0.8 Hz, 1H, CH2), 5.43 (d, J = 0.6 Hz, 1H, CH2), 5.25 (d,
J = 3.9 Hz, 1H, OH), 5.08 (ddd, J = 8.2, 4.3, 3.9 Hz, 1H, CH), 2.90
(ddd, J = 13.9, 4.3, 0.8 Hz, 1H, CH2), 2.79 (ddd, J = 13.9, 8.2, 0.6 Hz,
1H, CH2), 1.30 (s, 9H, CH3); 13C NMR (acetone-d6): d 168.6 (C),
147.5 (C), 144.2 (C), 144.1 (C), 137.8 (C), 134.6 (C), 134.1 (C),
129.1 (CH), 128.9 (CH), 128.8 (CH), 127.1 (CH), 126.7 (CH), 126.5
(CH), 125.7 (CH), 125.5 (CH), 122.4 (CH2), 120.8 (CH), 74.6 (CH),
44.2 (CH2), 35.2 (C), 32.0 (CH3). Anal. Calc. for C25H27NO2: C,
80.40; H, 7.29; N, 3.75; Found: C, 80.53; H, 7.62; N, 3.92%.
4.2.2.5. (S)-3-Methylene-5-(naphthalen-2-yl)dihydrofuran-2(3H)-one
(29). M.p. 70.0–71.0 °C; ½a D23
ꢁ
+34.9 (c 1.23, CHCl3); IR (KBr) 1757
(C@O), 1273 (C–O) cmꢀ1
;
1H NMR (CDCl3): d 7.85–7.81 (m, 4H,
4.2.2. General procedure for the preparation of
a
-methylene-
c
-
ArH), 7.51–7.48 (m, 2H, ArH), 7.37 (dd, J = 8.4, 1.8 Hz, 1H, ArH),
6.33 (t, J = 2.7 Hz, 1H, CH2), 5.70 (t, J = 2.5 Hz, 1H, CH2), 5.66 (dd,
J = 8.0, 7.3 Hz, 1H, CH), 3.45 (ddt, J = 17.1, 8.0, 2.5 Hz, 1H, CH2),
2.97 (ddt, J = 17.1, 7.3, 2.7 Hz, 1H, CH2); 13C NMR (CDCl3) d 170.2
(C), 137.0 (C), 134.1 (C), 133.2 (C), 133.0 (C), 128.9 (CH), 128.0
(CH), 127.7 (CH), 126.6 (CH), 126.5 (CH), 124.5 (CH), 122.7 (CH2),
122.6 (CH), 76.6 (CH), 36.2 (CH2). Anal. Calc. for C15H12O2: C,
80.34; H, 5.39. Found: C, 80.03; H, 5.28%.
butyrolactones from -hydroxy amides (Scheme 3). (S)-3-Methylene-
c
5-phenyldihydrofuran-2(3H)-one (24)
To a solution of 12 (121 mg, 0.453 mmol) in 1,4-dioxane
(1.3 mL) was added 10% HCl (1.0 mL) and warmed up to 65 °C.
After the mixture was stirred for 2 h, cooled to room temperature,
quenched by the addition of water (5.0 mL) and extracted with
ethyl acetate (30 mL). The combined organic extracts were washed
with brine (30 mL), dried over anhydrous Na2SO4, and concen-
trated in vacuo. The residue was purified by column chromatogra-
phy (silica gel, hexane/EtOAc = 4:1) to give 24 (76.0 mg, 96%) as a
4.2.2.6. tert-Butyl phenyl{2-[(tributylstannyl)methyl]acryloyl}carba-
mate (30). To
a solution of 4a (150 mg, 0.333 mmol), Et3N
colorless oil. ½a D23
ꢁ
+12.7 (c 1.00, CHCl3); IR (NaCl) 1757 (C@O),
(51.0 mg, 0.500 mmol), Boc2O (80.0 mg, 0.366 mmol) and DMAP
(41.0 mg, 0.333 mmol) in CH2Cl2 (0.7 mL) was stirred for 35 h at
room temperature. The reaction mixutre was filtered through Ce-
lite, then CH2Cl2 was removed in vacuo. The residue was purified
by column chromatography (silica gel, hexane/EtOAc = 20/1) to
give 30 (180 mg, 98%) as a colorless oil. IR (NaCl) 2957 (C–H),
1279 (C–O) cmꢀ1
;
1H NMR (CDCl3): d 7.42 (m, 5H, ArH), 6.30 (t,
J = 2.7 Hz, 1H, CH2), 5.69 (t, J = 2.4 Hz, 1H, CH2), 5.52 (dd, J = 8.0,
3.6 Hz, 1H, CH), 3.40 (ddt, J = 16.8, 8.0, 2.4 Hz, 1H, CH2), 2.90 (ddt,
J = 16.8, 3.6, 2.4 Hz, 1H, CH2); 13C NMR (CDCl3) d 170.1 (C), 139.8
(C), 134.2 (C), 128.8 (CH), 128.5 (CH), 125.3 (CH), 122.4 (CH2),
77.9 (CH), 36.2 (CH2). Anal. Calc. for C11H10O2: C, 75.84; H, 5.79.
