Ir-catalyzed allylic amination/ring-closing metathesis: A new route to enantioselective synthesis of cyclic β-amino alcohol derivatives

Article abstract of DOI:10.1021/jo070998h

(Chemical Equation Presented) Ir-catalyzed allylic aminations of (E)-4-benzyloxy-2-butenyl methyl carbonate with benzylamine using Feringa's (S_a,S_c,S_c)- phosphoramidite as a chiral ligand afforded linear-aminated achiral p

Full text of DOI:10.1021/jo070998h

analogues. Therefore, the development of more general and
flexible enantioselective synthetic methods for cyclic â-amino
alcohol derivatives represents a desirable goal.
Ir-Catalyzed Allylic Amination/Ring-Closing
Metathesis: A New Route to Enantioselective
Synthesis of Cyclic â-Amino Alcohol Derivatives
Over the past few years, Ir-catalyzed asymmetric allylic
substitutions of an achiral or racemic allylic ester or carbonate
have been extensively studied and utilized to generate new
stereogenic carbon centers bonded to carbon,5 nitrogen,6 and
oxygen atoms.7 In particular, regio- and enantioselective allylic
aminations and etherifications of terminal allylic electrophiles
using the Ir complex of chiral phosphoramidite have proven to
be an extremely useful method for the synthesis of chiral N-
and O-heterocyclic compounds such as 2-vinylazacycloalkanes,6d
2,5-divinylpyrrolidines,6h,j disubstituted dehydropyrrolidines,6k
dihydropyrans, and dihydrofurans.7b It has also been reported
that the asymmetric Ir-catalyzed allylic alkylation of O-protected
allylic carbonates 1 (n ) 1)8 or stereospecific Rh-catalyzed
allylic amination of enantiomerically pure allylic carbonates,9
Jun Hee Lee,† Seunghoon Shin,*,‡ Jahyo Kang,*,† and
Sang-gi Lee*,§
DiVision of Nano Science (BK21)/Department of Chemistry,
Ewha Womans UniVersity, 11-1, Daehyun-Dong,
Seodaemun-Gu, 120-750 Seoul, Korea, Department of
Chemistry, Sogang UniVersity, Seoul, Korea, and Department of
Chemistry (BK21), Hanyang UniVersity, Seoul, Korea
sanggi@ewha.ac.kr
ReceiVed May 15, 2007
(1) (a) Lovell, P. J.; Bromidge, S. M.; Dabbs, S.; Duckworth, D. M.;
Forbes, I. T.; Jennings, A. J.; King, F. D.; Middlemiss, D. N.; Rahman, S.
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Chem. 2002, 67, 6456. (e) Deng, X.; Mani, N. S. Tetrahedron: Asymmetry
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Orland, M. D. Org. Lett. 2005, 7, 3383.
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Katritzky, A. R.; Zhang, S.; Fang, Y. Org. Lett. 2000, 2, 3789. (c) Katritzky,
A. R.; Zhang, S.; Hussein, A. H. M.; Fang, Y.; Steel, P. J. J. Org. Chem.
2001, 66, 5606. (d) Kowalski, C. J.; Reddy, R. E. J. Org. Chem. 1992, 57,
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4849.
(3) (a) EnantioselectiVe Synthesis of â-Amino Acids; Juaristi, E., Ed.;
Wiley-VCH: New York, 1997. (b) Sewald, N. Angew. Chem., Int. Ed. 2003,
42, 5794. (c) Chippindale, A. M.; Davies, S. G.; Iwamoto, K.; Parkin, R.
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2003, 59, 3253. (d) Perlmutter, P.; Rose, M.; Vounatsos, F. Eur. J. Org.
Chem. 2003, 756. (e) Lesma, G.; Danieli, B.; Sacchetti, A.; Silvani, A. J.
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B.; Garc´ıa-Yebra, C.; Rominger, F.; Helmchen, G. Eur. J. Inorg. Chem.
2002, 2569. (c) Lipowsky, G.; Miller, N.; Helmchen, G. Angew. Chem.,
Int. Ed. 2004, 116, 4595. (d) Alexakis, A.; Polet, D. Org. Lett. 2004, 6,
3529.
(6) (a) Ohmura, T.; Hartwig, J. F. J. Am. Chem. Soc. 2002, 124, 15164.
(b) Kiener, C. A.; Shu, C.; Incarvito, C.; Hartwig, J. F. J. Am. Chem. Soc.
