[4 + 2] Cycloaddition reactions catalyzed by a chiral oxazaborolidinium cation. Reaction rates and diastereo-, regio-, and enantioselectivity depend on whether both bonds are formed simultaneously

Article abstract of DOI:10.1021/ol100032u

chemical equation presented The reaction rates and products in enantioselective Diels-Alder reactions with a range of dienophiles correlate with the expected degree of concertedness of bond formation in the transition state.

Full text of DOI:10.1021/ol100032u

[4+2]-Cycloaddition Reactions Catalyzed by a Chiral Oxazaborolidinium
Cation. Reaction Rates, Diastereo-, Regio- and Enantioselectivity
Depend on Whether Both Bonds Are Formed Simultaneously
Santanu Mukherjee and E. J. Corey*
Department of Chemistry and Chemical Biology, Harvard University
12 Oxford St., Cambridge, MA 02138, USA
corey@chemistry.harvard.edu
SUPPORTING INFORMATION: PART A
General: Infrared (FTꢀIR) spectra were recorded on a Bruker Tensor 27, νmax in cmꢀ1. Bands are
1
characterized as broad (br), strong (s), medium (m), and weak (w). HꢀNMR spectra were recorded
on a Varian Unity INOVA 600 (600 MHz) or Varian Unity INOVA 500 (500 MHz) or a Varian
Unity INOVA 400 (400 MHz) spectrometer. Chemical shifts are reported in ppm from
tetramethylsilane with the solvent resonance as the internal standard (CDCl3: δ 7.26 ppm). Data are
reported as follows: chemical shift, multiplicity (s = singlet, d = doublet, t = triplet, q = quartet, br =
13
broad, m = multiplet), coupling constants (Hz) and integration. CꢀNMR spectra were recorded on
a Varian Unity INOVA 500 (125 MHz) spectrometer with complete proton decoupling. Chemical
shifts are reported in ppm from tetramethylsilane with the solvent resonance as the internal standard
11
(CDCl3: δ 77.00 ppm). BꢀNMR spectra were recorded on a Varian Unity INOVA 300 (96 MHz)
spectrometer with complete proton decoupling. Chemical shifts are reported in ppm from BF3ꢀEt2O
(δ 0.00 ppm). Highꢀresolution mass spectrometry was performed on either an Agilent 6210 Timeꢀ
ofꢀFlight LC/MS. Enantiomer ratios were determined by GC analysis using chiral capillary column
[J&W Scientific CyclosilꢀB column (30 m × 0.25 mm)] or HPLC analysis using chiral columns
[Chiralcel OJ and Chiralpak AD columns (25 cm × 0.46 cm)] in comparison with authentic racemic
materials.1 GCꢀanalyses were performed on HewlettꢀPackard 6850 Series GC System equipped with
flameꢀionization detector. Optical rotations were measured on a Perkin Elmer 241 Polarimeter.
Melting points were measured using a Büchi 535 Melting point apparatus. All melting points were
measured in open glass capillary and values are uncorrected.
Unless otherwise noted, all reactions have been carried out with distilled and dried solvents
under an atmosphere of dry N2 in ovenꢀ (140 oC) and flameꢀdried glassware with standard vacuumꢀ
line techniques. Toluene was purified under a positive pressure of dry argon by passage through
activated alumina columns. Dichloromethane was purified by distillation from calcium hydride
(1) Racemic DielsꢀAlder adducts were prepared either by using EtAlCl2 as catalyst (0.2 – 1.0 equiv) or without any
catalyst at rt

Mukherjee & Corey, Page S2
immediately prior to use. All workꢀup and purification procedures were carried out with reagent
grade solvents (purchased from VWR) in air. Thinꢀlayer chromatography (TLC) was performed
using E. Merck silica gel 60 F254 precoated plates (0.25 mm). Flash chromatography was performed
using Baker silica gel (40 ꢁm particle size).
• Reagents and catalysts:
Borontribromide was purchased from Aldrich and used as received.
Cyclopentadiene was isolated by thermal cracking of dicyclopentadiene and stored over 4 Å
molecular sieves at ꢀ78 ºC.
N,N´-Dicyclohexylcarbodiimide (DCC) was from Aldrich and used as received.
Diisopropylethylamine was distilled from CaH2 under a nitrogen atmosphere prior to use.
Diisopropyl-L-tartrate was purchased from Aldrich and used as received.
4-(Dimethylamino)pyridine (DMAP) was purchased from Fluka and used as received.
(S)-(-)-α,α-Diphenyl-2-pyrrolidinemethanol was purchased from Aldrich and used as received.
Ethyl chloroformate was purchased from Aldrich and used as received.
Iodine was purchased from Aldrich and used as received.
Lead tetraacetate was purchased from Aldrich and used as received.
LHMDS was purchased from Aldrich as a 1.0 M solution in THF and used as received.
Maleamic acid was purchased from Aldrich and used as received.
Maleic anhydride was purchased from Lancaster and used as received.
Methanesulfonyl chloride was purchased from Fluka and used as received.
Methylcyclopentadiene was isolated by thermal cracking of methylꢀdicyclopentadiene and stored
over 4 Å molecular sieves at ꢀ78 ºC. This is ~1:1 mixture of 1ꢀ and 2ꢀmethylcyclopentadiene.
N,N,N´,N´-Tetramethyl-L-tartaramide was purchased from Aldrich and used as received.
Triethylamine was purchased from Aldrich and distilled over CaH2 prior to use.
Triflimide was obtained from Aldrich and used as received.
2,2,2-Trifluoroethanol was purchased from Aldrich and used as received.
(Trimethylsilyl)diazomethane was purchased from Aldrich as a 2.0M solution in diethylether and
used as received.
Triphenylphosphine was purchased from Aldrich and used as received.