Found: C, 75.86; H, 6.07%.
1737 (C@O), 1689 (C@O), 1153 (C–O) cmꢀ1 1H NMR (CDCl3): d
;
7.40–7.12 (m, 5H, ArH), 5.31 (s, 1H, CH2), 5.14 (s, 1H, CH2), 1.96
(s, 3H, CH2), 1.55–1.23 (m, 12H, CH2), 1.45 (s, 9H, CH3), 1.00–0.78
(m, 15H, CH2 and CH3); 13C NMR (CDCl3): d 174.7, 153.5, 148.2,
138.9, 129.0, 127.42, 127.38, 112.9, 83.2, 29.0, 27.8, 27.3, 15.9,
13.7, 10.2; HRMS (ESI+) m/z calcd for C27H45NO3Sn+Na: 574.2314,
found 574.2278.
4.2.2.1. (R)-5-Isobutyl-3-methylenedihydrofuran-2(3H)-one (25).
.½a 2D1
ꢁ
+ 26.1 (c 0.96, EtOH); IR (NaCl) 1762 (C@O), 1274 (C–O)
;
cmꢀ1
1H NMR (CDCl3): d 6.22 (t, J = 2.8 Hz, 1H, CH2), 5.62 (t,
J = 2.5 Hz, 1H, CH2), 4.64–4.55 (m, 1H, CH), 3.07 (ddt, J = 16.9, 7.7,
2.5 Hz, 1H, CH2), 2.54 (ddt, J = 16.9, 6.2, 2.8 Hz, 1H, CH2), 1.92–
1.79 (m, 1H, CH), 1.69 (ddd, J = 14.0, 8.7, 6.2 Hz, 1H, CH2), 1.41
(ddd, J = 14.0, 8.1, 5.1 Hz, 1H, CH2), 0.97 (d, J = 6.6 Hz, 3H, CH3),
0.95 (d, J = 6.6 Hz, 3H, CH3); 13C NMR (CDCl3) d 170.4 (C), 134.7
(C), 121.9 (C), 76.1 (CH), 45.5 (CH2), 34.1 (CH2), 24.7 (CH), 22.9
(CH3), 22.1 (CH3). Anal. Calc. for C9H14O2: C, 70.10; H, 7.46. Found:
C, 69.77; H, 8.77%.
4.2.3. General procedure for the preparation of b-alkoxycarbonyl ally-
ltributylstannanes 31 and 32 (Scheme 4). Ethyl 2-[(tributylstannyl)-
methyl]acrylate (31)
To a solution of NaH (192 mg, 8.34 mmol) and ethanol (5.0 mL)
was added a solution of 30 (1.53 g, 2.78 mmol) in ethanol (3.3 mL)
at 0 °C and warmed up to room temperature. After stirred for 1 h,
the reaction was quenched by the addition of saturated aqueous
NH4Cl (5.0 mL) and the resulting solution was extracted with ethyl
acetate (30 mL). The combined organic extracts were washed with
brine (30 mL), dried over anhydrous Na2SO4, and concentrated in
vacuo. The residue was purified by column chromatography (silica
gel, hexane/EtOAc = 60:1) to give 31 (1.02 g, 92%) as a colorless oil.