2003, 125, 14272. (c) Lipowsky, G.; Helmchen, G. Chem. Commun. 2004,
116. (d) Welter, C.; Koch, O.; Lipowsky, G.; Helmchen, G. Chem. Commun.
2004, 896. (e) Tissot-Croset, K.; Polet, D.; Alexakis, A. Angew. Chem.,
Int. Ed. 2004, 43, 2426. (f) Shu, C.; Leitner, A.; Hartwig, J. F. Angew.
Chem., Int. Ed. 2004, 43, 4797. (g) Leitner, A.; Shu, C.; Hartwig, J. F.
Org. Lett. 2005, 7, 1093. (h) Welter, C.; Dahnz, A.; Brunner, B.; Streiff,
S.; Du¨bon, P.; Helmchen, G. Org. Lett. 2005, 7, 1239. (i) Polet, D.; Alexakis,
A. Org. Lett. 2005, 7, 1621. (j) Weihofen, R.; Dahnz, A.; Tverskoy, O.;
Helmchen, G. Chem. Commun. 2005, 3541. (k) Weihofen, R.; Tverskoy,
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4794.
(8) Streiff, S.; Welter, C.; Schelwies, M; Lipowsky, G.; Miller, N.;
Helmchen, G. Chem. Commun. 2005, 2957.
Ir-catalyzed allylic aminations of (E)-4-benzyloxy-2-butenyl
methyl carbonate with benzylamine using Feringa’s (Sa,Sc,Sc)-
phosphoramidite as a chiral ligand afforded linear-aminated
achiral product N,O-dibenzyl-4-amino-2-buten-1-ol regiose-
lectively (linear/branched ) >99/1), whereas the (E)-5-
benzyloxy-2-pentenyl methyl carbonate showed completely
opposite regioselectivity (linear/branched ) >1/99) and
afforded the optically active (3R)-N,O-dibenzylated 3-amino-
1-penten-5-ol with very high enantioselectivity (96% ee),
which was used as a key intermediate for the effective
synthesis of various cyclic â-amino alcohol derivatives
through ring-closing metathesis in high yields.
Due to their ubiquity in biologically interesting natural and
synthetic compounds, the stereoselective synthesis of cyclic
â-amino alcohols, particularly 2-hydroxyethylpyrrolidines, has
become an increasingly important synthetic target.1 The most
commonly employed method is carboxylic acid reduction of
optically active cyclic â-amino acids, which are generally
prepared by the homologation of cyclic R-amino acids.2
However, although a number of interesting and synthetically
useful methods for optically active cyclic â-amino acids have
been developed,3,4 they are often specific to a particular ring
size (generally 5- and 6-membered rings) and/or stereochemical
motif. Hence, cyclic â-amino acid-based approaches include
limitations to their utility as general methods for synthesizing
optically active 2-hydroxyethyl pyrrolidine and its cyclic
† Sogang University.
‡ Hanyang University.
§ Ewha Womans University. (S.-g.L.) Phone: +82-2-3277-4505. Fax: +82-
(9) (a) Evans, P. A.; Robinson, J. E.; Nelson, J. D. J. Am. Chem. Soc.
1999, 121, 6761. (b) Evans, P. A.; Robinson, J. E. Org. Lett. 1999, 1, 1929.
2-3277-3419.
10.1021/jo070998h CCC: $37.00 © 2007 American Chemical Society
Published on Web 08/18/2007
J. Org. Chem. 2007, 72, 7443-7446
7443

TABLE 1. Ir-Catalyzed Allylic Amination of O-Protected
Hydroxyalkyl-Substituted Allylic Carbonates 1 with Benzylamine
Using Achiral P(OPh)3 and Chiral (Sa,Sc,Sc)-Phosphoramidite as
Ligandsa
SCHEME 1. Ir-Catalyzed Allylic Amination/Ring-Closing
Metathesis for Cyclic Amino Alcohol Derivatives
entry
1
ligand
2/3b
5:95
3:97
>99:1
2.5:1
yield (2 + 3)c (%) % ee (2)d
1
2
3
1a
P(OPh)3
40
32
1b P(OPh)3
1c
1c
1c
1a
P(OPh)3
(Sa,Sc,Sc)-L
(Sa,Sc,Sc)-L >99:1
(Sa,Sc,Sc)-L
89
59
94
42
27
racemic
77
96
4e
5f
6f
7f
in combination with ring-closing metathesis (RCM), afforded
carbocycles and dihydropyrroles, respectively. Surprisingly, no
report on the regio- and enantioselective Ir-catalyzed allylic
amination of O-protected hydroxyalkyl-substituted carbonates
such as 1 has been found in the literature. As shown in Scheme
1, we anticipated that the regio- and enantioselective Ir-catalyzed
allylic aminations of O-protected hydroxyalkyl-substituted allylic
carbonates 1 could provide a new route for the synthesis of
optically active N,O-protected allylamines 2. In particular,
3-amino-1-penten-5-ol (n ) 2 in 2), which is generally
synthesized by multistep synthesis starting from L-cysteine (or
after conversion into homoserine),10 was expected to be a key
intermediate for the synthesis of pyrrolidines 6 and pyrrolidi-
nones 7 (Scheme 1). Here, we report the Ir-catalyzed allylic
aminations of O-protected hydroxyalkyl-substituted allylic
carbonates 1 providing a new route for the N,O-dibenzylated
optically active 3-amino-1-penten-5-ol 2 (n ) 2), which has
been used as a key intermediate for the synthesis of various
cyclic â-amino alcohol derivatives through ring-closing me-
tathesis.
