Stereoselective Conjugate Addition of the Lithium Anion of N-Allyl Imine to Unsaturated Esters: Application to the Enantiospecific Total Synthesis of (-)-Epibatidine

Article abstract of DOI:10.1021/acs.joc.9b01340

A regio- and diastereoselective conjugate addition of the lithium anion of N-allyl imine (prepared from allylamine and benzophenone) to α,β-unsaturated esters in good yields is reported. The reaction was general and provided the γ-amino esters resulting from the regioselective C-C bond formation between the α-carbon to the nitrogen in the imine and the β-carbon of the unsaturated ester. Synthetic utility of the formed products was illustrated in the nonracemic total synthesis of the bioactive alkaloid (-)-epibatidine.

Full text of DOI:10.1021/acs.joc.9b01340

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Article
Stereoselective Conjugate Addition of the Lithium Anion
of N-allyl Imine to Unsaturated Esters: Application to
the Enantiospecific Total Synthesis of (-)-Epibatidine
Kavirayani R Prasad, and Manoj B Uphade
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.9b01340 • Publication Date (Web): 11 Jul 2019
Downloaded from pubs.acs.org on July 11, 2019
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The Journal of Organic Chemistry
Stereoselective Conjugate Addition of the Lithium Anion of N-allyl Imine to
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Unsaturated Esters: Application to the Enantiospecific Total Synthesis of ()-
Epibatidine
Kavirayani R. Prasad* and Manoj B. Uphade
Department of Organic Chemistry, Indian Institute of Science, Bangalore 560012, India
E-mail: prasad@iisc.ac.in; FAX: +918023600529
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Abstract: A regio and diastereoselective conjugate addition of the lithium anion of N-allyl imine
(
prepared from allylamine and benzophenone) to ,-unsaturated esters in good yields is reported.
The reaction was general and provided the -amino esters resulting from the regioselective C-C bond
formation between the carbon -to the nitrogen in the imine and the -carbon of the unsaturated
ester. Synthetic utility of the formed products was illustrated in the non-racemic total synthesis of the
bio-active alkaloid ()-epibatidine.
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Introduction
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Aza-allyl anions, which are broadly classified into non-stabilized, semi-stabilized and stabilized anions
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depending on the substitutions on the imine are important intermediates in organic synthesis. The
seminal observation by Kaufmann that deprotonation of the benzylidineimine (obtained from
benzaldehyde and benzylamine) forms the semi-stabilized aza-allyl anion and reacts with stilbene to
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form the (32) cycloaddition product, invigorated considerable interest to explore the reactivity of 2-
aza-allyl anions (Fig. 1). Pearson’s group contributed extensively to the synthesis and reactivity of non-
stabilized and semi-stabilized aza-allyl lithium anions by tin-lithium exchange reaction of stannyl
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substituted imines and widely utilized these intermediates in the total synthesis of alkaloids. The
pioneering work of O’Donnell established a general route for the asymmetric synthesis of -amino
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acid derivatives by the formation of stabilized aza-allyl anions from glycine ester based ketimines. The
procedure involved the deprotonation of the imine using catalytic amount of chiral phase transfer
catalyst (PTC) and further reaction with various electrophiles including alkyl halides and unsaturated
esters. Churma’s group studied the generation of semi-stabilized 2-aza-allyl anions via decarboxylation
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of diphenylglycine derived imines and their reactions with electrophiles. Yee and Dyranska et. al.
independently reported the generation of aza-allyl anions from the ketimines obtained from
benzylamine and 2-aminomethyl pyridine and benzophenone with NaOH under phase transfer
conditions and their subsequent addition to unsaturated cinammate esters. Recently, an elegant
strategy for the synthesis of semi-stabilized aza-allyl anions from ketimines exploring the umpolung
reactivity of the ketimines using chiral phase transfer catalysts was disclosed by Deng’s group.
Excellent enantioselectivities were obtained in protonation as well as reaction with electrophiles such
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as , -unsaturated aldehydes. Buchwald’s group studied the reactivity of semi-stabilized 2-aza-allyl
anions with aryl halides and aryl triflates under palladium catalysis in an asymmetric fashion to form
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the -aryl amines. Metal catalyzed generation of the 1,3-dipole (N-metalated azo-methine ylides)
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from amino esters and aldehydes and their cycloaddition reaction with acrylates to yield substituted
pyrrolidines is a procedure that is well documented in literature.10
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Fig. 1 Known routes for the generation of 2-aza-allyl anions and their reaction with electrophiles
While there has been an active interest for the synthesis of the semi-stabilized aza-allyl anions and
their reactivity with electrophiles, a few examples were recorded in the literature for the generation of
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-aza-pentadienyl anion and its reaction with electrophiles. Wolf and Wurthwein were the first to
study the generation and reactivity of the lithium carbanion of 1,1-diphenyl-2-aza-pentadiene 2a
obtained by deprotonation of the imine 1a) and its reaction with aldehydes/ketones. The nucleophilic
(
attack of either the C3 or C5 carbon of the metalated species 2a on aldehydes and ketones furnishes
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the corresponding amino alcohol 3 or the allylation product 4 (eq.1, Fig 2). They found that the
reaction of 2a with aliphatic aldehydes proceeded with very good regioselectivity producing the
protected 3-amino-1-alkene-4-ol 3a, while reaction with the ketones furnished a mixture of 3a and 4a
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resulting from the nucleophilic addition at the C3 and C5 positions of 2a respectively. Similar outcome
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was reported by Epifani et. al. in their investigations concerning the generation of 1-benzothiazolyl-2-
aza-pentadienyl lithium 2b from the imine 1b and further reaction with aldehydes and ketones.12
Barrett’s group utilized either enantiomer of diisopinocamphenyl chloroborane as the electrophile in
quenching the lithium carbanion 2a to yield the borane derivative 5. The formed boranes reacted with
various aromatic aldehydes to produce the amino alcohols 3 with excellent diastereo and
enantioselectively (eq. 1, Fig 2).13 Deng’s group extended their strategy of chiral PTC catalyzed
generation of semi-stabilized aza-allyl anions to , -unsaturated ketimines and proposed the
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intermediacy of 2-aza-pentadienyl anion in the reaction with acrolein (eq. 2, Fig. 2). Walsh group
investigated the arylation reactions of aza-allyl--palladium complexes formed from the 2-aza-
pentadienyl anion intermediates which were synthesized from the umpolung deprotonation of imines
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obtained from cinammaldehyde and diphenylmethyl amine (eq. 3, Fig. 2). Inspite of the incorporation
of the useful allylamine functionality in nucleophilic addition reaction, no further utility of the
carbanion 2a was recorded in the literature. We reasoned that the reaction of 2a with ,-unsaturated
esters 6 should proceed with the C3 attack of the nucleophile in a 1,4-conjugate addition pathway. The
reaction will generate the product 7 containing the amine, ester and alkene functionalities; useful for
further synthetic elaboration (eq. 4, Fig. 2). Herein, we report in detail our investigation of the above
reaction and application of the resulting -amino esters in the asymmetric total synthesis of the bio-
active alkaloid ()-epibatidine.
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Fig. 2 Synthesis and reactions of 2-aza-allyl anions with electrophiles
Results and Discussion
Our study commenced with the addition of carbanion 2a generated by reaction of 1a with LDA to the
cinammate ester 6a. The reaction resulted in a mixture of products 7a and 8a in 25% and 36% yields,
respectively, arising from the nucleophilic addition at the C3 and C5 positions of the carbanion 2a.
Addition of MgBr to 2a prior to the addition of the ester 6a improved the ratio for the formation of 7a
2
n
and 8a to 41% and 12% respectively. Interestingly, generation of the anion 2a from 1a using BuLi in
presence of TMEDA and further addition to the unsaturated ester improved the yield of 7a to 64% and
the other product 8a was isolated in 6% yield (Scheme 1).
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Scheme 1. Addition of the lithium anion 2a generated from 1a to the unsaturated ester 6a
After establishing the optimized condition for the addition of carbanion 2a to the unsaturated ester 6a,
generality of the reaction was investigated with a number of unsaturated esters having aromatic
substitution. It was found that the reaction proceeded smoothly to furnish 7b-m arising from the
addition of C3 carbon of 2 as the major product in good yields. Substitution on the aromatic ring in the
unsaturated ester 6 also significantly influenced the product outcome. Electron rich substitution at the
4-position of the aromatic ring in the unsaturated ester 6, in general afforded 7 as the major product.
As evident from chart -1, 4-methoxy substitution on the aromatic ring furnished the product 7c in 71%
yield, with no formation of the product 8c arising from the addition at the C5-position of carbanion 2a.
The presence of 4-Cl and 4-Me substitution on the aromatic ring afforded the major products 7d and
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e in 69% and 58% yield respectively, while the minor products 8d and 8e were also isolated in 11%
i
and 6% yields. Presence of the Pr and CF groups at the 4-position of the aromatic ring furnished the
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products 7f and 7g in 55% and 42% yields respectively. However, the introduction of bulky bromine
substitution at the 2-position of the aromatic ring diminished the regioselectivity and afforded the
products 7j and 8j in 35% and 43% yields respectively. The reaction with unsaturated ester 6l
containing the hetero-aromatic furan ring also furnished the major product 7l in 51% yield and the
minor product 8l was isolated in 11% yield. Reaction of the unsaturated ester comprising the 6-chloro-
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3
-pyridyl substitution furnished the product in 56% yield accompanied by the formation of 8m in 7% of
yield. We also observed the formation of the minor syn isomer 7m’ in 4% yield. The reaction of
carbanion 2 with ethyl crotonate afforded the product 7n in 49% yield. All these results are
summarized in chart -1. The relative stereochemistry of the product is further confirmed by the X-ray
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crystal structure analysis of 7j. The observed diastereoselectivity can be explained by the transition
state (Fig 3) proposed by Yee for an analogous reaction.6
Chart-1 Diastereoselective Addition of 2-Aza-allyl pentadienyl anion 1a to , -unsaturated esters 6a-o
a
b
All reactions were carried out in THF as solvent at 78 C. Yields refer to isolated yields after
c
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chromatography. The diastereomeric ratio was determined by H NMR of the reaction mixture
obtained after removing the excess imine 1a by column chromatography.
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n
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We attempted the chiral version of the reaction by employing BuLi/ ()-sparteine as a base in the
deprotonation of 1a and further addition to 6b. However, no asymmetric induction was observed and
racemic 7b was isolated in 31% yield. Interestingly, addition of the carbanion 2a to the unsaturated
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imide 9a derived from Evans’ chiral oxazolidinone furnished the major diastereomer 10a in 58%
yield. Similarly, addition to the imides 9b and 9c afforded the products 10b and 10c in 59% and 58%
yields respectively (Scheme 2).
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Scheme 2. Addition of the carbanion 2a to the imides derived from chiral oxazolidinones 9a-c
Deprotection of the imine functionality in product 7 with hydroxylamine cleanly furnished the lactams
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1-14 in good yields. Similarly, the reaction of oxazolidinones 10a-b with hydroxylamine afforded the
chiral lactams 12 and 13 in almost quantitative yield (Scheme 3).
Scheme 3. Synthesis of the lactams 11-14 from the imino ester 7
The formed lactams are useful intermediates in the synthesis of natural products and an application of
the lactam 13 in the total synthesis of the alkaloid natural product ()-epibatidine (15) was
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accomplished as shown below. Synthesis of ()-15 was envisaged from the known alcohol 16, the
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synthesis of which was planned by RCM of the amino ketone 17. Formation of 17 is anticipated by
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elaboration of the lactam 13 (Scheme 4).
H
Cl
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N
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Ar
Boc
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Ar
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3 Ar = 6-chloro-3-pyridyl
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H
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Scheme 4. Retrosynthesis for ()-epibatidine (15)
Thus, reaction of the lactam 13 with Boc anhydride furnished the N-Boc lactam 18 in 98% yield.
2
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Addition of vinylmagnesium bromide to 18 afforded the amino ketone 17 in 64% yield. Ring closing
metathesis of the diene in 17 with Grubbs’ second-generation catalyst provided the cyclohexenone 19
in 82% yield, which on reaction with NaBH / NiCl furnished the amino alcohol 16 in 75% yield. Using a
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procedure that was described earlier, alcohol 16 was transformed to the bromide 20. Deprotection of
the Boc group and concomitant displacement of the bromide with the free amine yielded epibatidine
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5 (Scheme 5), which exhibited satisfactory physical and spectral characteristics to that reported in
literature.21c The synthesis also confirmed the sense of induction observed in the formation of 10b in
the reaction of 2-aza-pentadienyl anion 2a with oxazolidinone 9b.
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O
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BOC) O
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DMAP, CH CN
MgBr
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NH
NBoc
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°C to rt, 2 h
8%
Ar
Ar
THF, 10 °C
0 min, 64%
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3
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3
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Ar = 6-chloro-3-pyridyl
O
O
NaBH4
G-II (0.05 eq)
NiCl 6H O
2 2
MeOH, 0 °C
40 min, 75%
CH Cl , 
2
2
Ar
Ar
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h, 82%
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NHBoc
NHBoc
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17
OH
Br
i) MsCl, Et N, CH Cl , 0 °C, 20 min
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1%
Ar
Ar
ii) LiBr, THF, , 36 h, 43%
NHBoc
NHBoc
20
1
6
Cl
N
H
N
i) TFA, CH Cl , 0 °C to rt, 1.0 h
2
2
ii) CHCl , , 72 h, 39%
3
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Scheme 5. Total synthesis of ()-epibatidine
conclusion
In conclusion, we have developed a useful regio and diastereoselective conjugate addition of lithium
carbanion of 1,1-diphenyl-2-aza-pentadiene to ,-unsaturated esters. An asymmetric version of the
reaction was also accomplished using unsaturated imides derived from Evans’ chiral oxazolidinones.
Application of the products formed in the reaction was demonstrated in the total synthesis of alkaloid
natural product ()-epibatidine.
Experimental:
General Information: Column chromatography was performed on silica gel, Acme grade 100−200
mesh. TLC plates were visualized either with UV in an iodine chamber or with phosphomolybdic acid
spray unless noted otherwise. All reagents were purchased from commercial sources and used without
additional purification. THF was freshly distilled over Na-benzophenone ketyl. Melting points were
recorded using melting point apparatus in capillary tubes and are uncorrected. Unless stated
1
13
otherwise, H (400 MHz) and C (100 MHz) spectra were recorded on 400 MHz spectrophotometers in
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CDCl as solvent with TMS as reference. High-resolution mass spectra (HRMS) were recorded on a Q-
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
TOF micromass spectrometer using electron spray ionization mode.
General Procedures for the addition of lithium anion of allyl imine to various conjugated ester: The
following procedure for the addition of lithium anion of allyl imine 1a to ethyl (E)-3-
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(benzo[d][1,3]dioxol-5-yl)acrylate is representative.
O
O
O
OEt
N
Ph
Ph 7a
Ethyl 3-(benzo[d][1,3]dioxol-5-yl)-4-((diphenylmethylene)amino)hex-5-enoate (7a): In a 50 mL two-
neck round bottom flask equipped with argon balloon were added TMEDA (0.13 mL, 0.9 mmol) in THF
(3 mL) at –78°C followed by nBuLi (0.9 mL of 1.0 M in hexane, 0.9 mmol) and stirred for 10 min. A
solution of the allyl imine 1a (0.2 g, 0.9 mmol) in THF (3 mL) was introduced into the flask and the
resulting red colored solution was stirred for 30 min at the same temperature. A solution of ethyl (E)-3-
(benzo[d][1,3]dioxol-5-yl)acrylate (0.132 g, 0.6 mmol) in THF (3 mL) was added dropwise to the
reaction mixture and was stirred for 2 h at the same temperature. After completion of the reaction
(
TLC), it was quenched by addition of saturated aqueous solution of NH Cl (5 mL) and extracted with
4
Et O (3 × 10 mL). The combined organic layers were washed with brine (5 mL) and dried over
2
anhydrous Na SO . Evaporation of solvent gave the crude residue, which was purified by silica gel
2
4
column chromatography using petroleum ether/EtOAc (9.5:0.5) as eluent to furnish 7a (0.168 g, 64%)
and 8a (15 mg, 6%) as a colorless oil. 7a: R 0.4 (Petroleum ether/EtOAc, 9:1). IR (Neat):  2927,
f
max