Mukherjee & Corey, Page S3
• Synthesis of dienophiles:
Methyl 2,2,2ꢀtrifluoroethyl fumarate (4):
Diisopropylethylamine (9.77 mL; 56.1 mmol) was added over a few min to an iceꢀcold slurry of
maleic anhydride (5.0 g; 51 mmol) in trifluoroethanol (3.67 mL; 51 mmol) in a 50 mL roundꢀ
bottom flask under positive pressure of nitrogen. After a few min the cooling bath was removed and
the resulting thick solution was stirred at room temperature for 2 h. The reaction mixture was then
acidified with 6N HCl to pH ~1 and extracted with EtOAcꢀDCM (4:1) mixture (25 mL × 5).
Combined organic layers were dried over anh. Na2SO4 and concentrated in vacuo to obtain an offꢀ
white solid (7.60 g, 38.4 mmol; 75% yield) which was used for the next step without further
purification.
S1 (3.8 g; 19.2 mmol) was placed in an ovenꢀdried 50 mL roundꢀbottom flask under
nitrogen together with 20 mL tolueneꢀMeOH (4:1) and cooled to 0 °C with an iceꢀbath. A solution
of (trimethylsilyl)diazomethane (10.0 mL of 2.0M in Et2O; 20.0 mmol) was the added over 15 min.
After stirring for further 15 min at 0 °C, the reaction mixture was allowed to warm to ambient
temperature and concentrated to obtain an yellow oil. Silica gel column chromatographic
purification (5:1 hexanes/EtOAc) afforded S2 as a colorless oil (3.5 g, 16.5 mmol; 86% yield). FT-
IR (thin film): 3014 (w), 1734 (s), 1644 (m), 1439 (m), 1415 (m), 1390 (m), 1282 (s), 1243 (w),
1150 (s), 1047 (m), 978 (m), 888 (w), 844 (w), 823 (m), 658 (m); 1H-NMR (500 MHz, CDCl3): δ
13
6.36 (d, J = 12.3 Hz; 1H), 6.27 (d, J = 12.3 Hz; 1H), 4.54 (q, J = 8.5 Hz; 2H), 3.78 (s; 3H); C-
NMR (125 MHz, CDCl3): δ 165.1, 163.4, 131.7, 127.6, 122.7 (q, J = 275 Hz), 60.8 (q, J = 36.8
Hz), 52.3.
Triphenylphosphine (247 mg; 0.943 mmol) was added to a solution of S2 (2.00 g; 9.43
mmol) in 12 mL dichloromethane at rt The resulting mixture was stirred at rt for 18 h and
concentrated in vacuo to obtain a colorless oil. Purification by silica gel column chromatography
(10:1 hexanes/EtOAc) afforded 4 as a colorless oil (1.71 g, 8.06 mmol; 85% yield). FT-IR (thin
film): 2961 (w), 1731 (s), 1649 (w), 1439 (m), 1414 (w), 1311 (s), 1274 (s), 1149 (s), 1071 (w),
1051 (m), 978 (s), 843 (w), 772 (m), 679 (w), 638 (m); 1H-NMR (500 MHz, CDCl3): δ 6.95 (d, J =
13
16.0 Hz; 1H), 6.89 (d, J = 16.0 Hz; 1H), 4.57 (q, J = 8.5 Hz; 2H), 3.82 (s; 3H); C-NMR (125
MHz, CDCl3): δ 164.8, 163.2, 135.4, 131.5, 122.7 (q, J = 275 Hz), 60.8 (q, J = 36.8 Hz), 52.4.