It has been generally known that Ir-catalyzed allylic substitu-
tions of the linear allylic carbonates proceed regiospecifically,
i.e., the substrates having (E)-geometry show much higher
selectivity for branched product than the (Z)-substrates.5b,11
Based on these observations, the regioselectivity of the (E)-4-
benzyloxy-2-butenyl methyl carbonate (1a)12 having (E)-
geometry was investigated first in an Ir-catalyzed (1 mol % of
[Ir(COD)Cl]2) allylic amination with benzylamine using achiral
P(OPh)3 (2 mol %) as a ligand at room temperature for 12 h.
Unfortunately, the linear-aminated product 3a was formed
regioselectively (2a/3a ) 4:96) in 40% yield (entry 1, Table
1), and most of the starting 1a remained unreacted. Changing
the benzyl protection group to the sterically bulky triisopropyl-
silyl (TIPS) group (1c)12 did not improve the regioselectivity
(2b/3b ) 3:97) and yield at all (entry 2, Table 1). There were
no signs for the formation of corresponding branched amines
2a and 2b from 1a and 1b, respectively, in the 1H NMR analysis.
>1:99
>1:99
1b (Sa,Sc,Sc)-L
a Reactions were carried out at room temperature using 1 mol % of Ir
catalyst ([Ir(COD)Cl]2 and 2 mol % of ligand in THF (0.5 M). b Ratio
determined by 1H NMR analysis of crude mixture. c Isolated yield.
d Determined by HPLC analysis using a chiral column (Daicel CHIRALCEL
OD-H). e Catalyst was activated in situ with DABCO (conditions A).
f Catalyst was pre-activated with n-propylamine (conditions B).
Fortunately, under the same reaction conditions, completely
opposite regioselectivity was observed from the one-carbon
elongated substrate 1c,12 and thus, only the branch-aminated
racemic 2c was formed in 89% yield (entry 3, Table 1).
Regioselective formation of the branched allylic amine 2c
suggests the possibility of asymmetric synthesis of optically
active 2c by Ir-catalyzed allylic amination of 1c. Thus, we next
carried out asymmetric allylic amination of the (E)-5-benzyloxy-
2-pentenyl methyl carbonate (1c)12 using Feringa’s (Sa,Sc,Sc)-
phosphoramidite ligand (L), which is known to be one of the
most effective chiral ligands for Ir-catalyzed allylic aminations.13
As pointed out by Helmchen5b,6h and Hartwig,6f,g it has been
found that the regio- and enantioselectivity were largely
dependent on the catalyst preparation. Initially, the [Ir(COD)-
Cl]2 (1 mol %) was activated in situ by using 10 mol % of
1,2-diazabicyclo[2.2.2]octane (DABCO) to form an activated
iridacyclic complex (conditions A), which is known to be an
excellent active catalyst for aminations.6b,f However, a mixture
of branched 2c (42%) and linear amine 3c (17%) was formed
with low regioselectivity (ca. 2c/3c ) 2.5:1) and a moderate
enantioselectivity of 2c (77% ee) (entry 4, Table 1). Gratifyingly,
when the catalyst was preactivated with n-propylamine,6g
extremely high regio- and enantioselectivity were observed. The
preactivated catalyst was prepared by stirring a solution of [Ir-
(COD)Cl]2 (1 mol %) and (Sa,Sc,Sc)-L (2 mol %) in THF/n-
propylamine (v/v, 1:1) at 50 °C for 30 min (conditions B). After
evaporation of all of the volatiles, the remaining activated
catalyst was used directly for allylic aminations. Thus, the allylic
carbonate 1c and benzylamine were added to a solution of the
preactivated Ir catalyst (2 mol %) in THF (1.0 M), and the
reaction mixture was stirred at room temperature for 10 h to
(10) Wright, D. L.; Schulte, J. P., II; Page, M. A. Org. Lett. 2000, 2,
1847.
