Diastereoselective three-component synthesis of β-amino carbonyl compounds using diazo compounds, boranes, and acyl imines under catalyst-free conditions

Article abstract of DOI:10.1021/jo5003505

Diazo compounds, boranes, and acyl imines undergo a three-component Mannich condensation reaction under catalyst-free conditions to give the anti β-amino carbonyl compounds in high diastereoselectivity. The reaction tolerates a variety of functional groups, and an asymmetric variant was achieved using the (-)-phenylmenthol as chiral auxiliary in good yield and selectivity. These β-amino carbonyl compounds are valuable intermediates, which can be transformed to many potential bioactive molecules.

Full text of DOI:10.1021/jo5003505

Note
pubs.acs.org/joc
Diastereoselective Three-Component Synthesis of β‑Amino Carbonyl
Compounds Using Diazo Compounds, Boranes, and Acyl Imines
under Catalyst-Free Conditions
Yi Luan,†,‡ Jie Yu,† Xiaowei Zhang,† Scott E. Schaus,‡ and Ge Wang*,†
†School of Materials Science and Engineering, University of Science and Technology Beijing, 30 Xueyuan Road, Haidian District,
Beijing 100083, P. R. China
‡Department of Chemistry, Boston University, 24 Cummington Street, Boston, Massachusetts 02215, United States
S
* Supporting Information
ABSTRACT: Diazo compounds, boranes, and acyl imines
undergo a three-component Mannich condensation reaction
under catalyst-free conditions to give the anti β-amino
carbonyl compounds in high diastereoselectivity. The reaction
tolerates a variety of functional groups, and an asymmetric
variant was achieved using the (−)-phenylmenthol as chiral
auxiliary in good yield and selectivity. These β-amino carbonyl
compounds are valuable intermediates, which can be transformed to many potential bioactive molecules.
he development of new multicomponent coupling
Tprocesses for complex organic molecules synthesis has
attracted intense interest in recent years.1 Multicomponent
coupling processes provide novel and complex molecules with
multiple stereocenters in a single reaction vessel, which
becomes highly desirable in modern organic and medicinal
chemistry.2 Boronates and boranes can form new C−C bond
via carbon migration in the Petasis multicomponent reaction, as
well as in other organic transformations.3 A far less studied
methodology is the Hooz three-component reaction between
alkylboranes, diazo compounds, and a suitable electrophile
(Scheme 1).4
involving boranes, diazo compounds, and acyl imines, which
can be used to synthesize β-(protected amino) carbonyl
compounds under catalyst-free conditions. These β-amino
carbonyl compounds are valuable intermediates, which can be
further transformed to biologically active molecules.8
A central challenge in the development of the desired
sequential process is the reaction between the diazo substrate
and organoboron derivative to form a boron enolate.9 If a single
enolate isomer is formed, then the subsequent Mannich-type
reaction should proceed via a closed-transition state in a highly
diastereoselective manner. In a recent report by Schaus and
Luan, copper catalysts were used to develop a unique
Mannich−Hooz reaction in excellent yields but substrate-
dependent diastereoselectivity.10 It is reasoned that the use of
the Lewis acidic copper in the reaction could erode
diastereoselectivity through a number of pathways.11 Through
the use of catalyst-free conditions, we hoped to expand the
scope of the reaction and concomitantly improve the
diastereoselectivity.12
Scheme 1. Three-Component Mannich Reactions
Our investigation began with a screen of phenyl-substituted
organoboronic acids and esters as potential partners in the
reaction with α-diazoacetophenone 2a and phenyl methyl
carbamate imine 3a. When using boronic acid 1a we observed
none of the desired product, due to undesired aziridine 5
formation (Table 1, entry 1).13 Diethoxy phenyl boronate 1b
was unable to participate in this reaction under uncatalyzed
conditions (Table 1, entry 2).14 Use of electron-withdrawing
trifluoroethoxy groups on the boronates failed to increase the
yield (Table 1, entry 3). A similar low yield was also observed
with triphenylboroxine 1d (Table 1, entry 4).