Mukherjee & Corey, Page S4
(E)ꢀ2,2,2ꢀTrifluoroethyl 4ꢀoxoꢀ4ꢀ(pyrrolidinꢀ1ꢀyl)butꢀ2ꢀenoate (13):
S1 (1.45 g; 7.32 mmol) was placed in a 25 mL roundꢀbottom flask together with 10 mL
dichloromethane and oxalyl chloride (1.60 mL; 18.30 mmol) was added to the solution followed by
a drop of DMF. The resulting solution was stirred at rt for 1 h and volatiles were removed under
reduced pressure. The residue was taken in tetrahydrofuran (8 mL) and cooled to 0 °C under
nitrogen. Pyrrolidine (1.21 mL; 14.64 mmol) was then added via syringe over 30 min. After the
addition was complete, the resulting mixture was allowed to warm to ambient temperature and
stirred at that temperature for 30 min. The reaction mixture was diluted with water (30 mL) and
extracted with EtOAc (25 mL × 3). Combined organic layers were washed with sat. aqueous
NaHCO3 solution, dried over anh. Na2SO4 and concentrated to obtain an yellow oil. Crude 1HꢀNMR
revealed this as a mixture of (E)ꢀ and (Z)ꢀisomers. Silica gel column chromatography (1:1
CH2Cl2/EtOAc) afforded 13 as a white crystalline solid (772 mg, 3.11 mmol; 42% yield). Melting
point: 70ꢀ72 °C; FT-IR (thin film): 2983 (w), 2886 (w), 1733 (s), 1657 (s), 1614 (s), 1447 (s),
1
1309 (s), 1266 (s), 1157 (s), 1052 (w), 985 (s), 847 (w), 763 (m), 736 (m), 668 (w); H-NMR (500
MHz, CDCl3): δ 7.33 (d, J = 15.3 Hz; 1H), 6.91 (d, J = 15.3 Hz; 1H), 4.58 (q, J = 8.5 Hz; 2H),
3.55ꢀ3.62 (m; 4H), 1.99ꢀ2.04 (m; 2H), 1.89ꢀ1.94 (m; 2H); 13C-NMR (125 MHz, CDCl3): δ 164.1,
161.8, 136.7, 128.5, 122.7 (q, J = 275 Hz), 60.6 (q, J = 36.8 Hz), 46.8, 46.2, 26.0, 24.2.
(E)ꢀN,Nꢀdimethylꢀ3ꢀnitroacrylamide (17):
N,N,N´,N´ꢀTetramethylꢀLꢀtartaramide S3 (1.00 g; 4.90 mmol) was taken in a 50 mL round bottom
flask in 20 mL dichloromethane and Pb(OAc)4 (2.61 g; 5.88 mmol) was added in one portion at rt
and the resulting suspension was stirred at rt for 30 min. The reaction mixture was filtered through a
Celite® pad and thoroughly washed with dichloromethane (50 mL). The filtrate was concentrated in
vacuo to obtain S4 as a thick colorless oil which was used immediately without further purification.
To a solution of this oil in 12 mL nitromethane at rt, neutral alumina (3.0 g) was added and
the resulting suspension was stirred at rt for 16 h. The solid was filtered through a Celite® pad and
washed with EtOAc. The filtrate was concentrated in vacuo to obtain an orange oil. Purification by

Mukherjee & Corey, Page S5
silica gel column chromatography (CH2Cl2 to 20:1 CH2Cl2/MeOH) afforded S5 as a pale yellow oil
(1.06 g, 6.54 mmol; 67% yield from S3). 1H-NMR (500 MHz, CDCl3): δ 5.04ꢀ5.07 (m; 1H), 4.56ꢀ
4.60 (m; 1H), 4.42ꢀ4.46 (m; 1H), 3.09 (s; 3H), 2.97 (s; 3H); 13C-NMR (125 MHz, CDCl3): δ 168.9,
77.8, 66.1, 36.5, 35.9.
S5 (975 mg; 6.01 mmol) was taken in a 50 mL ovenꢀdried roundꢀbottom flask together with
12 mL abs. CH2Cl2 and the resulting solution was cooled to ꢀ20 °C under nitrogen. Methanesulfonyl
chloride (1.40 mL; 18.03 mmol) was then added via syringe over 15 min followed by slow addition
of Et3N (2.51 mL; 18.03 mmol) over 10 min. The resulting yellow slurry was stirred at ꢀ20 °C for 1
h. Iceꢀcold water (50 mL) was the added to the reaction mixture and stirred vigorously at rt for 15
min. The organic layer was separated and the aqueous layer was extracted with CH2Cl2 (20 mL ×
3). Combined organic layers was washed with water (20 mL × 3) and brine (20 mL), dried over anh.
Na2SO4 and concentrated in vacuo to obtain a yellow oil. Purification by silica gel column
chromatography (1:1 hexanes/EtOAc) afforded 17 as a pale yellow crystalline solid (725 mg, 5.03
mmol; 84% yield). Melting point: 39ꢀ40 °C; FT-IR (thin film): 3112 (w), 2935 (w), 1661 (s),
1620 (s), 1526 (s), 1400 (s), 1351 (s), 1286 (w), 1257 (m), 1222 (w), 1140 (s), 1060 (m), 941 (s),
1
867 (m), 753 (s), 712 (s), 620 (s); H-NMR (500 MHz, CDCl3): δ 7.63 (d, J = 13.0 Hz; 1H), 7.58
13
(d, J = 13.0 Hz; 1H), 3.13 (s; 3H), 3.03 (s; 3H); C-NMR (125 MHz, CDCl3): δ 161.9, 147.6,
128.2, 37.9, 36.0.
(Z)ꢀEthyl 3ꢀcyanoacrylate (21):
(Z)ꢀEthyl 3ꢀcyanoacrylate 21 was prepared according to the literature procedure.2 In a 50 mL ovenꢀ
dried round bottom flask equipped with a magnetic stirring bar and a pressure equalized dropping
funnel, maleamic acid S6 (2.30 g; 20.0 mmol) was taken together with abs. dichloromethane (25
mL) under nitrogen. The resulting milky solution was cooled to 0 °C and triethylamine (5.71 mL;
41.0 mmol) was added followed by dropwise addition of ethyl chloroformate S7 (4.15 mL; 43.4
mmol) over 30 min. After the addition was complete, the reaction mixture was allowed to warm to
rt and stirred at rt for 24 h. A 10% aqueous NaOH solution was added to the reaction mixture and
the organic layer was separated. The aqueous layer was extracted with dichloromethane (20 mL ×
3) and the combined organic layers was dried over anh. MgSO4. Concentration in vacuo afforded a
pale brown oil. Purified by silica gel column chromatography (10:1 to 3:1 hexanes/Et2O) to obtain a
pale yellow oil. Further purification was achieved by bulbꢀtoꢀbulb distillation (~110 °C, 10 mmHg)
to obtain a colorless oil (1.50 g, 12.00 mmol; 60% yield). FT-IR (thin film): 3064 (w), 2987 (w),
1725 (s), 1628 (m), 1467 (w), 1385 (s), 1291 (m), 1226 (s), 1187 (s), 1096 (w), 1024 (s), 868 (w),
(2) Sauers, C. K.; Cotter, R. J. J. Org. Chem. 1961, 26, 6ꢀ10.