(11) Takeuchi, R.; Ue, N.; Tanabe, K.; Yamashita, K.; Shiga, N. J. Am.
Chem. Soc. 2001, 123, 9525.
(12) (a) Azzena, F.; Calvani, F.; Crotti, P.; Gardelli, C.; Macchia, F.;
Pineschi, M. Tetrahedron 1995, 51, 10601. (b) Bouzide, A.; Sauve´, G.
Tetrahedron Lett. 1997, 38, 5945. (c) Still, W. C.; Kahn, M.; Mitra, A. J.
Org. Chem. 1978, 43, 2923.
(13) (a) de Vries, A. H. M.; Meetsma, A.; Feringa, B. L. Angew. Chem.,
Int. Ed. 1996, 35, 2374. (b) Feringa, B. L.; Pineschi, M.; Arnold, L. A.;
Imbos, R.; de Vries, A. H. M. Angew. Chem., Int. Ed. 1997, 36, 2620.
7444 J. Org. Chem., Vol. 72, No. 19, 2007

SCHEME 2. Synthesis of Benzyloxyethyl-Substituted
Azacycloalkenes 6 and 7 Using 2c as a Key Intermediatea
hydroxyalkyl-substituted allylic carbonates 1a-c. It was also
found that the regioselectivities are largely dependent on the
length of the alkyl substituents, and thus, the benzyloxyethyl-
substituted allylic carbonate 1c showed high branch selectivity
(linear/branched ) >1/99) with very high enantioselectivity
(96% ee), whereas completely opposite regioselectivity (linear/
branched ) >99/1) was observed from the benzyloxymethyl-
substituted allylic carbonates 1a and 1b. Utilization of the
optically active N,O-dibenzylated 3-amino-1-penten-5-ol 2c as
a key intermediate permits the asymmetric synthesis of various
N,O-dibenzylated cyclic â-amino alcohol derivatives 6 and 7
through combination with ring-closing metathesis.
Experimental Section
Asymmetric Allylic Amination of Allylic Carbonates 1. A
typical procedure is given for the reaction of (E)-5-benzyloxy-2-
pentenyl methyl carbonate (1c). In a nitrogen-filled drybox, [Ir-
(COD)Cl]2 (9.4 mg, 14.0 µmol) and (Sa,Sc,Sc)-phosphoramidite L
(15.1 mg, 28.0 µmol) were diluted in 0.3 mL of THF and 0.3 mL
of n-propylamine in a 5 mL screw-capped vial. The reaction vial
was heated at 50 °C in a preheated oil bath for 30 min and then
allowed to cool to room temperature. All of the volatiles were
removed by blowing a stream of dry nitrogen gas, and the resulting
yellow residue was dried under vacuum. To the residual precatalyst
were added allylic carbonate 1a (350.0 mg, 1.4 mmol), benzylamine
(225.0 mg, 2.1 mmol), and 1.4 mL of THF. The vial was sealed
with a cap containing a PTFE septum and removed from the drybox,
and the reaction was stirred at room temperature for 10 h. After
evaporation of all volatiles, the ratio of regioisomers was 2c/3c )
a Conditions: (a) NaHCO3/cat. n-Bu4NI, CH3CN, reflux, 12 h; (b)
p-toluenesulfonic acid monohydrate (1.0 equiv), Grubbs’ second-generation
Ru-carbene catalyst (5 mol %)/CH2Cl2 (0.05 M), reflux, 10 h; (c) i-Pr2NEt,
CH2Cl2, 0 °C, 1 h; (d) Grubbs’ second-generation Ru-carbene catalyst (5
mol %)/CH2Cl2 (0.01 M), reflux, 12 h.
afford the branched amine 2c with extremely high regio- (>99%,
1
no 3c was detected in H NMR) and enantioselectivity (96%
ee) in a yield of 94% (entry 5, Table 1). However, under the
optimized asymmetric conditions (conditions B), as observed
in nonasymmetric allylic amination, only the linear-aminated
product 3a (2a/3b ) >1:99, 42%) and 3b (2b/3b ) >1:99,
27%) were formed from 1a and 1b, respectively. The reason
for the opposite regioselectivity between 1a (or 1b) and 1c is
not yet clear and remains to be elucidated.