Mukaiyama and co-workers applied the Hooz three-
component reaction to an aldol-type reaction of benzaldehyde.5
Miranda developed a two-step synthesis of 1,3-diketones and β-
ketoesters taking advantage of Hooz’s multicomponent
strategy, which was also employed by Wang and Barluenga.6
Dilman introduced boronic ester as the boron source in the
three-component amino ester synthesis.7 Herein, we report a
highly diastereoselective multicomponent Mannich reaction
Received: February 15, 2014
Published: April 30, 2014
© 2014 American Chemical Society
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dx.doi.org/10.1021/jo5003505 | J. Org. Chem. 2014, 79, 4694−4698

The Journal of Organic Chemistry
Note
Table 1. Optimization of the Three-Component Mannich
Reaction
Table 2. Evaluation of Borane and Diazo Components in the
Mannich Reaction
a
a
b
entry
R1
diazo (R2)
product
yield (%)
1
2
3
4
Ph
2a (Ph)
2a (Ph)
2a (Ph)
2b (OEt)
4a
4b
4c
4d
85
81
86
84
4-CH3OC6H4
4-FC6H4
Ph
b
b
entry boron
solvent
yield of 4a (%) yield of 5 (%)
dr
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
CH2Cl2
PhCH3
THF
76
a
Reactions were run with 1.2 mmol of triaryl borane 1, 1.2 mmol of
8
10
11
11
85
66
52
diazo compound 2, and 1.0 mmol of imine 3a in CH2Cl2 for 6 h under
Ar, followed by flash chromatography on silica gel. Isolated yield.
b
Table 3. Three-Component Mannich Reactions of Various
Imines
a
>20:1
>20:1
>20:1
1f
1f
a
Reactions were run with 1.2 mmol of boron 1, 1.2 mmol of diazo
ketone 2, and 1.0 mmol of acyl imine 3a in CH2Cl2 (0.2 M) for 6 h
b
under Ar, followed by flash chromatography on silica gel. Isolated
yield.
b
entry
1
R
imine
product
yield (%)
(E)-PhCHCH
3a
3b
3c
3d
3e
3f
6a
6b
6c
6d
6e
6f
85
82
89
81
81
84
A survey of B-phenyl-9-borabicyclo[3.3.1]nonane 1e resulted
in low yield, due to an undesired alkyl migration (B-Ph-9-BBN
1e, Table 1, entry 5). This B-alkyl bond migration is similar to
what Hooz and Schaus observed in previous multicomponent
Mannich reactions.10,15 To increase the specificity of the
migration, the use of triphenyl borane 1f was applied to the
reaction and gave the 85% yield under catalyst-free conditions
(Table 1, entry 6). Furthermore, the product is formed in
excellent diastereoselectivity (>20:1 dr) as the anti diaster-
eomer.16 A solvent screen showed polar, noncoordinating
CH2Cl2 gave the best results among other common organic
solvents (Table 1, entries 6−8). The optimized reaction
conditions utilized a slight excess of borane 1f and
diazoacetophenone 2a relative to the imine 3a in CH2Cl2 to
afford the desired compound in 85% yield.
With the optimal reaction conditions of commercially
available triphenyl borane 1f in hand (Table 2, entry 1), we
extended this multicomponent methodology to other boranes
and diazocarbonyl compounds. Both electron-rich and electron-
deficient triaryl boranes 1b and 1c were suitably reactived
(Table 2, entries 2 and 3), providing the desired products 4b
and 4c in 81% and 86% yield, respectively. Ethyl diazoacetate
2b was also compatible with our system, thereby accessing a β-
amino acid-type scaffold (4d, Table 2, entry 4).17 In each
instance, the newly formed products were formed in >20:1 dr.
A selection of carbamate-protected imines was tested in the
three-component reaction under the optimal conditions. The
cinnamaldehyde-derived imine 3a participated well, providing
the 1, 2-addition product in 85% yield at room temperature
(Table 3, entry 1). Electron-deficient imines 3b,c were
transformed to the desired three-component adducts in good
yields (Table 3, entries 2 and 3). Electron-rich imines 3d,e
worked smoothly, albeit under prolonged reaction time (Table
3, entries 4 and 5). 2-Naphthyl imine 3f also gave good yield
c
2
4-BrC6H4
3
3-FC6H4
d
4
d
3-CH3OC6H4
3,4-(OCH2O)C6H3
2-naphthyl
5
6
a
Reactions were run with 1.2 mmol of triphenyl borane 1a, 1.2 mmol
α-diazoacetophenone 2a, and 1.0 mmol imine 3 in CH2Cl2 for 6 h
under Ar, followed by flash chromatography on silica gel. Isolated
yield. 10% DMF as the cosolvent. 12 h.
b
c
d
with nearly exclusive anti selectivity in this three-component
process (Table 3, entry 6).