Mukherjee & Corey, Page S6
822 (s); 1H-NMR (500 MHz, CDCl3): δ 6.55 (d, J = 11.5 Hz; 1H), 5.94 (d, J = 11.5 Hz; 1H), 4.28
(q, J = 7.0 Hz; 2H), 1.32 (t, J = 7.0 Hz; 3H); 13C-NMR (125 MHz, CDCl3): δ 162.3, 138.3, 114.2,
110.5, 61.8, 13.8.
(E)ꢀEthyl 3ꢀcyanoacrylate (18):
(Z)ꢀEthyl 3ꢀcyanoacrylate 21 (250 mg; 2.00 mmol) was taken in a 10 mL round botton flask
together with 2 mL CH3CN and PPh3 (105 mg; 0.4 mmol) was added. The resulting solution was
refluxed at 90 °C for 48 h. The reaction mixture was then allowed to cool to ambient temperature
and concentrated in vacuo to obtain a pale brown oil. Purification by silica gel column
chromatography (10:1 to 4:1 hexanes/EtOAc, gradient) afforded 18 as a colorless oil (130 mg, 1.04
mmol; 52% yield, 65% based on recovered 21). FT-IR (thin film): 3067 (w), 2984 (w), 1722 (s),
1635 (w), 1372 (w), 1388 (s), 1293 (m), 1226 (s), 1195 (s), 1025 (s), 875 (w), 822 (s), 750 (w); 1H-
NMR (500 MHz, CDCl3): δ 6.70 (d, J = 16.8 Hz; 1H), 6.48 (d, J = 16.8 Hz; 1H), 4.28 (q, J = 7.0
Hz; 2H), 1.32 (t, J = 7.0 Hz; 3H); 13C-NMR (125 MHz, CDCl3): δ 163.2, 139.9, 115.4, 112.8, 62.1,
14.0.
(Z)ꢀ2,2,2ꢀTrifluoroethyl 3ꢀcyanoacrylate (S8):
In a 50 mL ovenꢀdried roundꢀbottom flask, maleamic acid S6 (2.00 g; 17.38 mmol) and DMAP
(425 mg; 3.48 mmol) was taken in 20 mL abs. CH2Cl2 and CF3CH2OH (3.75 mL; 3.00 mmol) was
added. The resulting milky solution was cooled to 0 °C under nitrogen and a solution of DCC (5.38
g; 26.07 mmol) in 10 mL abs. CH2Cl2 was added. After stirring for 10 min at 0 °C, the cooling bath
was removed and the reaction mixture was stirred at rt for 24 h. The reaction mixture was filtered
through a short plug of silica gel and Celite®, and washed with Et2O (50 mL). The filtrate was
concentrated in vacuo to obtain an orange oil. Purification by silica gel column chromatography
(5:1 to 2:1 hexanes/EtOAc, gradient) afforded a thick colorless oil which was further purified by
Kugelrohr distillation (85ꢀ90 °C, ~0.5 mmHg) to obtain a white crystalline solid (1.99 g, 11.1
mmol; 64% yield). Melting point: 33ꢀ34 °C; FT-IR (thin film): 3071 (w), 1749 (s), 1415 (m),
1
1389 (m), 1284 (s), 1220 (s), 1162 (s), 1043 (m), 992 (m), 962 (m), 817 (m), 652 (m); H-NMR
(500 MHz, CDCl3): δ 6.67 (d, J = 11.3 Hz; 1H), 6.10 (d, J = 11.3 Hz; 1H), 4.64 (q, J = 8.5 Hz;