1
>99:1 as determined by H NMR analysis of the crude mixture.
Silica gel column chromatography using 20% EtOAc/n-hexane
afforded (R)-N-[1-(2-benzyloxyethyl)-2-propenyl]benzylamine 2c
(369 mg, 94%). The absolute configuration of 2c was tentatively
assigned as R according to Hartwig’s model.6a The enantiomeric
excess of the allylic amination product 2c was determined to be
95.5% by HPLC analysis using a chiral column [Daicel CHIRAL-
CEL OD-H column (0.46 × 25 cm); eluent: n-hexane/2-propanol
) 95:5; flow rate ) 0.9 mL/min; retention time: 18.3 min (major),
27.3 min (minor)]. 2c: colorless oil; [R]D ) -5.56 (c 2.78, CHCl3);
1H NMR (400 MHz, CDCl3) δ 7.33-7.23 (m, 10H), 5.65 (ddd, J
) 17.6, 10.0, 8.3, 1H), 5.14 (d, J ) 10.0 Hz, 1H), 5.12 (d, J )
17.6 Hz, 1H), 4.49 (d of AB pattern, J ) 12.0 Hz, 1H), 4.45 (d of
AB pattern, J ) 12.0 Hz, 1H), 3.82 (d of AB pattern, J ) 13.1 Hz,
1H), 3.63 (d of AB pattern, J ) 13.1 Hz, 1H), 3.60-3.48 (m, 2H),
3.24 (dd, J ) 6.9, 7.6 Hz, 1H), 1.90-1.81 (m, 1H), 1.76-1.70 (m,
1H), 1.58 (br s, 1H); 13C NMR (100 MHz, CDCl3) δ 140.83, 140.61,
138.40, 128.33, 128.17, 127.64, 127.52, 126.77, 116.24, 73.0, 67.72,
58.95, 51.25, 35.63; HRMS m/z (FAB) calcd for C19H24NO (M +
H+) 282.1852, found 282.1854. 3c: 1H NMR (400 MHz, CDCl3)
δ 7.42-7.25 (m, 10H), 5.88-5.81 (m, 1H), 5.71-5.64 (m, 1H),
4.58 (s, 2H), 3.84 (s, 2H), 3.51 (t, J ) 6.5 H, 2H), 2.38 (q, J ) 6.6
Hz, 2H); 13C NMR (100 MHz, CDCl3) δ 138.2, 133.3, 128.3, 127.6,
127.5, 125.1, 72.9, 69.2, 68.3, 54.6, 52.9, 33.6.
Representative Procedure for the Ring-Closing Metathesis
of 4 To Give 6. p-Toluenesulfonic acid monohydrate (11.2 mg,
0.059 mmol) was added to a solution of 4a (19.0 mg, 0.059 mmol)
in dichloromethane (5 mL, 0.010 M), and the solution was stirred
for 30 min at room temperature until it became a homogeneous
solution. Grubbs’ monoimidazolinylidene monophosphine carbene
complex (second-generation catalyst, 2.5 mg, 2.9 µmol, 5 mol %)
was added, and the solution was stirred under reflux for 10 h. After
removal of the solvent, the residue was directly loaded on a silica
gel (EtOAc/Hex ) 1:4, containing 5% Et3N and 2% MeOH) to
afford 15.5 mg (89%) of pure 6a: pale yellow oil; [R]D ) -48.2
(c 1.0, CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.40-7.20 (m, 10H),
5.77-5.70 (m, 2H), 4.49 (s, 2H), 4.03 (d of ABq, J ) 13.2 Hz,
With a gram quantity of the key intermediate chiral allyl
amine 2c in hand, we next attempted synthesis of various
2-benzyloxyethyl-substituted azacycloalkenes 6 and 7 via ring-
closing metathesis (Scheme 2). For this purpose, dienes 4a-d
were prepared in a straightforward manner by N-alkylation of
2c with the corresponding bromoalkenes in high yields (90-
94%). Due to catalyst inhibition by basic nitrogen, a variety of
methods for blocking basic nitrogen function for Ru-based RCM
reactions were employed, involving Bro¨nsted or Lewis acids.10,14
In our case, Wright’s protocol employing an equivalent amount
of p-toluenesulfonic acid (p-TsOH·H2O)10 as an additive worked
best for RCM of amines 4a-d, where the Grubbs’ second-
generation catalyst showed superior catalytic efficiency com-
pared with the Grubbs’ first-generation catalyst.15 With 5 mol%
of Grubbs’ second Ru-carbene catalyst, five- to eight-
membered azacycles 6a-d were synthesized uneventfully in
high yields. The RCM of the amide dienes 5a-c, on the other
hand, was carried out in the absence of an acid with 5 mol %
of Grubbs second Ru-carbene catalyst, affording the corre-
sponding five- to seven-membered pyrrolidinone analogues
7a-c in high yields. It should be noted that these azacycloalk-
enes represent a useful platform for a variety of N-heterocyclic
compounds.