An asymmetric variant of multicomponent Mannich reaction
involving borane and diazo compounds was developed using
chiral diazoesters (Scheme 2).10,18 Several chiral diazo esters
have been evaluated. Among those investigated, the commer-
cially available (−)-phenylmenthol, which can also be
synthesized inexpensively over four steps,19 affords the chiral
8 in over 98:2 dr and 85% yield.20
Our proposed mechanism begins with the negatively
polarized α-carbon of diazo compound 2 attacking electrophilic
boron 1f. The extrusion of nitrogen and migration of phenyl
selectively affords boron (E)-enolate 9 (Figure 1). Previous
reports of boron enolate formation have shown the preferential
formation of the (E)-conformer, often with high selectivity.10,21
In agreement with these observations, calculations of the
ground-state energies of (E)-9 and (Z)-9 show the (E)-isomer
to be favorable by 2.9 kcal/mol.22 Next, the Mannich addition
to acyl imine 3 occurs through Zimmerman−Traxler transition
state to give the anti β-keto amine.
To minimize 1,3-diaxial interactions in between the bulky
aromatic groups in the transition state, we propose an (E)/(Z)-
imine isomerization occurs to form the more reactive (Z)-
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The Journal of Organic Chemistry
Note
Scheme 2. Asymmetric Multicomponent Mannich Reaction Using a Chiral Diazoester
Figure 1. Proposed mechanism for three-component Mannich reaction (hydrogen atoms are partially omitted for clarity).
140.6, 139.0, 138.6, 136.4, 130.9, 130.3, 129.9, 129.3, 128.4, 128.1,
128.1, 127. 8, 127.7, 127.6, 127.3, 66.8, 57.9, 52.5. IR (thin film, cm−1):
3421, 1718, 1653, 1486, 1453, 1242, 744, 711. HRMS (ESI-TOF) m/
z: [M + Na]+ calcd for C23H21NO3Na 382.1419, found 382.1438.
Methyl (2-(4-Methoxyphenyl)-3-oxo-1,3-diphenylpropyl)-
carbamate (Table 2, 4b). The crude mixture was purified through
flash column chromatography with elution by 98:2−95:5 hexanes/
imine. The thermodynamically less favored (Z)-conformer has
been previously proposed as an intermediate by Corey and
Schaus in reactions with sterically congested closed-transition
states.23
In conclusion, we have developed a diastereoselective three-
component reaction under catalyst-free conditions. This
reaction demonstrates a new multicomponent approach to
access various β-amino esters. The three-component reaction
was conducted asymmetrically employing the (−)-phenyl-
menthol ester in good diastereoselectivity and yield. A
transition-state calculation was performed employing B3LYP/
6-31G** set in order to reveal the mechanism of the
multicomponent reaction.
1
EtOAc. Yield: 334 mg, 81%, liquid. H NMR (CDCl3, 400 MHz): δ
7.44−6.97 (m, 11H), 6.96−6.79 (m, 2H), 6.73 (d, J = 8.9 Hz, 1H),
6.07 (s, 1H), 5.45−5.38 (m, 1H), 5.07−4.91 (m, 1H), 3.91−3.57 (s*2,
6H). 13C NMR (CDCl3, 101 MHz): δ 195.2, 158.5, 155.5, 139.1,
136.5, 132.5, 131.6, 131.1, 130.1, 129.8, 129.2, 128.5, 128.1, 128.0,
127.9, 127. 7, 127.6, 127.2, 112.9, 77.4, 77.1, 76.8, 66.8, 65.3, 55.2,
52.4. IR (thin film, cm−1): 3421, 2951, 2837, 1712, 1648, 1511, 1495,
1297, 1252, 1186, 1034, 831, 700. HRMS (ESI-TOF) m/z: [M + Na]+
calcd for C24H23NO4Na 412.1525, found 412.1514.
EXPERIMENTAL SECTION
Methyl (2-(4-Fluorophenyl)-3-oxo-1,3-diphenylpropyl)carbamate
(Table 2, 4c). The crude mixture was purified through flash column
chromatography with elution by 98:2−95:5 hexanes/EtOAc. Yield:
324 mg, 86%, liquid. IR (thin film, cm−1): 3432, 3051, 1715, 1654,
1506, 1310, 1227, 1167, 1083, 838, 755, 599. HRMS (ESI-TOF) m/z:
■
General Procedure Used for the Preparation of Amido
Ketone under Catalyst-Free Conditions (Table 1). A 10 mL
round-bottom flask was charged with a stir bar under Ar (overdried).