Mukherjee & Corey, Page S7
2H); 13C-NMR (125 MHz, CDCl3): δ 160.7, 135.8, 122.4 (q, J = 275 Hz), 113.6, 113.1, 61.1 (q, J
= 37.0 Hz).
(E)ꢀ2,2,2ꢀTrifluoroethyl 3ꢀcyanoacrylate (S9):
To a solution of S8 (1.07 g; 5.97 mmol) in 12 mL CH2Cl2, was added PPh3 (313 mg; 1.19 mmol)
and the resulting solution was stirred at rt for 48 h. The reaction mixture was concentrated and the
residue was purified by silica gel column chromatography (10:1 to 3:1 hexanes/EtOAc, gradient) to
obtain S9 as a colorless oil (695 mg, 3.88 mmol; 65% yield, 76% yield based on recovered starting
material). FT-IR (thin film): 3086 (w), 1749 (s), 1637 (w), 1415 (m), 1320 (m), 1284 (m), 1261
(s), 1162 (s), 1050 (m), 963 (s), 843 (w), 709 (w), 646 (w); 1H-NMR (500 MHz, CDCl3): δ 6.77 (d,
13
J = 16.0 Hz; 1H), 6.59 (d, J = 16.0 Hz; 1H), 4.60 (q, J = 8.5 Hz; 2H); C-NMR (125 MHz,
CDCl3): δ 161.6, 137.4, 122.4 (q, J = 275 Hz), 115.2, 114.7, 61.2 (q, J = 37.0 Hz).
(E)ꢀEthyl 3ꢀ(4,4,5,5ꢀtetramethylꢀ1,3,2ꢀdioxaborolanꢀ2ꢀyl)acrylate (23):
CuCl (3 mol %)
Xantphos (3 mol %)
NaOtBu (6 mol %)
CO2Et
O
O
O
O
O
CO2Et
B
O
+
B
B
MeOH (2 equiv)
THF, rt
23
S10
(1.1 equiv)
20 h
S11
23 was prepared following the literature procedure.3 In an ovenꢀ and flameꢀdried 50 mL Schlenk
tube, CuCl (29.7 mg; 0.3 mmol), NaOtBu (58.0 mg; 0.6 mmol) and Xantphos (174 mg; 0.3 mmol)
was placed and dried in vacuum. The flask was backfilled with nitrogen and 9 mL abs. THF was
added. Resulting yellowish solution was stirred at rt for 60 min under nitrogen. A solution of
bis(pinacolato)diboron S11 (2.79 g; 11.0 mmol) in 7 mL abs. THF was added when the reaction
mixture became dark brown and stirred at rt for 10 min. At this point ethyl propiolate S10 (1.01 mL;
10.0 mmol) was added followed by abs. MeOH (0.81 mL; 20.0 mmol). The flask was sealed and the
resulting mixture was stirred at rt for 20 h. The reaction mixture was filtered through a Celite® pad
and washed with Et2O. Filtrate was concentrated in vacuo to obtain a brown oil. Purification by
silica gel column chromatography (10:1 to 8:1 hexanes/EtOAc) afforded 23 as a colorless oil (1.22
g, 5.4 mmol; 54% yield). FT-IR (thin film): 2980 (m), 2935 (w), 1723 (s), 1628 (m), 1468 (w),
1383 (m), 1344 (s), 1303 (s), 1260 (s), 1225 (m), 1166 (s), 1142 (s), 1112 (w), 1034 (m), 1002 (m),
(3) Lee, J.ꢀE.; Kwon, J.; Yun, J. Chem. Commun. 2008, 733ꢀ734.