1 1
1
6
732, 1622, 1489, 1244, 1038 cm . H NMR (400 MHz, CDCl ):  7.71 (d, J = 6.8 Hz, 2H), 7.48-7.32 (m,
3
H), 7.00-6.87 (m, 2H), 6.68 (d, J = 8.4 Hz, 1H), 6.67-6.58 (m, 2H), 5.98-5.81 (m, 3H), 5.03 (dt, J = 10.8,
1.6 Hz, 1H), 4.93 (dt, J = 17.2, 1.6 Hz, 1H), 3.99 (q, J = 7.2 Hz, 3H), 3.51 (quint, J = 5.6 Hz, 1H), 2.95 (dd,
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1
3
1
J= 15.6, 5.2 Hz, 1H), 2.73 (dd, J = 15.6, 10.4 Hz, 1H), 1.10 (t, J = 7.2 Hz, 3H). C{ H} NMR (100 MHz,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
CDCl ):  172.5, 168.2, 147.2, 145.9, 139.3, 138.5, 136.4, 135.4, 130.0, 128.4 (2C), 128.2, 128.1 (2C),
3
1
27.9 (2C), 127.1 (2C), 121.4, 115.4, 108.6, 107.7, 100.6, 69.3, 60.0, 47.6, 36.9, 13.9. HRMS (ESI-TOF)
+
m/z: [M+H] Calcd for C H NO 442.2018; Found: 442.2017.
28 28
4
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
O
O
O
OEt
Ph
N
Ph
8a
Ethyl (Z)-3-(benzo[d][1,3]dioxol-5-yl)-6-((diphenylmethylene)amino)hex-5-enoate (8a): Rf 0.3