4.2.2.2. (S)-5-(4-Isopropylphenyl)-3-methylenedihydrofuran-2(3H)-
one (26). ½a 2D3
ꢁ
+17.0 (c 1.46, CHCl3); IR (NaCl) 1767 (C@O), 1277
(C–O) cmꢀ1
;
1H NMR (CDCl3): d 7.26–7.25 (m, 4H, ArH), 6.30 (t,
J = 2.8 Hz, 1H, CH2), 5.68 (t, J = 2.5 Hz, 1H, CH2), 5.50 (dd, J = 7.7,
6.6 Hz, 1H, CH), 3.37 (ddt, J = 17.0, 7.7, 2.5 Hz, 1H, CH2), 2.95–
2.87 (m, 2H, CH and CH2), 1.25 (d, J = 7.0 Hz, 6H, CH3); 13C NMR
(CDCl3) d 170.2 (C), 149.4 (C), 137.1 (C), 134.4 (C), 126.9 (CH),
125.5 (CH), 122.2 (CH2), 78.0 (CH), 36.2 (CH2), 33.8 (CH), 23.9
(CH3). Anal. Calc. for C14H16O2: C, 77.75; H, 7.46. Found: C, 78.08;
H, 7.42%.
IR (NaCl) 2926 (C–H), 1713 (C@O), 1178 (C–O) cmꢀ1 1H NMR
;
(CDCl3): d 5.81 (s, 1H, CH2), 5.27 (s, 1H, CH2), 4.18 (q, J = 7.1 Hz,
2H, CH2), 1.97 (s, 2H, CH2), 1.59–1.23 (m, 12H, CH2), 1.30 (t,
J = 7.1 Hz, 3H, CH3), 0.97–0.75 (m, 15H, CH2 and CH3); 13C NMR
(CDCl3): d 167.8, 141.3, 118.4, 60.6, 29.0, 27.3, 14.9, 14.2, 13.7,

T. Suzuki et al. / Journal of Organometallic Chemistry 695 (2010) 128–136
135
9.7; HRMS (ESI+) m/z calcd for C18H36O2Sn+Na: 427.1629, found
matography (silica gel, hexane/EtOAc = 6:1) to give 24 (46.0 mg,
427.1679.
93%) as a colorless oil.
4.2.3.1. Methyl 2-[(tributylstannyl)methyl]acrylate (32). IR (NaCl)
Acknowledgements
2926 (C–H), 1720 (C@O), 1169 (C–O) cmꢀ1 1H NMR (CDCl3): d
;
5.81 (s, 1H, CH2), 5.29 (s, 1H, CH2), 3.73 (s, 3H, CH3), 1.97 (s, 2H,
CH2), 1.56–1.23 (m, 12H, CH2), 0.96–0.77 (m, 15H, CH2 and CH3);
13C NMR (CDCl3): d 168.2, 141.0, 118.7, 51.7, 29.0, 27.3, 15.0,
13.7, 9.7; HRMS (ESI+) m/z calcd for C17H34O2Sn+Na: 413.1473,
found 413.1519.
This work was supported in part by a Grant-in-Aid for Scientific
Research from Japan Society for the Promotion of Science. We ac-
knowledge Nanotechnology Network Project (Kyushu-area Nano-
technology Network) of the Ministry of Education, Culture,
Sports, Science and Technology (MEXT), Japan.
4.2.3.2. General procedure for the preparation of b-alkoxycarbonyl
allyltributylstannanes 33–35 (Scheme 4); isopropyl 2-[(tributylstan-
nyl)methyl]acrylate (33). To a solution of NaH (66.0 mg, 2.725
mmol) and 2-propanol (164 mg, 2.725 mmol) in THF (1.0 mL)
was added a solution of 30 (500 mg, 0.908 mmol) in THF (1.0 mL)
at 0 °C and warmed up to room temperature. After stirred for
30 min, the reaction was quenched by the addition of saturated
aqueous NH4Cl (5.0 mL) and the resulting solution was extracted
with ethyl acetate (30 mL). The combined organic extracts were
washed with brine (30 mL), dried over anhydrous Na2SO4, and con-
centrated in vacuo. The residue was purified by column chromato-
graphy (silica gel, hexane/EtOAc = 50:1) to give 33 (257 mg, 68%)
as a colorless oil. IR (NaCl) 2926 (C–H), 1709 (C@O), 1182 (C–O)
References
[1] (a) For the general reviews, see: H. Yamamoto, M. Wadamoto, Chem. Asian J. 2
(2007) 692;
(b) E.J. Thomas, Chem. Rec. 7 (2007) 115;
(c) J.W.J. Kennedy, D.G. Hall, Angew. Chem., Int. Ed. 42 (2003) 4732;
(d) S.E. Denmark, J. Fu, Chem. Rev. 103 (2003) 2763;
(e) A. Yanagisawa, in: E.N. Jacobsen, A. Pfaltz, H. Yamamoto (Eds.),
Comprehensive Asymmetric Catalysis, Vols. IꢀIII, vol. 2, Springer, New York,
1999, pp. 965–979;
(f) Y. Yamamoto, N. Asao, Chem. Rev. 93 (1993) 2207. and references cited
therein.