Triphenylborane (290 mg, 1 mmol) in 2.5 mL of dichloromethane was
added to the flask, which was then stirred at room temperature, and a
solution of the α-diazoacetophenone (175 mg, 1.2 mmol) and phenyl
methyl carbamate imine (163 mg, 1.2 mmol) in 0.5 mL of
dichloromethane was added dropwise over 5 min. The solution was
further stirred at room temperature for 12 h followed by flash
chromatography over silica gel (elution with 98:2, hexanes/EtOAc) to
afford the amido ketone 4a as a colorless oil (305 mg, 85% yield).
Methyl (3-Oxo-1,2,3-triphenylpropyl)carbamate (Table 2, 4a).
The crude mixture was purified through flash column chromatography
with elution by 98:2−95:5 hexanes/EtOAc. Yield: 305 mg, 85%, liquid.
1H NMR (CDCl3, 400 MHz): δ 7.27−6.95 (m, 13H), 6.76 (t, J = 14.5
1
[M + Na]+ calcd for C23H20NO3FNa 400.1325, found 400.1333]. H
NMR (CDCl3, 400 MHz): δ 7.27−6.77 (m, 12H), 6.73 (m, 2H), 5.92
(m, 1H), 5.35−5.26 (m, 1H), 4.83 (d, J = 12.3 Hz, 1H), 3.66−3.44 (s,
3H). 13C NMR (CDCl3, 101 MHz): δ 193.1, 162.4, 160.6, 155.5,
140.6, 138.9, 136.4, 132.2, 131.8, 130.0, 129.8, 129.2, 128.5, 128.2,
128.1, 128.1, 128.0, 127.8, 127.8, 127.7, 127.4, 114.5, 114.3, 66. 9, 65.4,
52.6.
Ethyl 3-((Methoxycarbonyl)amino)-2,3-diphenylpropanoate
(Table 2, 4d). The crude mixture was purified through flash column
chromatography with elution by 98:2−95:5 hexanes/EtOAc. Yield:
1
275 mg, 84%, liquid. H NMR (CDCl3, 300 MHz): δ 7.45−7.02 (m,
8H), 6.84 (d, J = 7.0 Hz, 2H), 6.06 (d, J = 10.1 Hz, 1H), 5.92 (d, J =
10.0 Hz, 1H), 4.24−3.89 (m, 2H), 3.72 (s, 3H), 1.16 (t, J = 7.1 Hz,
Hz, 2H), 5.98 (s, 1H), 5.42 (t, J = 15.7 Hz, 1H), 4.86 (d, J = 12.3 Hz,
1H), 3.60 (s, 3H). 13C NMR (CDCl3, 101 MHz): δ 193.2, 155.5,
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The Journal of Organic Chemistry
Note
3H). 13C NMR (CDCl3, 75 MHz): δ 192.6, 154.3, 140.7, 139.2, 130.4,
129.9, 129.2, 127. 8, 127.6, 127.5, 127.2, 65.9, 61.0, 57.7, 52.4, 14.6. IR
(thin film, cm−1): 3432, 1718, 1652, 1496, 1456, 1229, 754, 699.
HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C19H21NO4Na
350.1386, found 350.1381.
3.89−3.50 (m, 3H). 13C NMR (101 MHz, CDCl3) δ 196.6, 155.5,
140.6, 138.7, 136.5, 136.4, 132.9, 132.6, 130.5, 129.9, 128.9, 128.6,
128.2, 128.2, 128.1, 127.9, 127.9, 127.5, 127.4, 127.1, 126.9, 126.2,
125.9, 66.9, 66.0, 52.5. IR (thin film, cm−1): 3429, 3051, 1719, 1657,
1491, 1454, 1311, 1217, 1178, 1059, 741, 698. HRMS (ESI-TOF) m/
z: [M + Na]+ calcd for C27H23NO3Na 432.1576, found 432.1568].
General Procedure Used for Asymmetric Three-Component
Reaction Using Chiral Auxiliaries (Figure 1). A 10 mL round-
bottom flask was charged with a stir bar under Ar (overdried). To the
flask was added triphenylborane (290 mg, 1 mmol) in 2.5 mL of
dichloromethane. The mixture was then stirred at room temperature,
and a solution of the phenylmenthyl diazoacetate (360 mg, 1.2 mmol)
and phenyl methyl carbamate imine (163 mg, 1.2 mmol) in 0.5 mL of
dichloromethane was added dropwise over 5 min. The solution was
cooled to −10 °C for 24 h followed by flash chromatography over
silica gel (elution with 98:2−95:5 hexanes/EtOAc) to afford the chiral
carbamate 8 as a colorless oil (436 mg, 85% yield, > 98:2 dr).