Mukherjee & Corey, Page S8
1
969 (m), 902 (w), 847 (s), 725 (m), 671 (m); H-NMR (500 MHz, CDCl3): δ 6.75 (d, J = 18 Hz;
1H), 6.60 (d, J = 18 Hz; 1H), 4.19 (q, J = 7 .0 Hz; 2H), 1.25ꢀ1.28 (m; 15 H); 13C-NMR (125 MHz,
CDCl3): δ 165.9, 138.7, 83.9, 60.5, 24.7, 14.1; 11B-NMR (96 MHz, CDCl3): δ 29.7.
(E)ꢀIsopropyl 3ꢀnitroacrylate (29):
DiisopropylꢀLꢀtatrate S12 (5.00 g; 21.34 mmol) was placed in a 100 mL roundꢀbottom flask
together with 10 mL water and the resulting solution was cooled to 0 °C. NaIO4 (5.94 g; 27.75
mmol) in 40 mL water was then added dropwise with vigorous stirring over 20 min. After the
addition was complete, the resulting suspension was stirred at 0 °C for another 2 h. The reaction
mixture was allowed to warm to ambient temperature and extracted with EtOAc (30 mL × 5).
Combined extracts was dried over anh. Na2SO4 and concentrated in vacuo to obtain S13 as a
colorless oil (4.71 g) which was used immediately without further purification.
To a solution of this oil in 18 mL nitromethane at rt, neutral alumina (8.0 g) was added and
the resulting suspension was stirred at rt for 18 h. The solid was filtered through a Celite® pad and
washed with EtOAc. The filtrate was concentrated in vacuo to obtain a white solid. Purification by
silica gel column chromatography (CH2Cl2 to 50:1 CH2Cl2/MeOH) afforded S14 as a white solid
(3.30 g, 18.63 mmol; 87% yield from S12). 1H-NMR (500 MHz, CDCl3): δ 5.20 (septet, J = 6 Hz;
1H), 4.77 (d, J = 4 Hz; 2H), 4.60 (t, J = 4 Hz; 1H), 3.41 (s; 1H), 1.32 (t, J = 6 Hz; 6H); 13C-NMR
(125 MHz, CDCl3): δ 170.2, 71.4, 67.5, 21.6, 21.5.
S14 (3.04 g; 17.15 mmol) was taken in a 100 mL ovenꢀdried roundꢀbottom flask together
with 32 mL abs. CH2Cl2 and the resulting solution was cooled to ꢀ20 °C under nitrogen.
Methanesulfonyl chloride (4.0 mL; 51.45 mmol) was then added via syringe over 15 min followed
by slow addition of Et3N (7.17 mL; 51.45 mmol) over 5 min. The resulting yellow slurry was stirred
at ꢀ20 °C for 2.5 h. Iceꢀcold water (150 mL) was the added to the reaction mixture and stirred
vigorously at rt for 10 min. The organic layer was separated and the aqueous layer was extracted
with CH2Cl2 (30 mL × 3). Combined organic layers was washed with water (50 mL × 5) and brine
(50 mL), dried over anh. Na2SO4 and concentrated in vacuo to obtain a yellow oil. Purification by
silica gel column chromatography (10:1 hexanes/EtOAc) afforded 29 as a bright yellow oil (1.75 g,
11.0 mmol; 64% yield). FT-IR (thin film): 3112 (w), 2986 (m), 2940 (w), 1723 (s), 1643 (m), 1537
(s), 1469 (m), 1252 (s), 1282 (s), 1174 (s), 1146 (m), 990 (s), 948 (s), 903 (m), 820 (m), 762 (m),
673 (s); 1H-NMR (500 MHz, CDCl3): δ 7.65 (d, J = 13.5 Hz; 1H), 7.05 (d, J = 13.5 Hz; 1H), 5.15
13
(septet, J = 6.5 Hz; 1H), 1.32 (d, J = 6.5 Hz; 6H); C-NMR (125 MHz, CDCl3): δ 162.1, 148.8,
128.1, 70.4, 21.6.

Mukherjee & Corey, Page S9
• Catalytic enantioselective Diels-Alder reactions:
Methyl trifluoroethyl fumarate (4) as the dienophile:
Catalyst precursor S15 was either prepared following the previously reported procedure4 or
purchased from Sigma Aldrich Co. A 0.25M solution of oxazaborolidine S15 in toluene (0.5 mL;
0.125 mmol) was placed in a 10 mL ovenꢀ and flameꢀdried Schlenk tube and the solvent was
removed under reduced pressure. Then 0.2 mL abs. toluene was added and the resulting clear
solution was cooled to ꢀ25 °C (dry ice/isoꢀpropanol) under positive pressure of nitrogen. A solution
of Tf2NH (0.2 mL of 0.5M in abs. toluene; 0.1 mmol) was added and the resulting solution was
stirred at ꢀ25 °C for 25 min. The reaction mixture was cooled to ꢀ60 °C (dry ice/chloroform) and a
solution of methyl trifluoroethyl fumarate 4 (106 mg; 0.5 mmol) in 0.3 mL abs. toluene was added.
Cyclopentadiene (0.21 mL; 2.5 mmol) was then added down the wall of the flask over a period of
two hours and stirred at ꢀ60 °C. The reaction was monitored by TLC and judged to be complete
after 2 h. The reaction mixture was diluted with Et2O (2 mL), brought to ambient temperature and
filtered through a Celite® pad. The filtrate was concentrated in vacuo to obtain a pale yellow oil. 1Hꢀ
NMR analysis of the crude product revealed a 5:1 ratio of the two diastereomers. Purification by
silica gel column chromatography (hexanes to 10:1 hexanes/EtOAc) afforded a colorless oil (138
1
mg, 0.496 mmol; 99% yield). H-NMR (500 MHz, CDCl3): (major) δ 6.28ꢀ6.30 (m; 1H), 6.08ꢀ
6.10 (m; 1H), 4.50ꢀ4.56 (m; 1H), 4.40ꢀ4.48 (m; 1H), 3.65 (s; 3H), 3.38ꢀ3.40 (m; 1H), 3.29 (br m;
1H), 3.16 (br m; 1H), 2.78ꢀ2.79 (m; 1H), 1.57ꢀ1.59 (m; 1H), 1.48ꢀ1.50 (m; 1H); (minor) δ 6.29ꢀ6.30
(m; 1H), 6.04ꢀ6.06 (m; 1H), 4.45ꢀ4.53 (m; 1H), 4.34ꢀ4.36 (m; 1H), 3.72 (s; 3H), 3.47ꢀ3.49 (m; 1H),
3.32 (br m; 1H), 3.16 (br m; 1H), 2.69ꢀ2.71 (m; 1H), 1.62ꢀ1.64 (m; 1H), 1.48ꢀ1.50 (m; 1H).
Enantioselectivity of the two diastereomers were determined by GC analysis (CyclosilꢀB column,
110 °C isothermal: τminor = 44.7 min, τmajor = 46.8 min for major diastereomer; τmajor = 46.2 min,
τminor = 48.6 min for minor diastereomer) and found to be >99% ee for both diastereomers. See
Supporting Information: Part B for GC chromatograms.
(4) Mukherjee, S.; Corey, E. J. Org. Lett. 2010, 12, in press.