1 1
(
Petroleum ether/EtOAc, 9:1). IR (Neat): max 2924, 1731, 1658, 1489, 1243, 1036 cm . H NMR (400
MHz, CDCl ):  7.63 (dd, J = 6.8, 1.6 Hz, 2H), 7.45 (dd, J = 4.8, 2.0 Hz, 3H), 7.40-7.27 (m, 4H), 7.12 (d, J =
3
4
1
.4 Hz, 1H), 7.11 (d, J = 2.0 Hz, 1H), 6.73 (d, J = 7.6 Hz, 1H), 6.70-6.56 (m, 2H), 6.05 (dt, J = 12.8, 7.6 Hz,
H), 5.93 (s, 1H), 5.92 (s, 1H), 4.04 (q, J = 7.2 Hz, 2H), 3.17 (quint, J = 7.6 Hz, 1H), 2.63 (dd, J = 15.2, 6.8
13
1
Hz, 1H), 2.50 (dd, J = 15.2, 8.8 Hz, 1H), 2.37 (t, J = 7.6 Hz, 2H), 1.15 (t, J = 7.2 Hz, 3H). C{ H} NMR (100
MHz, CDCl ):  172.1, 165.6, 147.6, 146.0, 139.8, 139.5, 137.3, 136.2, 130.2, 130.1, 128.8 (2C), 128.7
3
(2C), 128.3 (2C), 128.0 (2C), 126.0, 120.6, 108.1, 107.8, 100.8, 60.2, 42.0, 41.0, 37.4, 14.1. HRMS (ESI-
+
TOF) m/z: [M+H] Calcd for C H NO 442.2018; Found: 442.2019.
2
8
28
4
O
OEt
N
Ph
Ph 7b
Ethyl 4-((diphenylmethylene)amino)-3-phenylhex-5-enoate (7b): Following the general procedure,
addition of lithium anion of 1 (0.398 g, 1.8 mmol) to ethyl cinnamate (0.212 g, 1.2 mmol) furnished 7b
(0.287 g, 60%) and 8b (30 mg, 6%) as a colorless oil. 7b: R 0.6 (Petroleum ether/EtOAc, 9.5:0.5). IR
f
1
1
(
Neat): max 3060, 1732, 1623, 1248, 1156 cm . H NMR (400 MHz, CDCl ):  7.65 (d, J = 7.2 Hz, 2H),
3
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7
1
5
.45-7.25 (m, 6H), 7.25-7.10 (m, 3H) 7.07 (d, J = 6.8 Hz, 2H), 6.75 (d, J = 6.8 Hz, 2H), 5.86 (ddd, J = 16.8,
0.4, 5.6 Hz, 1H), 5.00 (d, J = 10.4 Hz, 1H), 4.89 (d, J = 17.2 Hz, 1H), 4.05-3.85 (m, 3H), 3.52 (quint, J =
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
.6 Hz, 1H), 2.97 (dd, J = 15.6, 4.8 Hz, 1H), 2.81 (dd, J = 15.6, 10.0 Hz, 1H), 1.04 (t, J = 7.2 Hz, 3H).
1
3
1
C{ H} NMR (100 MHz, CDCl ):  172.8, 168.3, 141.7, 139.5, 138.7, 136.5, 130.1, 128.51 (2C), 128.50
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(2C), 128.1 (2C), 128.03 (2C), 128.01 (3C), 127.2 (2C), 126.4, 115.6, 69.3, 60.1, 48.0, 36.3, 14.0. HRMS
+
(ESI-TOF) m/z: [M+Na] Calcd for C H NO Na 420.1939; Found: 420.1941.
2
7
27
2
O
OEt
Ph
N
Ph
8b
Ethyl (Z)-6-((diphenylmethylene)amino)-3-phenylhex-5-enoate (8b): R 0.5 (Petroleum ether/EtOAc,
f
1
1
9
.5:0.5). IR (Neat): max 3437, 2928, 1732, 1658, 1277, 1154 cm . H NMR (400 MHz, CDCl ):  7.61 (d,
3
J = 7.2 Hz, 2H), 7.48-7.41 (m, 3H), 7.40-7.28 (m, 6H), 7.18 (dd, J = 13.6, 7.2 Hz, 2H), 7.13-7.02 (m, 2H),
6
1
.63 (d, J = 12.8 Hz, 1H), 6.05 (dt, J = 12.8, 8.0 Hz, 1H), 4.01 (q, J = 7.2 Hz, 2H), 3.23 (quint, J = 7.6 Hz,
H), 2.67 (dd, J = 15.2, 6.4 Hz, 1H), 2.55 (dd, J = 15.2, 8.4 Hz, 1H), 2.41 (t, J = 7.6 Hz, 2H), 1.11 (t, J = 7.2
1
3
1
Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  172.2, 165.6, 143.4, 139.8, 139.6, 136.2, 130.3, 130.1, 128.8
3
(2C), 128.75 (2C), 128.6, 128.5, 128.38 (2C), 128.35 (2C), 128.1, 127.5, 126.51, 126.50, 60.3, 42.2, 40.7,
+
37.4, 14.1. HRMS (ESI-TOF) m/z: [M+H] Calcd for C H NO 398.2120; Found: 398.2123.
2
7
28
2
OMe
O
OEt
N
Ph
Ph 7c
Ethyl 4-((diphenylmethylene)amino)-3-(4-methoxyphenyl)hex-5-enoate (7c): Following the general
procedure, addition of lithium anion of 1 (0.2 g, 0.9 mmol) to ethyl (E)-3-(4-methoxyphenyl)acrylate
(0.124 g, 0.6 mmol) furnished 7c (0.183 g, 71%) as a colorless oil. R 0.4 (Petroleum ether/EtOAc, 9:1).
f
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
1 1
IR (Neat): max 3301, 2924, 1732, 1617, 1512, 1248 cm . H NMR (400 MHz, CDCl ):  7.66 (dt, J = 6.8,
3
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
1.6 Hz, 2H), 7.45-7.25 (m, 6H), 6.99 (dd, J= 6.8, 2.0 Hz, 2H), 6.81 (d, J = 6.8 Hz, 2H), 6.74 (dd, J = 6.8, 2.0
Hz, 2H), 5.85 (ddd, J = 17.2, 10.4, 5.2 Hz, 1H), 4.99 (dt, J = 10.4, 1.6 Hz, 1H), 4.88 (dt, J = 17.2, 1.6 Hz,
1
H), 3.93 (q, J = 7.2 Hz, 3H), 3.73 (s, 3H), 3.48 (quint, J = 5.6 Hz, 1H), 2.93 (dd, J = 15.6, 4.8 Hz, 1H), 2.75
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
13
1
(
dd, J = 15.6, 10.4 Hz, 1H), 1.05 (t, J = 7.2 Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  172.8, 168.2, 158.1,
3
1
1
39.5, 138.8, 136.5, 133.7, 130.0, 129.3 (2C), 128.5 (2C), 128.11, 128.10 (2C), 128.0 (2C), 127.2 (2C),
+
15.5, 113.4 (2C), 69.4, 60.1, 55.1, 47.1, 36.7, 14.0. HRMS (ESI-TOF) m/z: [M+Na] Calcd for
C H NO Na 450.2045; Found: 450.2046.
2
8
29
3
Cl
O
OEt
N
Ph
Ph 7d
Ethyl 3-(4-chlorophenyl)-4-((diphenylmethylene)amino)hex-5-enoate (7d): Following the general
procedure, addition of lithium anion of 1 (0.2 g, 0.9 mmol) to ethyl (E)-3-(4-chlorophenyl)acrylate
(0.126 g, 0.6 mmol) furnished 7d (0.180 g, 69%) and 8d (29 mg, 11%) as a colorless oil. 7d: R 0.4
f

1 1
(
Petroleum ether/EtOAc, 9.5:0.5). IR (Neat): max 2980, 1733, 1622, 1490, 1248, 1158 cm . H NMR
(400 MHz, CDCl ):  7.65 (d, J = 7.6 Hz, 2H), 7.44-7.26 (m, 6H), 7.16 (d, J = 8.0 Hz, 2H), 7.01 (d, J = 8.4
3
Hz, 2H), 6.78 (d, J = 6.4 Hz, 2H), 5.84 (ddd, J = 16.8, 10.4, 5.6 Hz, 1H), 5.02 (d, J = 10.4 Hz, 1H), 4.90 (d, J
= 17.2 Hz, 1H), 3.94 (q, J = 7.2 Hz, 3H), 3.50 (quint, J = 5.2 Hz, 1H), 2.96 (dd, J = 15.6, 5.2 Hz, 1H), 2.80
1
3
1
(
dd, J = 15.6, 10.4 Hz, 1H), 1.05 (t, J = 7.2 Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  172.5, 168.5, 140.3,
3
139.3, 138.3, 136.3, 132.1, 130.1, 129.8 (2C), 128.5 (2C), 128.2, 128.13 (2C), 128.10 (2C), 128.0 (2C),
+
1
4
27.1 (2C), 115.9, 69.1, 60.2, 47.3, 36.0, 14.0. HRMS (ESI-TOF) m/z: [M+H] Calcd for C H ClNO
2
7
27
2
32.1730; Found: 432.1734.
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Cl
1
2
3
4
5
O
OEt
Ph
N
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Ph
8d
Ethyl (Z)-3-(4-chlorophenyl)-6-((diphenylmethylene)amino)hex-5-enoate (8d): R 0.2 (Petroleum
f
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0

1 1
ether/EtOAc, 9.5:0.5). IR (Neat): max 3372, 2925, 1731, 1658, 1275, 1020 cm . H NMR (400 MHz,
CDCl ):  7.60 (d, J = 7.6 Hz, 2H), 7.48-7.40 (m, 2H), 7.40-7.28 (m, 4H), 7.25 (d, J = 7.6 Hz, 2H), 7.09 (d, J
3
=
8.4 Hz, 2H), 7.08-7.00 (m, 2H), 6.56 (d, J = 12.8 Hz, 1H), 6.01 (dt, J = 13.2, 7.6 Hz, 1H), 4.01 (q, J = 7.2
Hz, 2H), 3.21 (quint, J = 8.0 Hz, 1H), 2.66 (dd, J = 15.2, 6.4 Hz, 1H), 2.54 (dd, J = 15.2, 8.8 Hz, 1H), 2.48-
1
3
1
2
.28 (m, 2H), 1.12 (t, J = 7.2 Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  171.9, 165.9, 141.8, 140.0, 139.5,
3
137.5, 136.1, 132.4, 132.1, 130.2, 130.0 (2C), 129.6, 129.0, 128.75, 128.7 (2C), 128.5 (2C), 128.4, 128.3,
+
1
28.1, 60.4, 41.6, 40.5, 37.3, 14.1. HRMS (ESI-TOF) m/z: [M+H] Calcd for C H ClNO 432.1730;
2
7
27
2
Found: 432.1731.
Me
O
OEt
N
Ph
Ph 7e
Ethyl 4-((diphenylmethylene)amino)-3-(p-tolyl)hex-5-enoate (7e): Following the general procedure,
addition of lithium anion of 1 (0.2 g, 0.9 mmol) to ethyl (E)-3-(p-tolyl)acrylate (0.114 g, 0.6 mmol)
furnished 7e (0.144 g, 58%) and 8e (15 mg, 6%) as a colorless oil. 7e: R 0.6 (Petroleum ether/EtOAc,
f