In summary, we have developed a new route for enantiose-
lective synthesis of N,O-protected 3-amino-1-penten-5-ol through
investigation of the Ir-catalyzed allylic amination of O-protected
(14) (a) Fu, G. C.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc.
1993, 115, 9856. (b) Fu¨rstner, A.; Langmann, K. J. J. Am. Chem. Soc. 1997,
64, 5321. (c) Yang, Q.; Xiao, W. J.; Yu, Z. Org. Lett. 2005, 7, 871.
(15) (a) Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995,
28, 446. (b) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett.
1999, 1, 953.
J. Org. Chem, Vol. 72, No. 19, 2007 7445

1H), 3.75 (m, 1H), 3.71-3.56 m, 3), 3.54 (d of ABq, J ) 13.5 Hz,
1H), 3.21-3.14 (m, 1H), 1.94-1.78 (m, 2H); 13C NMR (100 MHz,
CDCl3) δ 140.4, 138.8, 131.6, 128.8, 128.6, 128.5, 127.8, 127.7,
127.1, 127.0, 73.2, 68.4, 68.0, 60.4, 59.4, 35.3; HRMS m/z (FAB)
calcd for C20H24NO (M + H+) 294.1852, found 294.1851.
1.78 (m, 1H); 13C NMR (100.62 MHz, CDCl3) δ 171.6, 148.5,
138.1, 137.7, 128.9, 128.6, 128.05, 128.0, 127.9, 127.7, 126.7, 73.4,
66.0, 60.5, 60.4, 43.8; HRMS m/z (FAB) calcd for C20H22NO2 (M
+ H+) 308.1645, found 308.1647.
Representative Procedure for the Ring-Closing Metathesis
of 5 To Give 7. Grubbs’ monoimidazolinylidene monophosphine
carbene complex (second-generation catalyst, 2.2 mg, 2.6 µmol, 3
mol %) was added to a solution of 5a (26.0 mg, 0.078 mmol) in
dichloromethane (0.8 mL, 0.1 M), and the solution was stirred at
room temperature for 10 h. Then, an additional 3% of Grubbs’
second-generation catalyst was added, and the mixture was stirred
under reflux for a further 10 h. Thin layer chromatography indicated
complete conversion, and the reaction mixture was directly loaded
on a silica gel and purified (EtOAc/Hex ) 1:1) to afford the ring-
closed product 7a: pale yellow oil (90%); [R]D ) -23.5 (c 1.0,
CHCl3); 1H NMR (400 MHz, CDCl3) δ 7.40-7.15 (m, 10H), 7.10
(dd, J ) 1.5, 5.9 Hz, 1H), 6.17 (dd, J ) 1.9, 5.8 Hz, 1H), 5.10 (d
of ABq, J ) 15.0 Hz, 1H), 4.41 (s, 2H), 4.12 (d of ABq, J ) 15.0
Hz, 1H), 4.15-4.06 (m, 1H), 3.45-2.36 (m, 2H), 2.15 (m, 1H),
Acknowledgment. This work was supported by the Center
for Molecular Design and Synthesis (for S.-g.L.) and the Basic
Research Program (R01-2006-000-10426-0 for S.-g.L. and R01-
2006-000-11283-0 for S.S.) from KOSEF and the Seoul R&BD
Program (10816) (S.-g.L.) and the Korean Research Foundation
(KRF-R-14-2002-04500100 for J.K.).
Supporting Information Available: Detailed experimental
procedures and spectroscopic data, 1H and 13C spectra of compounds
2c, 4a-d, 5a-c, 6a-d, and 7a-c. This material is available free
of charge via the Internet at http://pubs.acs.org.
JO070998H
7446 J. Org. Chem., Vol. 72, No. 19, 2007