Mukherjee & Corey, Page S10
Structure determination of 5 and 6:
LiOH (1.05 equiv)
CO2H
CO2Me
CO2H
+
CO2CH2CF3
CO2Me
+
THF-H2O (2:1)
0 °C - 4 °C
16 h
CO2Me
CO2Me
CO2CH2CF3
7
S16
5
6
A solution of 5 and 6 (120 mg; 0.43 mmol) in 3:1 THFꢀH2O (2 mL) was cooled to 0 °C with an iceꢀ
bath and 2M LiOH solution (0.23 mL; 0.46 mmol) was added dropwise over 1 h. After the addition
was complete, reaction mixture was stirred at 0 °C (temperature varied between 0 and 4 °C) for 16
h. The reaction mixture was acidified with 2N HCl to pH ~2 and extracted with EtOAc (5 mL × 4).
Combined organic layers were dried over anh. Na2SO4 and concentrated in vacuo to obtain a
colorless oil. Silica gel column chromatography (CH2Cl2 to 1:1 CH2Cl2/EtOAc) afforded a white
crystalline solid (80 mg, 0.41 mmol; 95% yield). 1H-NMR (500 MHz, CDCl3): (major) δ 6.27ꢀ6.29
(m; 1H), 6.06ꢀ6.08 (m; 1H), 3.64 (s; 3H), 3.36ꢀ3.38 (m; 1H), 3.26 (br m; 1H), 3.19 (br m; 1H), 2.71ꢀ
2.72 (m; 1H), 1.59ꢀ1.61 (m; 1H), 1.46ꢀ1.48 (m; 1H); (minor) δ 6.26ꢀ6.28 (m; 1H), 6.12ꢀ6.14 (m;
1H), 3.70 (s; 3H), 3.41ꢀ3.43 (m; 1H), 3.29 (br m; 1H), 3.13 (br m; 1H), 2.64ꢀ2.66 (m; 1H), 1.59ꢀ
1.62 (m; 1H), 1.45ꢀ1.48 (m; 1H).
The solid (mixture of 7 and S16, 80 mg; 0.41 mmol) was taken in a 1:1 mixture of water and
CH2Cl2 (2 mL) and NaHCO3 (41 mg; 0.49 mmol) was added followed by a solution of I2 (125 mg;
0.49 mmol) and KI (251 mg; 1.52 mmol) in water (1 mL). The resulting mixture was stirred at rt for
2 h and quenched with sat. Na2S2O3 solution. The organic layer was separated and the aqueous layer
was acidified with 2N HCl to pH~4. Aqueous layer was extracted with EtOAc (5 mL × 4) and
combined organic layers were dried over anh. Na2SO4. Concentration in vacuo afforded a pale
yellow oil. Purification by silica gel column chromatography (CH2Cl2 to 10:1 to 3:1
CH2Cl2/EtOAc) afforded 7 as a white crystalline solid (64 mg, 0.33 mmol) and 8 as a colorless oil
(20 mg, 0.062 mmol).
(7): Melting point: 83ꢀ84 °C; FT-IR (thin film): 3250 (br), 2990 (w), 2953 (w), 1735 (s), 1700 (s),
1437 (m), 1333 (w), 1311 (w), 1268 (s), 1208 (br), 1114 (m), 1069 (w), 1024 (m),
909 (w), 865 (w), 721 (m); 1H-NMR (500 MHz, CDCl3): δ 11.5 (br; 1H), 6.27ꢀ6.29
CO2H
(m; 1H), 6.08ꢀ6.09 (m; 1H), 3.65 (s; 3H), 3.37ꢀ3.38 (m; 1H), 3.27 (br m; 1H), 3.20
CO2Me
7
13
(br m; 1H), 2.72ꢀ2.73 (m; 1H), 1.61ꢀ1.62 (m; 1H), 1.47ꢀ1.49 (m; 1H); C-NMR
(125 MHz, CDCl3): δ 180.4, 173.6, 137.5, 135.3, 51.9, 47.7, 47.6, 47.3, 47.2, 45.6; HRMS (ESI+):