[2] (a) For recent examples on the asymmetric allylation of aldehydes with
allylsilanes or allylstannanes, see: A. Kadlcikova, R. Hrdina, I. Valterova, M.
Kotora, Adv. Synth. Catal. 351 (2009) 1279;
(b) L.C. Dias, T. Augusto, C.C. Perez, L.J. Steil, J. Braz. Chem. Soc. 20 (2009) 802;
(c) A.V. Malkov, P. Ramirez-Lopez, L. Biedermannova, L. Rulisek, L. Dufkova, M.
Kotora, F. Zhu, P. Kocovsky, J. Am. Chem. Soc. 130 (2008) 5341;
(d) R.K. Sharma, A.G. Samuelson, Tetrahedron: Asymmetr. 18 (2007) 2387;
(e) L.-Y. Liu, J. Sun, N. Liu, W.-X. Chang, J. Li, Tetrahedron: Asymmetr. 18 (2007)
710;
(f) G. Chelucci, N. Belmonte, M. Benaglia, L. Pignataro, Tetrahedron Lett. 48
(2007) 4037;
(g) S. Kotani, S. Hashimoto, M. Nakajima, Tetrahedron 63 (2007) 3122;
(h) K. Takeuchi, T. Takeda, T. Fujimoto, I. Yamamoto, Tetrahedron 63 (2007)
5319;
(i) S.E. Denmark, J. Fu, M.J. Lawler, J. Org. Chem. 71 (2006) 1523;
(j) M. Chen, Y. Zheng, S. Fan, G. Gao, L. Yang, L. Tian, Y. Du, F. Tang, W. Hua,
Synth. Commun. 36 (2006) 1063;
(k) Q. Chai, C. Song, Z. Sun, Y. Ma, C. Ma, Y. Dai, M.B. Andrus, Tetrahedron Lett.
47 (2006) 8611;
(l) P. Kwiatkowski, W. Chaladaj, J. Jurczak, Tetrahedron 62 (2006) 5116;
(m) G.-L. Li, G. Zhao, J. Org. Chem. 70 (2005) 4272;
(n) M. Chen, S. Guo, Y. Zheng, L. Chen, F. Tang, W. Hua, Heterocycl. Commun.
11 (2005) 285;
cmꢀ1 1H NMR (CDCl3): d 5.78 (s, 1H, CH2), 5.26 (s, 1H, CH2), 5.04
;
(sept, J = 6.2 Hz, 1H, CH), 1.96 (s, 2H, CH2), 1.59–1.20 (m, 12H,
CH2), 1.27 (d, J = 6.2 Hz, 6H, CH3), 0.97–0.75 (m, 15H, CH2 and
CH3); 13C NMR (CDCl3): d 167.3, 141.7, 118.0, 67.8, 29.0, 27.3,
21.8, 14.8, 13.6, 9.7. Anal. Calc. for C19H38O2Sn: C, 54.70; H, 9.18.
Found: C, 54.61; H, 8.81%.