1 1
9
.5:0.5). IR (Neat): max 3399, 3057, 1734, 1623, 1445, 1248 cm . H NMR (400 MHz, CDCl ):  7.66 (d,
3
J = 7.6 Hz, 2H), 7.42-7.25 (m, 6H), 6.97 (q, J = 8.4 Hz, 4H), 6.79 (d, J = 6.4 Hz, 2H), 5.85 (ddd, J = 17.2,
1
6
0.4, 5.6 Hz, 1H), 4.98 (d, J = 10.4 Hz, 1H), 4.88 (d, J = 17.2 Hz, 1H), 4.05-3.85 (m, 3H), 3.50 (quint, J =
.0 Hz, 1H), 2.94 (dd, J = 15.6, 5.2 Hz, 1H), 2.76 (dd, J = 15.6, 10.0 Hz, 1H), 2.25 (s, 3H), 1.04 (t, J = 7.2
1
3
1
Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  172.7, 168.1, 139.5, 138.7, 138.5, 136.5, 135.7, 130.0, 128.6
3
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(
2C), 128.4 (2C), 128.2 (2C), 128.0 (3C), 127.9 (2C), 127.2 (2C), 115.4, 69.3, 60.0, 47.5, 36.6, 20.9, 13.9.
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
HRMS (ESI-TOF) m/z: [M+H] Calcd for C H NO 412.2277; Found: 412.2275.
28 30
2
Me
O
OEt
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Ph
N
Ph
8e
Ethyl (Z)-6-((diphenylmethylene)amino)-3-(p-tolyl)hex-5-enoate (8e): R 0.4 (Petroleum ether/EtOAc,
f

1 1
9
.5:0.5). IR (Neat): max 3380, 2924, 1731, 1660, 1274, 1024 cm . H NMR (400 MHz, CDCl ):  7.60 (d,
3
J = 7.2 Hz, 2H), 7.48-7.38 (m, 2H), 7.37-7.28 (m, 4H), 7.16-7.00 (m, 6H), 7.62 (d, J = 12.8 Hz, 1H), 6.05
dt, J = 20.8, 7.6 Hz, 1H), 4.00 (q, J = 7.2 Hz, 2H), 3.18 (quint, J = 7.6 Hz, 1H), 2.64 (dd, J = 15.2, 6.8 Hz,
(
1
3
1
1H), 2.51 (dd, J = 15.2, 8.8 Hz, 1H), 2.38 (t, J = 7.6 Hz, 2H), 2.31 (s, 3H), 1.11 (t, J = 7.2 Hz, 3H). C{ H}
NMR (100 MHz, CDCl ):  172.3, 165.5, 140.4, 139.7, 139.6, 137.6, 136.2, 135.9, 132.4, 130.6, 130.12,
3
130.10 (2C), 129.1, 128.83, 128.8, 128.7, 128.4, 128.3 (2C), 128.1, 127.4, 60.2, 41.8, 40.8, 37.5, 21.1,
+
1
4.1. HRMS (ESI-TOF) m/z: [M+H] Calcd for C H NO 412.2277; Found: 412.2278.
2
8
30
2
Me
Me
O
OEt
N
Ph
Ph 7f
Ethyl 4-((diphenylmethylene)amino)-3-(4-isopropylphenyl)hex-5-enoate (7f): Following the general
procedure, addition of lithium anion of 1 (0.2 g, 0.9 mmol) to ethyl (E)-3-(4-isopropylphenyl)acrylate
(0.131 g, 0.6 mmol) furnished 7f (144 mg, 55%) as a colorless oil. R 0.5 (Petroleum ether/EtOAc,
f

1 1
9
.5:0.5). IR (Neat): max 2963, 1734, 1624, 1247, 1157 cm . H NMR (400 MHz, CDCl ):  7.65 (d, J = 6.8
3
Hz, 2H), 7.45-7.18 (m, 6H), 7.04 (d, J = 8.0 Hz, 2H), 6.98 (d, J = 8.0 Hz, 2H), 6.68 (d, J = 6.4 Hz, 2H), 5.88
ddd, J = 16.8, 10.4, 4.8 Hz, 1H), 5.01 (d, J = 10.4 Hz, 1H), 4.94 (dd, J = 17.2, 1.6 Hz, 1H), 4.05-3.85 (m,
(
3H), 3.50 (quint, J = 5.6 Hz, 1H), 2.98 (dd, J = 16.0, 5.2 Hz, 1H), 2.83 (dd, J = 16.0, 10.0 Hz, 1H), 2.80-2.75
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The Journal of Organic Chemistry
1
3
1
(
m, 1H), 1.21 (d, J = 1.6 Hz, 3H), 1.19 (d, J = 6.4 Hz, 3H), 1.03 (t, J = 7.2 Hz, 3H). C{ H} NMR (100 MHz,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
CDCl ):  172.9, 168.1, 146.9, 139.5, 139.0, 138.9, 136.5, 130.0, 128.5 (2C), 128.2 (2C), 127.98 (3C),
3
1
27.96 (2C), 127.1 (2C), 126.0 (2C), 115.4, 69.3, 60.0, 47.5, 36.0, 33.6, 24.04, 23.95, 13.9. HRMS (ESI-
+
TOF) m/z: [M+H] Calcd for C H NO 440.2590; Found: 440.2589.
30 34
2
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
CF3
O
OEt
N
Ph
Ph 7g
Ethyl 4-((diphenylmethylene)amino)-3-(4-(trifluoromethyl)phenyl)hex-5-enoate (7g): Following the
general procedure, addition of lithium anion of 1 (0.2 g, 0.9 mmol) to ethyl (E)-3-(4-
(trifluoromethyl)phenyl)acrylate (0.146 g, 0.6 mmol) furnished 7g (0.118 g, 42%) as a colorless oil. Rf

1 1
0
.5 (Petroleum ether/EtOAc, 9.5:0.5). IR (Neat): max 3396, 2928, 1734, 1621, 1326, 1120 cm . H NMR
(
400 MHz, CDCl ):  7.64 (d, J = 7.6 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.43-7.26 (m, 6H), 7.19 (d, J = 8.0
3
Hz, 2H), 6.71 (d, J = 6.8 Hz, 2H), 5.86 (ddd, J = 17.2, 10.4, 5.6 Hz, 1H), 5.04 (d, J = 10.4 Hz, 1H), 4.93 (d, J
= 17.2 Hz, 1H), 3.95 (q, J = 7.2 Hz, 3H), 3.58 (quint, J = 5.2 Hz, 1H), 3.01 (dd, J = 16.0, 4.8 Hz, 1H), 2.88
1
3
1
(
dd, J = 16.0, 10.4 Hz, 1H), 1.06 (t, J = 7.2 Hz, 3H). C{ H} NMR (125 MHz, CDCl ):  172.4, 168.7, 146.1,
3
139.3, 138.2, 136.3, 130.3, 128.9 (q, J = 32.1 Hz), 128.8 (2C), 128.5 (2C), 128.3, 128.2 (2C), 128.1 (2C),
C-F
1
27.1 (2C), 125.0 (q, JC-F = 3.8 Hz, 2C), 124.2 (q, JC-F = 270.3 Hz), 116.2, 69.0, 60.3, 47.8, 35.6, 14.0.
+
HRMS (ESI-TOF) m/z: [M+Na] Calcd for C H F NO Na 488.1813; Found: 488.1816.
2
8
26 3
2
OMe
O
OEt
N
Ph
Ph 7h
Ethyl 4-((diphenylmethylene)amino)-3-(3-methoxyphenyl)hex-5-enoate (7h): Following the general
procedure, addition of lithium anion of 1 (0.2 g, 0.9 mmol) to ethyl (E)-3-(3-methoxyphenyl)acrylate
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(
0.124 g, 0.6 mmol) furnished 7h (0.141 g, 55%) and 8h (10 mg, 4%) as a colorless oil. 7h: R 0.6
f
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6

1 1
(Petroleum ether/EtOAc, 9:1). IR (Neat): max 3400, 2927, 1732, 1597, 1255, 1031 cm . H NMR (400
MHz, CDCl ):  7.66 (dt, J = 6.8, 2.0 Hz, 2H), 7.44-7.26 (m, 6H), 7.10 (t, J = 8.0 Hz, 1H), 6.76 (d, J = 6.4 Hz,
3
2
1
H), 6.69 (td, J = 8.8, 2.0 Hz, 2H), 6.65-6.58 (m, 1H), 5.87 (ddd, J = 17.2, 10.4, 5.2 Hz, 1H), 5.01 (dt, J =
0.4, 1.6 Hz, 1H), 4.92 (dt, J = 17.2, 1.6 Hz, 1H), 3.99 (bs, 1H), 3.95 (q, J = 7.2 Hz, 2H), 3.64 (bs, 3H), 3.51
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(quint, J = 5.2 Hz, 1H), 2.96 (dd, J = 16.0, 5.2 Hz, 1H), 2.81 (dd, J = 16.0, 10.0 Hz, 1H), 1.06 (t, J = 7.2 Hz,
13
1
3
1
H). C{ H} NMR (100 MHz, CDCl ):  172.7, 168.3, 159.2, 143.3, 139.4, 138.6, 136.4, 130.0, 128.9,
3
28.4 (2C), 128.10, 128.05 (2C), 128.0 (2C), 127.2 (2C), 120.8, 115.6, 113.8, 112.1, 69.1, 60.1, 54.9,
+
47.9, 36.2, 14.0. HRMS (ESI-TOF) m/z: [M+H] Calcd for C H NO 428.2226; Found: 428.2227.
2
8
30
3
OMe
O
OEt
Ph
N
Ph
8h
Ethyl (Z)-6-((diphenylmethylene)amino)-3-(3-methoxyphenyl)hex-5-enoate (8h): R 0.5 (Petroleum
f

1 1
ether/EtOAc, 9:1). IR (Neat): max 3393, 2927, 1731, 1595, 1219, 1027 cm . H NMR (400 MHz, CDCl ):
3