(2S,3R)-(1R,2S,5R)-5-Methyl-2-(2-phenylpropan-2-yl)cyclohexyl
Methyl ((E)-5-Oxo-1,4,5-triphenylpent-1-en-3-yl)carbamate
(Table 3, 6a). The crude mixture was purified through flash column
chromatography with elution by 98:2−95:5 hexanes/EtOAc. Yield:
1
327 mg, 85%, liquid. H NMR (400 MHz, CDCl3): δ 7.56−7.09 (m,
15H), 6.38 (t, J = 21.0 Hz, 1H), 6.08 (dd, J = 15.8, 6.2 Hz, 1H), 5.90−
5.73 (m, 1H), 5.20−5.02 (m, 1H), 3.70 (s, 3H). 13C NMR (101 MHz,
CDCl3): δ 194.1, 155.6, 139.6, 136.6, 136.4, 132.6, 130.1, 129.6, 128.6,
128.5, 128.1, 128.0, 127.9, 127.7, 127.5, 127.4, 126.8, 126.5, 66. 9, 65.2,
52.6. IR (thin film, cm−1): 3424, 3041, 2941, 1721, 1643, 1493, 1442,
1307, 1229, 1042, 967, 743, 692. HRMS (ESI-TOF) m/z: [M + Na]+
calcd for C25H23NO3Na 408.1576, found 408.1567.
Methyl (1-(4-Bromophenyl)-3-oxo-2,3-diphenylpropyl)-
carbamate (Table 3, 6b). The crude mixture was purified through
flash column chromatography with elution by 98:2−95:5 hexanes/
3-((Methoxycarbonyl)amino)-2,3-diphenylpropanoate (8). Yield:
1
436 mg, 85%, liquid. dr: > 98:2. [α]23 = −32.8 (c 1.0, CHCl3). H
1
D
EtOAc. Yield: 358 mg, 82%, liquid. H NMR (400 MHz, CDCl3): δ
NMR (400 MHz, CDCl3): δ 7.57−6.96 (m, 13H), 6.76 (d, J = 7.3,
2H), 6.03 (s, 1H), 5.56 (d, 1H), 5.25(d, 1H), 4.71 (m, 1H), 4.04 (s,
3H), 1.86 (s, 1H), 1.67 (s, 1H), 1.55 (s, 1H), 1.42 (s, 2H), 1.26 (s,
4H), 0.99 (d, J = 9.5, 6H), 0.74 (m, 6H). 13C NMR (101 MHz,
CDCl3) δ 171.4, 156.0, 138.9, 137.6, 137.3, 132.1, 130.5, 129.7, 129.0,
128.5, 128.3, 128.0, 127.8, 127.6, 127.2, 126.9, 125.9, 125.5, 125.4,
122.8, 78.8, 57.4, 56.2, 51. 8, 50.5, 41.0, 40.1, 34.4, 31.3, 30.3, 27.7,
23.7, 22.7, 21.7. IR (thin film, cm−1): 3037, 2943, 1719, 1605, 1487,
1231, 758, 704. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C33H39NO4Na+ 536.2777, found 536.2780.
7.40−6.87 (m, 12H), 6.61 (d, J = 8.4 Hz, 2H), 5.93 (s, 1H), 5.46 (d, J
= 12.3 Hz, 1H), 4.86 (d, J = 12.3 Hz, 1H), 3.58 (s, 3H). 13C NMR
(101 MHz, CDCl3): δ 191.9, 154.4, 139.1, 137.2, 135.3, 130.0, 129.6,
129.1, 128.7, 127.4, 127.1, 127.0, 126.9, 126.7, 126.4, 120.7, 65.9, 64.6,
51.5. IR (thin film, cm−1): 3425, 1725, 1671, 1501, 1303, 1218, 1054,
1021, 742, 699. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for
C23H20NO3BrNa 460.0524, found 460.0517.