4.2.3.3. Benzyl 2-[(tributylstannyl)methyl]acrylate (34). IR (NaCl)
2926 (C–H), 1717 (C@O), 1165 (C–O) cmꢀ1 1H NMR (CDCl3): d
;
7.28–7.20 (m, 5H, ArH), 5.79 (s, 1H, CH2), 5.23 (s, 1H, CH2), 5.08
(s, 2H, CH2), 1.91 (s, 2H, CH2), 1.47–1.12 (m, 12H, CH2), 0.81–0.71
(m, 15H, CH2 and CH3); 13C NMR (CDCl3): d 167.8, 141.1, 136.1,
128.4, 128.1, 128.0, 118.9, 66.4, 28.9, 27.3, 14.9, 13.7, 9.7; HRMS
(ESI+) m/z calcd for C23H38O2Sn+Na: 489.1786, found 489.1835.
(o) Y.-C. Teo, E.-L. Goh, T.-P. Loh, Tetrahedron Lett. 46 (2005) 6209;
(p) P. Kwiatkowski, W. Chaladaj, J. Jurczak, Synlett (2005) 2301;
(q) P. Kwiatkowski, J. Jurczak, Synlett (2005) 227;
(r) A.V. Malkov, M. Bell, F. Castelluzzo, P. Kocovsky, Org. Lett. 7 (2005) 3219;
(s) G. Xia, K. Shibatomi, H. Yamamoto, Synlett (2004) 2437;
(t) A. Kina, T. Shimada, T. Hayashi, Adv. Synth. Catal. 346 (2004) 1169;
(u) A. Yanagisawa, Y. Nakamura, T. Arai, Tetrahedron: Asymmetr. 15 (2004)
1909;
4.2.3.4. Phenyl 2-[(tributylstannyl)methyl]acrylate (35). IR (NaCl)
2926 (C–H), 1732 (C@O), 1200 (C–O) cmꢀ1 1H NMR (CDCl3): d
;
7.42–7.35 (m, 2H, ArH), 7.25–7.19 (m, 1H, ArH), 7.11–7.06 (m,
2H, ArH), 6.06 (s, 1H, CH2), 5.48 (s, 1H, CH2), 2.07 (s, 2H, CH2),
1.60–1.23 (m, 12H, CH2), 1.01–0.79 (m, 15H, CH2 and CH3); 13C
NMR (CDCl3): d 166.3, 151.1, 140.8, 129.4, 125.6, 121.6, 120.3,
29.0, 27.3, 15.0, 13.7, 9.8; HRMS (ESI+) m/z calcd for C22H36O2S-
n+Na: 475.1629, found 475.1650.
(v) M. Nakajima, S. Kotani, T. Ishizuka, S. Hashimoto, Tetrahedron Lett. 46
(2004) 157. and references cited therein.
[3] (a) W.R. Roush, in: B.M. Trost, I. Fleming, C.H. Heathcock (Eds.),
Comprehensive Organic Synthesis, vol. 2, Pergamon, Oxford, UK, 1991, p. 1;
(b) Y. Yamamoto, N. Asao, Chem. Rev. 93 (1993) 2207;
(c) J.A. Marshall, Chem. Rev. 96 (1996) 31.
[4] (a) T. Suzuki, T. Sengoku, M. Takahashi, H. Yoda, Tetrahedron Lett. 49 (2008)
4701;
4.2.4. General procedure for the preparation of chiral a-methylene-c-
butyrolactone 24 from b-alkoxycarbonyl allyltributylstannanes (Table
4, entry 4)
(b) Y. Nishigaichi, K. Tamura, N. Ueda, H. Iwamoto, A. Takuwa, Tetrahedron
Lett. 49 (2008) 2124;
(c) K. Tanaka, H. Yoda, Y. Isobe, A. Kaji, Tetrahedron Lett. 26 (1985) 1337;
(d) K. Tanaka, H. Yoda, Y. Isobe, A. Kaji, J. Org. Chem. 51 (1986) 1856.
Under argon atmosphere, to the suspension of InCl3 (9.4 mg,
0.0425 mmol) {predried at 140 °C for 2 h under reduced pressure
(ca. 1.0 Torr)} and MS 4Å (120 mg) {also predried at 180 °C for
3 h under reduced pressure (ca. 1.0 Torr)} in CH2Cl2 (0.9 mL) was
added (S)-BINOL 7c (16.2 mg, 0.0566 mmol) at room temperature
and stirred for 2 h. A solution of benzaldehyde (5a) (36.0 mg,
0.340 mmol) in CH2Cl2 (0.2 mL) was added and stirred for 1 h.