7.63 (dd, J = 8.4, 1.2 Hz, 2H), 7.50-7.41 (m, 3H), 7.40-7.30 (m, 3H), 7.21 (t, J = 7.6 Hz, 1H), 7.15-7.05
(m, 2H), 6.82-6.70 (m, 3H), 6.68 (d, J = 13.2 Hz, 1H), 6.07 (dt, J = 13.2, 7.6 Hz, 1H), 4.04 (q, J = 7.2 Hz,
2
1
1
H), 3.79 (s, 3H), 3.23 (quint, J = 7.2 Hz, 1H), 2.67 (dd, J = 15.2, 6.8 Hz, 1H), 2.56 (dd, J = 15.2, 8.4 Hz,
1
3
1
H), 2.42 (t, J = 7.6 Hz, 2H), 1.14 (t, J = 7.2 Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  172.1, 165.5,
3
59.6, 145.1, 139.7, 139.6, 136.2, 130.3, 130.1, 129.3, 128.8 (2C), 128.7 (2C), 128.6, 128.3 (2C), 128.0
+
(2C), 119.9, 113.2, 111.8, 60.2, 55.1, 42.2, 40.7, 37.2, 14.1. HRMS (ESI-TOF) m/z: [M+Na] Calcd for
C H NO Na 450.2045; Found: 450.2047.
2
8
29
3
Me
O
OEt
N
Ph
Ph 7i
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The Journal of Organic Chemistry
Ethyl 4-((diphenylmethylene)amino)-3-(o-tolyl)hex-5-enoate (7i): Following the general procedure,
addition of lithium anion of 1 (0.2 g, 0.9 mmol) to ethyl (E)-3-(o-tolyl)acrylate (0.114 g, 0.6 mmol)
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
furnished 7i (0.125 g, 51%) as a colorless solid and 8i (39 mg, 16%) as a colorless oil. 7i : R 0.6
f

1
(
Petroleum ether/EtOAc, 9.5:0.5). mp 86-90 °C. IR (KBr): max 2980, 1730, 1623, 1285, 1024, 763 cm .
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
H NMR (400 MHz, CDCl ):  7.66 (d, J = 7.2 Hz, 2H), 7.45-7.25 (m, 6H), 7.15-6.90 (m, 4H), 6.71 (d, J =
3
6
1
.8 Hz, 2H), 5.86 (ddd, J = 17.2, 10.4, 5.2 Hz, 1H), 4.98 (dd, J = 10.8, 1.6 Hz, 1H), 4.90 (d, J = 17.2 Hz,
H), 4.10-3.80 (m, 4H), 2.98 (dd, J = 15.6, 5.2 Hz, 1H), 2.82 (dd, J = 15.6, 10.0 Hz, 1H), 2.25 (s, 3H), 1.01
1
3
1
(
t, J = 7.2 Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  172.8, 168.4, 139.8, 139.4, 138.5, 136.7, 136.5,
3
130.1, 130.0, 128.5 (2C), 128.1, 128.0 (2C), 127.95 (2C), 127.1 (2C), 126.7, 126.0, 125.5, 115.4, 68.4,
+
6
0.0, 42.5, 36.4, 19.8, 13.9. HRMS (ESI-TOF) m/z: [M+H] Calcd for C H NO 412.2277; Found:
2
8
30
2
412.2278.
Me
O
OEt
Ph
N
Ph
8i
Ethyl (Z)-6-((diphenylmethylene)amino)-3-(o-tolyl)hex-5-enoate (8i): R 0.5 (Petroleum ether/EtOAc,
f
1
1
9
.5:0.5). IR (Neat): max 3399, 2926, 1732, 1660, 1276, 1026 cm . H NMR (400 MHz, CDCl ):  7.61 (d,
3
J = 7.2 Hz, 2H), 7.45-7.38 (m, 2H), 7.38-7.25 (m, 4H), 7.20-7.02 (m, 6H), 6.64 (d, J = 13.2 Hz, 1H), 6.05
(dt, J = 12.8, 8.0 Hz, 1H), 3.99 (q, J = 7.2 Hz, 2H), 3.55 (quint, J = 8.0 Hz, 1H), 2.66 (dd, J = 15.2, 6.8 Hz,
1
3
1
1
H), 2.52 (dd, J = 15.6, 8.4 Hz, 1H), 2.50-2.28 (m, 5H), 1.09 (t, J = 7.2 Hz, 3H). C{ H} NMR (100 MHz,
CDCl ):  172.3, 165.5, 141.6, 139.7, 139.6, 136.2, 135.9, 130.3, 130.2, 130.1, 128.8 (2C), 128.7 (2C),
3
1
28.6, 128.3 (2C), 128.0 (2C), 126.1, 126.0, 125.6, 60.2, 40.2, 37.0, 36.7, 19.7, 14.0. HRMS (ESI-TOF)
+
m/z: [M+H] Calcd for C H NO 412.2277; Found: 412.2275.
2
8
30
2
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1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Br
O
OEt
N
Ph
Ph 7j
Ethyl 3-(2-bromophenyl)-4-((diphenylmethylene)amino)hex-5-enoate (7j): Following the general
procedure, addition of lithium anion of 1 (0.2 g, 0.9 mmol) to ethyl (E)-3-(2-bromophenyl)acrylate
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(
0.152 g, 0.6 mmol) furnished 7j (0.101 g, 35%) as a brown solid and 8j (0.122 g, 43%) as a colorless oil.
7
j: R 0.6 (Petroleum ether/EtOAc, 9.5:0.5). mp 75-80 °C. IR (KBr):  3431, 2921, 1624, 1246, 1023
f
max
1
1
cm . H NMR (400 MHz, CDCl ):  7.63 (d, J = 7.6 Hz, 2H), 7.46 (d, J = 7.2 Hz, 1H), 7.45-7.30 (m, 5H),
3
7
1
.30-7.20 (m, 2H), 7.20-7.05 (m, 2H), 7.00 (td, J = 8.8, 2.0 Hz, 1H), 6.53 (d, J = 5.6 Hz, 1H), 6.00 (ddd, J =
7.2, 10.4, 5.2 Hz, 1H), 5.06 (d, J = 10.4 Hz, 1H), 4.98 (d, J = 17.2 Hz, 1H), 4.20-4.02 (m, 2H), 4.02-3.90
1
3
1
(
m, 2H), 3.12-2.98 (m, 2H), 1.06 (t, J = 7.2 Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  172.5, 168.8, 140.5,
3
139.3, 138.4, 136.3, 132.8, 130.0, 128.5 (2C), 128.1, 128.0 (3C), 127.96 (3C), 127.7, 126.9 (2C), 126.86,
+
1
15.8, 66.9, 60.2, 45.8, 34.6, 14.0. HRMS (ESI-TOF) m/z: [M+Na] Calcd for C H BrNO Na 498.1045;
2
7
26
2
Found: 498.1043.
Br
O
OEt
Ph
N
Ph
8j
Ethyl (Z)-3-(2-bromophenyl)-6-((diphenylmethylene)amino)hex-5-enoate (8j): R 0.5 (Petroleum
f

1 1
ether/EtOAc, 9.5:0.5). IR (Neat): max 3427, 2925, 1731, 1658, 1276, 1024 cm . H NMR (400 MHz,
CDCl ):  7.62 (d, J = 7.6 Hz, 2H), 7.53 (d, J = 8.0 Hz, 1H), 7.48-7.38 (m, 3H), 7.38-7.28 (m, 3H), 7.24 (t, J
3
=
7.6 Hz, 1H), 7.16 (dd, J = 8.0, 1.6 Hz, 1H), 7.13-7.02 (m, 3H), 6.67 (d, J = 13.2 Hz, 1H), 6.08 (dt, J = 12.8,
8.0 Hz, 1H), 4.01 (q, J = 7.2 Hz, 2H), 3.84 (quint, J = 7.6 Hz, 1H), 2.68 (dd, J = 15.6, 7.2 Hz, 1H), 2.61 (dd, J
1
3
1
=
15.6, 8.4 Hz, 1H), 2.55-2.32 (m, 2H), 1.11 (t, J = 7.2 Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  171.6,
3
165.6, 142.0, 140.0, 139.4, 136.1, 133.0, 130.1, 129.4, 128.7 (4C), 128.6, 128.3 (2C), 128.0 (2C), 127.8,
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The Journal of Organic Chemistry
+
1
4
27.7, 127.4, 124.9, 60.3, 40.2, 39.1, 35.8, 14.0. HRMS (ESI-TOF) m/z: [M+H] Calcd for C H BrNO
2
7
27
2
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
76.1225; Found: 476.1225.
OMe
MeO
OMe
O
OEt
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
N
Ph
Ph 7K
Ethyl 4-((diphenylmethylene)amino)-3-(3,4,5-trimethoxyphenyl)hex-5-enoate (7k): Following the
general procedure, addition of lithium anion of 1 (0.2 g, 0.9 mmol) to ethyl (E)-3-(3,4,5-
trimethoxyphenyl)acrylate (0.160 g, 0.6 mmol) furnished 7k (0.159 g, 54% [71% brsm]) as a colorless