Methyl (1-(3-Fluorophenyl)-3-oxo-2,3-diphenylpropyl)carbamate
(Table 3, 6c). The crude mixture was purified through flash column
chromatography with elution by 98:2−95:5 hexanes/EtOAc. Yield:
1
336 mg, 89%, liquid. H NMR (400 MHz, CDCl3): δ 7.40−6.66 (m,
ASSOCIATED CONTENT
12H), 6.49 (dd, J = 23.2, 9.0 Hz, 2H), 5.96 (m, 2H), 5.43−5.34 (m,
1H), 4.87 (d, 1H), 3.55 (s, 3H). 13C NMR (101 MHz, CDCl3): δ
193.3, 155.4, 143.9, 143.7, 141.3, 141.1, 140.5, 139.1, 138.8, 130.1,
129.9, 129.2, 129.0, 128.3, 128.0, 127.7, 127.7, 127.6, 127.3, 127.0,
126.9, 125.1, 119.9, 119.9, 67.0, 65.8, 47.1. IR (thin film, cm−1): 3428,
2924, 1715, 1613, 1486, 1459, 1301, 1229, 1166, 1046, 733, 698.
HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C23H20NO3FNa
400.1325, found 400.1329.
■
S
* Supporting Information
DFT calculations and copies of 1H and 13C NMR spectra of the
products. This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*E-mail: gewang@mater.ustb.edu.cn.
■
Methyl (1-(3-Methoxyphenyl)-3-oxo-2,3-diphenylpropyl)-
carbamate (Table 3, 6d). The crude mixture was purified through
flash column chromatography with elution by 98:2−95:5 hexanes/
Notes
1
EtOAc. Yield: 315 mg, 81%, liquid. H NMR (400 MHz, CDCl3): δ
The authors declare no competing financial interest.
7.34−6.88 (m, 10H), 6.67 (dd, J = 8.2, 1.9 Hz, 1H), 6.41 (d, J = 7.8
Hz, 1H), 6.27−6.10 (m, 1H), 5.95 (t, J = 24.5 Hz, 1H), 5.42 (d, 11.3
Hz, 1H), 4.88 (d, J = 12.3 Hz, 1H), 3.63 (s, 3H), 3.53 (s, 3H). 13C
NMR (101 MHz, CDCl3): δ 197.1, 158.7, 155.5, 140.6, 140.5, 138.6,
136.4, 130.1, 129.9, 128.6, 128. 5, 128.1, 128.0, 127.8, 127.6, 127.6,
127.2, 121.4, 114.5, 113.7, 66.8, 65.8, 55.0, 52.4. IR (thin film, cm−1):
3435, 3063, 2954, 1721, 1642, 1487, 1455, 1224, 1176, 1048, 913, 731,
702. HRMS (ESI-TOF) m/z: [M + Na]+ calcd for C24H23NO4Na
412.1525, found 412.1538.
ACKNOWLEDGMENTS
■
We gratefully acknowledge Philip N. Moquist for editorial
review of the manuscript. Preliminary experiments were
performed by Y.L. at Boston University. Completion of the
work was accomplished under the direction of G.W. at the
University of Science and Technology Beijing, China. S.E.S.
and Y.L. gratefully acknowledge the NIH for support (NIGMS
R01 GM078240). Y.L., J.Y., and G.W. thank the Innovative
Foundation from China National Petroleum Corporation
(Grant No. 2012D-5006-0504) for financial support. Y.L. also
thanks the Beijing Natural Science Foundation (Grant No.
2144052) and China Postdoctoral Science Foundation
(2013M540859) for financial support.
Methyl (1-(Benzo[d][1,3]dioxol-5-yl)-3-oxo-2,3-diphenylpropyl)-
carbamate (Table 3, 6e). The crude mixture was purified through
flash column chromatography with elution by 98:2−95:5 hexanes/
1
EtOAc. Yield: 327 mg, 81%, liquid. H NMR (400 MHz, CDCl3): δ
7.32−6.89 (m, 11H), 6.49 (d, J = 8.1 Hz, 1H), 6.27 (s, 1H), 6.19 (dd, J
= 8.1, 1.5 Hz, 1H), 5.84 (m, 3H), 5.38 (t, J = 13.7 Hz, 1H), 4.88 (d, J
= 12.3 Hz, 1H), 3.63 (s, 3H). 13C NMR (400 MHz, CDCl3): δ 191.2,
155.4, 146.9, 146.9, 140.5, 138.6, 136.4, 132.8, 130.2, 129.8, 128.5,
128.1, 127.9, 127.8, 127.7, 127.6, 127.3, 123.0, 109.5, 107.4, 100.9,
66.8, 65.8, 52.5. IR (thin film, cm−1): 3431, 1721, 1657, 1493, 1429,
1311, 1221, 1035, 914, 738, 694. HRMS (ESI-TOF) m/z: [M + Na]+
calcd for C24H21NO5Na 426.1317, found 426.1322.
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