Then, 31 (114 mg, 0.283 mmol) in CH2Cl2 (0.2 mL) was slowly
added dropwise at the same temperature and stirred for 7 days.
The reaction was quenched by the addition of aqueous NaHCO3
(5.0 mL), then CH2Cl2 was removed in vacuo. The mixture was fil-
tered through Celite and the resulting solution was extracted with
ethyl acetate (30 mL). The combined organic extracts were washed
with brine (30 mL), dried over anhydrous Na2SO4, and evaporated
under reduced pressure. The residue was purified by column chro-
[5] (a) For reviews on
a-methylene-c-lactones, see: R. Bandichhor, B. Nosse, O.
Reiser, Top. Curr. Chem. 243 (2005) 43;
(b) T. Janecki, E. Blaszczyk, K. Studzian, A. Janecka, U. Krajewska, M.J.
Rosalski, Med. Chem. 48 (2005) 3516;
(c) H.M. Hoffmann, J. Rabe, Angew. Chem., Int. Ed. Engl. 24 (1985) 94;
(d) . For recent examples, see:C. Isabelle, Z. Françoise, L. Jacques, V. Jean,
Tetrahedron 64 (2008) 2441;
(e) P.V. Ramachandran, D. Pratihar, Org. Lett. 9 (2007) 2087;
(f) A.-C. Le Lamer, N. Gouault, M. David, J. Boustie, P. Uriac, J. Comb. Chem. 8
(2006) 643;
(g) A. Szumny, C. Wawrzenczyk, Synlett (2006) 1523;
(h) C.S. Consorti, G. Ebeling, J. Dupont, Tetrahedron Lett. 43 (2002) 753;
(i) S. Yamauchi, N. Yamamoto, Y. Kinoshita, Biosci. Biotechnol. Biochem. 64
(2000) 2209;
(j) W. Adam, P. Groer, C.R. Saha-Moller, Tetrahedron: Asymmetr. 11 (2000)
2239;

136
T. Suzuki et al. / Journal of Organometallic Chemistry 695 (2010) 128–136
(k) R. Csuk, C. Schröder, S. Hutter, K. Mohr, Tetrahedron: Asymmetr. 8 (1997)
1411. and references cited therein.
[6] (a) Eantioselective allylation in the presence of indium(III) triflate-pybox
catalyst, see: J. Lu, S.-J. Ji, Y.-C. Teo, T.-P. Loh, Org. Lett. 7 (2005) 159;
(b) J. Lu, M.-L. Hong, S.-J. Ji, T.-P. Loh, Chem. Commun. (2005) 1010;
(c) J. Lu, S.-J. Ji, T.-P. Loh, Chem. Commun. (2005) 2345;
[8] (a) Enantioselective allylation in the presence of indium(III)-BINOL catalyst,
see: Y.-C. Teo, E.-L. Goh, T.-P. Loh, Tetrahedron Lett. 46 (2005) 6209;
(b) Y.-C. Teo, K.-T. Tan, T.-P. Loh, Chem. Commun. (2005) 1318. and references
cited therein.
[9] The absolute configurations of the stereogenic center of 6 and 15 were easily
determined to be S and R after derivation to the corresponding
lactones 24 and 25, respectively [4d,5k].
a-methylene-c-
(d) J. Lu, M.-L. Hong, S.-J. Ji, Y.-C. Teo, T.-P. Loh, Chem. Commun. (2005) 4217;
(e) Y.-C. Teo, E.-L. Goh, T.-P. Loh, Tetrahedron Lett. 46 (2005) 4573;
(f) J. Lu, S.-J. Ji, Y.-C. Teo, T.-P. Loh, Tetrahedron Lett. 46 (2005) 7435. and
references cited therein.
[10] The same allylation reaction of benzaldehyde (5a) with 30 containing the
electron-withdrawing Boc group on the nitrogen atom afforded the
corresponding adduct in satisfactory chemical yield (81%), albeit in low
enantiomeric excess (12% ee).
[7] The reactions did not proceed under any conditions with a catalytic amount of
metals such as La(OTf)3, Sm(OTf)3, Yb(OTf)3 and InCl3. The use of Sc(OTf)3
resulted in giving the desired
c-hydroxy amide 6 in low chemical yield and
enantiomeric excess (21%, 3.8% ee).