1 1
oil. R 0.4 (Petroleum ether/EtOAc, 8:2). IR (Neat):  2934, 1732, 1588, 1422, 1242, 1126 cm . H
f
max
NMR (400 MHz, CDCl ):  7.66 (dd, J = 8.4, 1.2 Hz, 2H), 7.42-7.22 (m, 6H), 6.60 (d, J = 6.4 Hz, 2H), 6.29
3
(
bs, 2H), 5.95 (ddd, J = 17.2, 10.4, 4.8 Hz, 1H), 5.10 (dd, J = 10.8, 1.6 Hz, 1H), 5.03 (dd, J = 17.2, 1.6 Hz,
1
3
H), 4.01 (q, J = 7.2 Hz, 2H), 4.00-3.95 (m, 1H), 3.80 (bs, 3H), 3.63 (bs, 6H), 3.44 (quint, J = 5.2 Hz, 1H),
1
3
1
.05 (dd, J = 16.0, 5.2 Hz, 1H), 2.97 (dd, J = 16.0, 10.4 Hz, 1H), 1.11 (t, J = 7.2 Hz, 3H). C{ H} NMR (100
MHz, CDCl ):  172.9, 168.2, 152.6 (2C), 139.2, 138.6, 137.6, 136.3, 136.2, 130.0, 128.3 (2C), 128.0,
3
1
27.9 (2C), 127.8 (2C), 127.0 (2C), 115.6, 105.2 (2C), 68.8, 60.7, 60.1, 55.7 (2C), 47.8, 34.9, 14.0. HRMS
+
(ESI-TOF) m/z: [M+H] Calcd for C H NO 488.2437; Found: 488.2434.
3
0
34
5
O
N
O
OEt
Ph
Ph 7l
Ethyl 4-((diphenylmethylene)amino)-3-(furan-2-yl)hex-5-enoate (7l): Following the general
procedure, addition of lithium anion of 1 (0.2 g, 0.9 mmol) to ethyl (E)-3-(furan-2-yl)acrylate (0.100 g,
0
.6 mmol) furnished 7l (0.12 g, 51%) and 8l (26 mg, 11%) as a colorless oil. 7l: R 0.5 (Petroleum
f
1
1
ether/EtOAc, 9:1). IR (Neat): max 3018, 1728, 1622, 1442, 1215, 1020 cm . H NMR (400 MHz, CDCl ):
3
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
7.62 (d, J = 5.2 Hz, 2H), 7.42-7.25 (m, 6H), 7.24-7.18 (m, 1H), 6.96-6.85 (m, 2H), 6.20 (dd, J = 3.2, 2.0
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Hz, 1H), 6.01 (d, J = 3.2 Hz, 1H), 5.92 (ddd, J = 17.2, 10.4, 5.6 Hz, 1H), 5.07 (dt, J = 10.8, 1.6 Hz, 1H), 4.97
(dt, J = 17.2, 1.6 Hz, 1H), 4.13 (tt, J = 5.6, 1.2 Hz, 1H), 4.02 (q, J = 7.2 Hz, 2H), 3.63 (quint, J = 5.2 Hz, 1H),
1
3
1
2
.90 (dd, J = 15.6, 4.8 Hz, 1H), 2.80 (dd, J = 16.0, 10.0 Hz, 1H), 1.13 (t, J = 7.2 Hz, 3H). C{ H} NMR (100
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
MHz, CDCl ):  172.5, 168.6, 155.1, 140.9 (2C), 139.5, 136.4, 130.0, 128.5 (2C), 128.3, 128.1 (2C), 127.9
3
+
(2C), 127.3 (2C), 115.9, 109.9, 106.2, 67.1, 60.2, 41.6, 34.6, 14.0. HRMS (ESI-TOF) m/z: [M+Na] Calcd
for C H NO Na 410.1732; Found: 410.1734.
2
5
25
3
O
O
OEt
Ph
N
Ph
8l
Ethyl (Z)-6-((diphenylmethylene)amino)-3-(furan-2-yl)hex-5-enoate (8l): Rf 0.4 (Petroleum
1
1
ether/EtOAc, 9:1). IR (Neat): max 3427, 2979, 1733, 1624, 1595, 1154 cm . H NMR (400 MHz, CDCl ):
3

7.63 (dd, J = 8.4, 1.6 Hz, 2H), 7.45 (dd, J = 5.2, 4.8 Hz, 2H), 7.42-7.28 (m, 5H), 7.18-7.12 (m, 2H), 6.71
(d, J = 13.2 Hz, 1H), 6.26 (dd, J = 3.2, 2.0 Hz, 1H), 6.08 (dd, J = 12.8, 6.4 Hz, 1H), 6.02 (d, J = 3.2 Hz, 1H),
4
2
1
.07 (q, J = 7.2 Hz, 2H), 3.37 (quint, J = 7.2 Hz, 1H), 2.60 (d, J = 7.6 Hz, 2H), 2.49 (sextet, J = 6.4 Hz, 1H),
1
3
1
.40 (sextet, J = 7.6 Hz, 1H), 1.18 (t, J = 7.2 Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  171.9, 165.7,
3
56.3, 141.1, 139.9, 139.5, 136.2, 130.2, 129.7, 128.8 (2C), 128.72 (2C), 128.65, 128.4 (2C), 128.1 (2C),
+
109.9, 105.4, 60.4, 38.0, 35.5, 34.5, 14.1. HRMS (ESI-TOF) m/z: [M+Na] Calcd for C H NO Na
2
5
25
3
4
10.1732; Found: 410.1730.
Cl
N
O
OEt
N
Ph
Ph 7m
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The Journal of Organic Chemistry
Ethyl 3-(6-chloropyridin-3-yl)-4-((diphenylmethylene)amino)hex-5-enoate (7m): Following the
general procedure, addition of lithium anion of 1 (0.378 g, 1.71 mmol) to ethyl (E)-3-(3-
methoxyphenyl)acrylate (0.300 g, 1.42 mmol) furnished 7m (0.342 g, 56% major), 7m’ (26 mg, 4%
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
minor) and 8m (40 mg, 7%) as a colorless oil. 7m major isomer: R 0.4 (Petroleum ether/EtOAc, 9:1). IR
f
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1 1
(
Neat): max 3382, 2924, 1731, 1619, 1582, 1455 cm . H NMR (400 MHz, CDCl ):  8.15 (bs, 1H), 7.64
3
(d, J = 7.6 Hz, 2H), 7.50-7.30 (m, 7H), 7.17 (d, J = 8.0 Hz, 1H), 6.82 (d, J = 5.6 Hz, 2H), 5.83 (ddd, J = 16.8,
10.4, 6.0 Hz, 1H), 5.07 (d, J = 10.4 Hz, 1H), 4.90 (d, J = 17.2 Hz, 1H), 4.06-3.88 (m, 3H), 3.51 (quint, J =
5
.2 Hz, 1H), 3.00 (dd, J = 16.0, 4.4 Hz, 1H), 2.82 (dd, J = 16.0, 10.4 Hz, 1H), 1.09 (t, J = 7.2 Hz, 3H).
1
3
1
C{ H} NMR (100 MHz, CDCl ):  172.0, 169.0, 149.8, 149.5, 139.0, 138.7, 137.6, 136.2, 136.1, 130.4,
3
1
28.5 (2C), 128.4, 128.3 (2C), 128.1 (2C), 127.0 (2C), 123.5, 116.8, 68.7, 60.5, 44.7, 35.5, 14.0. HRMS
+
(ESI-TOF) m/z: [M+H] Calcd for C H ClN O 433.1683; Found: 433.1681.
2
6
26
2 2
Cl
N
N
O
OEt
Ph
Ph 7m'
Ethyl 3-(6-chloropyridin-3-yl)-4-((diphenylmethylene)amino)hex-5-enoate (7m’ minor isomer): R 0.3
f

1 1
(Petroleum ether/EtOAc, 9:1). IR (Neat): max 2926, 1731, 1621, 1455, 1283, 1105 cm . H NMR (400
MHz, CDCl ):  8.27 (bs, 1H), 7.68-7.45 (m, 4H), 7.43-7.20 (m, 6H), 6.96 (d, J = 2.8 Hz, 2H), 5.82 (ddd, J =
3
17.2, 9.6, 7.6 Hz, 1H), 5.08 (d, J = 10.4 Hz, 1H), 4.92 (d, J = 17.2 Hz, 1H), 4.02 (t, J = 6.4 Hz, 1H), 3.96 (q, J
=
7.2 Hz, 2H), 3.55-3.40 (m, 1H), 2.78 (dd, J = 16.0, 5.2 Hz, 1H), 2.55 (dd, J = 16.0, 10.0 Hz, 1H), 1.10 (t, J
1
3
1
= 7.2 Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  171.5, 168.7, 150.3, 149.5, 139.4, 139.3, 137.7, 136.3,
3
1
3
35.5, 130.3, 130.0, 128.6, 128.4, 128.3 (2C), 128.2, 128.1 (2C), 127.5, 123.3, 116.8, 68.8, 60.5, 44.7,
+
7.1, 14.0. HRMS (ESI-TOF) m/z: [M+Na] Calcd for C H ClN O Na 455.1502; Found: 455.1505.
26 25
2 2
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Cl
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
N
O
OEt
Ph
N
Ph
8m
Ethyl (Z)-3-(6-chloropyridin-3-yl)-6-((diphenylmethylene)amino)hex-5-enoate (8m): R 0.2 (Petroleum
f
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0

1 1
ether/EtOAc, 9:1). IR (Neat): max 2926, 1730, 1658, 1455, 1278, 1105 cm . H NMR (400 MHz, CDCl ):
3

6
1
3
8.21 (bs, 1H), 7.61 (d, J = 7.2 Hz, 2H), 7.55-7.40 (m, 2H), 7.40-7.18 (m, 6H), 7.05 (d, J = 4.8 Hz, 2H),
.58 (d, J = 12.8 Hz, 1H), 6.00 (dt, J = 13.2, 7.6 Hz, 1H), 4.03 (q, J = 8.0 Hz, 2H), 3.26 (quint, J = 7.6 Hz,
H), 2.72 (dd, J = 15.6, 6.0 Hz, 1H), 2.54 (dd, J = 15.6, 9.2 Hz, 1H), 2.48-2.30 (m, 2H), 1.14 (t, J = 7.2 Hz,
1
3
1
H). C{ H} NMR (100 MHz, CDCl ):  171.3, 166.4, 149.6, 149.2, 140.5, 139.3, 137.9, 137.6, 136.0,
3
130.3, 130.0, 128.8 (2C), 128.6 (2C), 128.4 (2C), 128.2, 128.1 (2C), 123.9, 60.6, 40.0, 39.0, 36.8, 14.0.
+
HRMS (ESI-TOF) m/z: [M+H] Calcd for C H ClN O 433.1683; Found: 433.1685.
2
6
26
2 2
Me
O
OEt
N
Ph
Ph 7n
Ethyl 4-((diphenylmethylene)amino)-3-methylhex-5-enoate (7n): Following the general procedure,
addition of lithium anion of 1 (0.2 g, 0.9 mmol) to ethyl (E)-3-(6-chloropyridin-3-yl)acrylate (68 mg, 0.6
mmol) furnished 7n (97 mg, 49%) as a colorless oil. R 0.4 (Petroleum ether/Et O, 9.5:0.5). IR (Neat):
f
2

1 1
max 3399, 2975, 1732, 1623, 1177, 1028 cm . H NMR (400 MHz, CDCl ):  7.64 (d, J = 7.6 Hz, 2H),
3
7
5
.48-7.38 (m, 3H), 7.39-7.28 (m, 3H), 7.14 (dd, J = 5.2, 1.6 Hz, 2H), 5.94 (ddd, J = 16.8, 10.4, 6.0 Hz, 1H),
.08 (d, J = 10.4 Hz, 1H), 4.94 (d, J = 17.2 Hz, 1H), 4.06 (q, J = 7.2 Hz, 2H), 3.67 (t, J = 6.0 Hz, 1H), 2.58
(dd, J = 15.2, 4.4 Hz, 1H), 2.40-2.24 (m, 1H), 2.16 (dd, J = 15.2, 9.6 Hz, 1H), 1.19 (t, J = 7.2 Hz, 3H), 0.91
1
3
1
(
d, J = 6.8 Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  173.6, 167.7, 139.7, 138.9, 136.8, 129.9, 128.5 (2C),
3
128.2 (3C), 127.9 (2C), 127.6 (2C), 115.7, 69.6, 60.1, 37.9, 36.0, 17.0, 14.1. HRMS (ESI-TOF) m/z: [M+H]+
Calcd for C H NO 336.1964; Found: 336.1961.
2
2
26
2
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Page 25 of 42
The Journal of Organic Chemistry
O
1
2
3
4
5
6
OEt
N
Ph
Ph 7o
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
Ethyl 3-(1-((diphenylmethylene)amino)allyl)hept-6-enoate (7o): Following the general procedure,
addition of lithium anion of 1 (0.2 g, 0.9 mmol) to ethyl 3-(1-((diphenylmethylene)amino)allyl)hept-6-
enoate (92 mg, 0.6 mmol) furnished 7o (0.129 g, 58%) as a colorless oil. R 0.6 (Petroleum ether/Et O,
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
f
2

1 1
9
.5:0.5). IR (Neat): max 3070, 2924, 1732, 1624, 1280, 1166 cm . H NMR (400 MHz, CDCl ):  7.64 (d,
3
J = 7.6 Hz, 2H), 7.45-7.36 (m, 3H), 7.36-7.26 (m, 3H), 7.15 (dd, J = 7.6, 4.0 Hz, 2H), 5.93 (ddd, J = 17.2,
0.8, 5.2 Hz, 1H), 5.80-5.64 (m, 1H), 5.11 (d, J = 10.8 Hz, 1H), 4.97 (d, J = 17.6 Hz, 1H), 4.91 (d, J = 4.4
Hz, 1H), 4.86 (bs, 1H), 4.06 (q, J = 7.2 Hz, 2H), 3.90 (t, J = 5.2 Hz, 1H), 2.69 (dd, J = 16.0, 5.2 Hz, 1H), 2.39
1
(dd, J = 16.0, 8.0 Hz, 1H), 2.26-2.14 (m, 1H), 1.87 (q, J = 7.6 Hz, 2H), 1.42 (sextet, J = 7.6 Hz, 1H), 1.34
1
3
1
(
sextet, J = 8.0 Hz, 1H), 1.19 (d, J = 7.2 Hz, 3H). C{ H} NMR (100 MHz, CDCl ):  173.9, 167.9, 139.8,
3
1
6
39.4, 138.4, 137.5, 136.6, 132.4, 130.0, 129.9, 128.5, 128.4, 128.2, 128.15, 127.9, 127.6, 115.6, 114.4,
+
6.3, 60.1, 40.4, 35.6, 31.1, 30.9, 14.1. HRMS (ESI-TOF) m/z: [M+H] Calcd for C H NO 376.2277;
2
5
30
2
Found: 376.2279.
O
O
O
N
O
O
Bn
9a
(S,E)-3-(3-(benzo[d][1,3]dioxol-5-yl)acryloyl)-4-benzyloxazolidin-2-one (9a): In a 50 mL two-neck
round bottom flask equipped with argon balloon was placed a solution of diethyl (S)-(2-(4-benzyl-2-
oxooxazolidin-3-yl)-2-oxoethyl)phosphonate (0.283 g, 0.80 mmol) in CH CN (6 mL). Cs CO (0.52 g, 1.6
3
2
3
mmol) was introduced into the flask all at once and was stirred for 45 min at room temperature. The
reaction mixture was then cooled to 0°C and a solution of the 3,4-methylenedioxy benzaldehyde
(
0.110 g, 0.73 mmol) in CH CN (4 mL) was added dropwise. The reaction mixture was slowly warmed
3
up to room temperature and stirred at room temperature for 2.5 h. After completion of the reaction
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(
TLC), the reaction mixture was cautiously quenched by addition of aqueous solution of citric acid (5
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
mL), poured into water (10 mL) and extracted with EtOAc (2 × 10 mL). The combined organic layers
were washed with brine (5 mL) and dried over anhydrous Na SO . Evaporation of solvent gave the
2
4
crude residue, which was purified on silica gel column chromatography using petroleum ether/EtOAc
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(9:1) as eluent to furnish 9a (0.124 g, 48%) as a colorless solid. R 0.3 (Petroleum ether/EtOAc, 9:1).
f
2
4
1 1
[
] +42.7 (c 1.0, CHCl ). mp 129-133 °C. IR (KBr):  2917, 1776, 1669, 1613, 1341, 1206 cm . H
D
3
max
NMR (400 MHz, CDCl ):  7.75 (d, J = 15.6 Hz, 1H), 7.68 (d, J = 15.6 Hz, 1H), 7.35-7.23 (m, 2H), 7.23-7.13
3
(m, 3H), 7.09 (d, J = 1.2 Hz, 1H), 7.04 (dd, J = 8.0, 1.6 Hz, 1H), 6.75 (d, J = 8.0 Hz, 1H), 5.94 (s, 2H), 4.80-
4.65 (m, 1H), 4.16 (q, J = 9.2 Hz, 1H), 4.12 (dd, J = 9.2, 3.2 Hz, 1H), 3.29 (dd, J = 13.6, 3.2 Hz, 1H), 2.77
1
3
1
(dd, J = 13.6, 9.6 Hz, 1H). C{ H} NMR (100 MHz, CDCl ):  165.3, 153.6, 150.0, 148.4, 146.2, 135.4,
3
129.5 (2C), 129.0, 128.9 (2C), 127.3, 125.3, 114.9, 108.5, 107.0, 101.6, 66.1, 55.4, 37.9. HRMS (ESI-TOF)
+
m/z: [M+Na] Calcd for C H NO Na 374.1004; Found: 374.1003.
2
0
17
5
O
O
N
O
Cl
N
Bn
9b
(
S,E)-4-benzyl-3-(3-(6-chloropyridin-3-yl)acryloyl)oxazolidin-2-one (9b): Compound 9b was prepared
17
24
according to the procedure described by Evans et al. R 0.3 (Petroleum ether/EtOAc, 8:2). [] +77.4
f
D
1
7
24
17
1
(c 1.2, CH Cl ), Lit [] −81.4 (c 1.22, CH Cl ). mp 153-156 °C, Lit mp 144 °C. H NMR (400 MHz,
2
2
D
2
2
CDCl ):  8.56 (d, J = 2.0 Hz, 1H), 8.03-7.90 (m, 2H), 7.83 (d, J = 16.0 Hz, 1H), 7.35 (q, J = 7.2 Hz, 3H),
3
7
9
.31 (d, J = 10.4 Hz, 1H), 7.23 (d, J = 8.5 Hz, 2H), 4.87-4.73 (m, 1H), 4.27 (q, J = 9.2 Hz, 1H), 4.23 (dd, J =
1
3
1
.2, 3.2 Hz, 1H), 3.36 (dd, J = 13.6, 3.2 Hz, 1H), 2.86 (dd, J = 13.6, 9.6 Hz, 1H). C{ H} NMR (100 MHz,
CDCl ):  164.2, 153.4, 153.0, 150.2, 140.7, 136.7, 135.0, 129.4, 129.3, 128.9(2C), 127.4(2C), 124.6,
3
+
119.7, 66.3, 55.3, 37.8. HRMS (ESI-TOF) m/z: [M+H] Calcd for C H ClN O 343.0849; Found:
1
8
16
2 3
3
43.0849.
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The Journal of Organic Chemistry
O
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
O
O
O
N
O
N
Ph
Bn
Ph
1
0a
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
(S)-3-((3R,4R)-3-(benzo[d][1,3]dioxol-5-yl)-4-((diphenylmethylene)amino)hex-5-enoyl)-4-
benzyloxazolidin-2-one (10a): Following the general procedure, addition of lithium anion of 1 (0.186 g,
0
.84 mmol) to (S,E)-3-(3-(benzo[d][1,3]dioxol-5-yl)acryloyl)-4-benzyloxazolidin-2-one (0.198 g, 0.56
mmol) furnished 10a (0.188 g, 58%) as a yellowish sticky solid and 10a’ (39 mg, 12%) as a yellowish
2
4
solid. 10a: R 0.4 (Petroleum ether/EtOAc, 8:2). [] +36.4 (c 1.2, CHCl ). IR (Neat):  2922, 1778,
f
D
3
max
1
1
1
699, 1491, 1245, 1038 cm . H NMR (400 MHz, CDCl ):  7.69 (d, J = 7.6 Hz, 2H), 7.41 (dd, J = 5.2, 2.0
3
Hz, 3H), 7.38-7.30 (m, 3H), 7.30-7.18 (m, 3H), 7.10-6.95 (m, 4H), 6.75-6.60 (m, 3H), 5.90 (d, J = 1.2 Hz,
1
1
H), 5.88 (d, J = 0.8 Hz, 1H), 5.80 (ddd, J = 16.8, 10.4, 5.6 Hz, 1H), 4.94 (d, J = 10.4 Hz, 1H), 4.79 (d, J =
7.2 Hz, 1H), 4.54 (tt, J = 8.8, 3.2 Hz, 1H), 4.05-3.92 (m, 2H), 3.80-3.65 (m, 2H), 3.48 (dd, J = 16.8, 6.0
Hz, 1H), 3.40 (dd, J = 16.8, 8.4 Hz, 1H), 2.98 (dd, J = 13.6, 3.2 Hz, 1H), 2.58 (dd, J = 13.6, 9.2 Hz, 1H).
1
3
1
C{ H} NMR (100 MHz, CDCl ):  172.1, 168.7, 153.4, 147.4, 146.0, 139.5, 138.3, 136.5, 135.9, 135.1,
3
130.1, 129.4 (2C), 128.8 (2C), 128.5 (2C), 128.30 (2C), 128.26, 128.0 (2C), 127.4 (2C), 127.2,
+
1
21.8,115.6, 108.9, 107.9, 100.7, 69.8, 65.7, 55.0, 47.4, 37.8, 37.5. HRMS (ESI-TOF) m/z: [M+H] Calcd
for C H N O 573.2389; Found: 573.2386.
36 33
2
5
O
O
O
O
N
O
Ph
N
Bn
Ph
10a'
(4S)-3-((Z)-3-(benzo[d][1,3]dioxol-5-yl)-6-((diphenylmethylene)amino)hex-5-enoyl)-4-
2
4
benzyloxazolidin-2-one (10a’): R 0.3 (Petroleum ether/EtOAc, 8:2). [] +15.3 (c 1.2, CHCl ). mp 155-
f
D
3

1 1
158 °C. IR (Neat): max 2924, 1779, 1699, 1490, 1241, 1038 cm . H NMR (400 MHz, CDCl ):  7.61 (d, J
3
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=
8.0 Hz, 2H), 7.55-7.42 (m, 3H), 7.40-7.20 (m, 6H), 7.11 (d, J = 6.4 Hz, 2H), 7.03 (d, J = 6.8 Hz, 2H), 6.75
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
(d, J = 10.0 Hz, 2H), 6.68 (d, J = 12.8 Hz, 2H), 6.15-6.00 (m, 1H), 5.92 (bs, 2H), 4.62 (t, J = 11.2 Hz, 1H),
4
1
1
.20-4.00 (m, 2H), 3.50-3.38 (m, 1H), 3.34 (t, J = 7.2 Hz, 1H), 3.11 (dd, J = 16.0, 5.2 Hz, 1H), 3.03 (d, J =
1
3
1
3.2 Hz, 1H), 2.61 (dd, J = 13.6, 9.6 Hz, 1H), 2.42 (t, J = 7.2 Hz, 2H). C{ H} NMR (100 MHz, CDCl ): 
3
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
71.8, 165.7, 153.3, 147.6, 146.0, 139.8, 139.5, 137.5, 136.1, 135.0, 130.4, 130.1, 129.4 (2C), 128.8
(2C), 128.78 (2C), 128.7 (2C), 128.67, 128.4 (2C), 128.1 (2C), 127.3, 120.8, 108.2, 108.1, 100.8, 65.9,
+
55.0, 41.5, 41.1, 37.7, 37.5. HRMS (ESI-TOF) m/z: [M+H] Calcd for C H N O 573.2389; Found:
3
6 33 2 5
5
73.2389.
Cl
N
O
O
N
O
N
Ph
Bn
Ph
10b
(
S)-4-benzyl-3-((3R,4R)-3-(6-chloropyridin-3-yl)-4-((diphenylmethylene)amino)hex-5-
enoyl)oxazolidin-2-one (10b): Following the general procedure, addition of lithium anion of 1 (0.111 g,
.5 mmol) to (S,E)-4-benzyl-3-(3-(6-chloropyridin-3-yl)acryloyl)oxazolidin-2-one 9b (0.143 g, 0.42
0
2
4
mmol) furnished 10b (0.139 g, 59%) as a colorless oil. R 0.3 (Petroleum ether/EtOAc, 8:2). [] +33.7
f
D

1 1
(c 1.15, CHCl ). IR (Neat):  3435, 1779, 1698, 1375, 1106 cm . H NMR (400 MHz, CDCl ):  8.21 (d,
3
max
3
J = 2.4 Hz, 1H), 7.66 (d, J = 7.6 Hz, 2H), 7.46 (dd, J = 8.4, 2.4 Hz, 1H), 7.43-7.30 (m, 6H), 7.30-7.22 (m,
3
1
3
H), 7.20 (d, J = 8.4 Hz, 1H), 7.00 (d, J = 6.8 Hz, 2H), 6.97-6.90 (m, 2H), 5.79 (ddd, J = 16.8, 10.4, 6.0 Hz,
H), 5.00 (d, J = 10.4 Hz, 1H), 4.80 (d, J = 16.8 Hz, 1H), 4.58-4.48 (m, 1H), 4.02 (dd, J = 9.2, 2.8 Hz, 1H),
.98 (t, J = 6.4 Hz, 1H), 3.86 (t, J = 8.4 Hz, 1H), 3.78-3.68 (m, 1H), 3.56 (dd, J = 17.2, 5.6 Hz, 1H), 3.49
1
3
1
(dd, J = 17.2, 8.8 Hz, 1H), 2.98 (dd, J = 13.2, 3.2 Hz, 1H), 2.58 (dd, J = 13.6, 9.2 Hz, 1H). C{ H} NMR (100
MHz, CDCl ):  171.4, 169.3, 153.4, 150.0, 149.5, 139.0, 138.9, 137.4, 136.5, 136.1, 134.9, 130.4, 129.2
3
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Page 29 of 42
The Journal of Organic Chemistry
(
3C), 128.8 (2C), 128.5 (2C), 128.4, 128.36 (2C), 128.1 (2C), 127.2, 127.1 (2C), 123.6, 69.2, 65.9, 55.0,
1
2
3
4
5
6
7
8
9
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
4
5
5
5
5
5
5
5
5
5
5
6
+
4
4.2, 37.5, 36.7. HRMS (ESI-TOF) m/z: [M+H] Calcd for C H ClN O 564.2054; Found: 564.2053.
34 31
3 3
O
O
N
O
N
Ph
Bn
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
Ph
10c
(
S)-4-benzyl-3-((3R,4R)-4-((diphenylmethylene)amino)-3-phenylhex-5-enoyl)oxazolidin-2-one (10c):
Following the general procedure, addition of lithium anion of 1 (0.2 g, 0.9 mmol) to (S)-4-benzyl-3-
cinnamoyloxazolidin-2-one (0.184 g, 0.6 mmol) furnished 10c (0.183 g, 58%) as a colorless oil. R 0.5
f
2
4
(Petroleum ether/EtOAc, 8:2). [] +17.2 (c 1.0, CHCl ). IR (Neat):  2923, 1778, 1699, 1383, 1212
D
3
max

1 1
cm . H NMR (400 MHz, CDCl ):  7.69 (d, J = 6.8 Hz, 2H), 7.28-7.45 (m, 6H), 7.28-7.20 (m, 5H), 7.16 (d,
3
J = 7.2 Hz, 3H), 6.97 (dd, J = 7.6, 1.6 Hz, 2H), 6.95-6.88 (m, 2H), 5.82 (ddd, J = 16.8, 10.4, 5.6Hz, 1H),
4
9
.93 (d, J = 10.4 Hz, 1H), 4.79 (d, J = 17.2 Hz, 1H), 4.58-4.44 (m, 1H), 4.03 (t, J = 6.8 Hz, 1H), 3.94 (dd, J =
.2, 2.8 Hz, 1H), 3.77 (quint, J = 7.2 Hz, 1H), 3.73 (t, J = 8.4 Hz, 1H), 3.53 (dd, J = 7.2, 1.6 Hz, 2H), 2.90
13
1
(dd, J = 13.6, 2.8 Hz, 1H), 2.49 (dd, J = 13.6, 9.6 Hz, 1H). C{ H} NMR (100 MHz, CDCl ):  172.3, 168.6,
3
1
53.4, 142.0, 139.5, 138.4, 136.5, 135.2, 130.1, 129.3 (2C), 128.8 (2C), 128.7 (2C), 128.5 (2C), 128.2
(2C), 128.14 (2C), 128.13 (2C), 128.0 (2C), 127.3 (2C), 127.1, 126.5, 69.6, 65.6, 55.0, 47.8, 37.4, 37.2.
+
HRMS (ESI-TOF) m/z: [M+H] Calcd for C H N O 529.2491; Found: 529.2495.
3
5 33 2 3
O
NH
11
4
-phenyl-5-vinylpyrrolidin-2-one (11): To a stirred solution of 7b (0.287 g, 0.72 mmol) in EtOH (8 mL)
were added hydroxylamine hydrochloride (60 mg, 0.86 mmol) and sodium acetate (71 mg, 0.86 mmol)
at room temperature. The reaction mixture was heated to reflux for 5 h. After completion of the
reaction (TLC), it was allowed to cool to room temperature, most of the solvent was evaporated off
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