Mukherjee & Corey, Page S11
Calcd for C10H12O4Na ([M+Na]+): 219.06278, Found: 219.06241; Optical rotation: [α]D23 +147.6 °
(c 0.50, CHCl3) for an enantiomerically enriched sample of >99% ee.
(8): FT-IR (thin film): 2994 (w), 2954 (w), 1795 (s), 1733 (s), 1459 (w), 1436 (m), 1349 (w), 1305
(m), 1244 (s), 1209 (s), 1176 (s), 1114 (m), 1003 (s), 958 (w), 936 (w), 919 (w);
1H-NMR (500 MHz, CDCl3): δ 5.13 (d, J = 5.0 Hz; 1H), 3.88 (d, J = 2.5 Hz;
CO2Me
I
O
1H), 3.73 (s; 3H), 3.20ꢀ3.21 (m; 1H), 3.09ꢀ3.10 (m; 1H), 3.02 (br m; 1H), 2.84 (br
O
8
13
m; 1H), 2.31ꢀ2.34 (m; 1H), 1.95ꢀ1.98 (m; 1H); C-NMR (125 MHz, CDCl3): δ
177.2, 170.6, 88.4, 52.8, 50.4, 50.1, 46.1, 40.9, 35.1, 27.8; HRMS (ESI+): Calcd for C10H11IO4Na
23
([M+Na]+): 344.95942, Found: 344.95945; Optical rotation: [α]D ꢀ35.1 ° (c 1.00, CHCl3) for an
enantiomerically enriched sample of >99% ee.
Bis(trifluoroethyl)fumarate (10) as the dienophile:
The same procedure as above was followed in CH2Cl2 at ꢀ78 °C with 0.5 mmol of 10. Purification
by silica gel column chromatography (hexanes to 5:1 hexanes/EtOAc) afforded a colorless oil (168
1
mg, 0.485 mmol; 97% yield). H-NMR (500 MHz, CDCl3): δ 6.33 (dd, J = 5.5, 3.0 Hz; 1H), 6.09
(dd, J = 5.5, 2.8 Hz; 1H), 4.32ꢀ4.62 (m; 4H), 3.49ꢀ3.50 (m; 1H), 3.36 (br m; 1H), 3.21 (br m; 1H),
2.80 (dd, J = 4.0, 1.5 Hz; 1H), 1.60ꢀ1.62 (m; 1H), 1.53ꢀ1.57 (m; 1H); 13C-NMR (125 MHz,
CDCl3): δ 172.5, 171.3, 137.8, 135.0, 122.8 (q, J = 275 Hz), 60.5 (q, J = 36.5 Hz), 47.7, 47.6, 47.3,
23
46.9, 45.8; Spectral data are in agreement with the literature.5 Optical rotation: [α]D +85.7 ° (c
1.00, CHCl3) for an enantiomerically enriched sample of >99% ee. For determination of
enantiopurity of 12, see below.
Determination of enantiomeric purity of 12:
(5) Ryu, D. H.; Zhou, G.; Corey, E. J. Org. Lett. 2005, 7, 1633ꢀ1636.

Mukherjee & Corey, Page S12
In a 10 mL ovenꢀdried roundꢀbottom flask, 12 (50 mg; 0.14 mmol) was taken in 1 mL abs. THF and
cooled to 0 °C under positive pressure of nitrogen. A 2.0M solution of LiAlH4 in THF (0.14 mL;
0.28 mmol) was then added over 10 min. After stirring for another 5 min, EtOAc was added
dropwise to the reaction mixture at 0 °C and slowly brought to rt Sat. Na2SO4 solution was added
and extracted with EtOAc (5 mL × 3). Combined organic layers were washed with brine (10 mL),
dried over anh. Na2SO4 and concentrated in vacuo to obtain a colorless oil. Silica gel column
chromatography (CH2Cl2 to 10:1 CH2Cl2/MeOH) afforded S17 as a colorless oil (20 mg, 0.13
1
mmol; 93% yield). H-NMR (500 MHz, CDCl3): δ 6.22 (dd, J = 5.3, 3.3 Hz; 1H), 5.96 (dd, J =
5.3, 2.5 Hz; 1H), 3.75 (dd, J = 9.6, 5.3 Hz; 1H), 3.63 (dd, J = 9.6, 5.0 Hz; 1H), 3.39 (t, J = 10 Hz;
1H), 3.26 (br, 2H), 3.01 (t, J = 10 Hz; 1H), 2.81 (br m; 1H), 2.58 (br m; 1H), 1.90ꢀ1.94 (m; 1H),
13
1.42ꢀ1.46 (m; 2H), 1.27ꢀ1.31 (m; 1H); C-NMR (125 MHz, CDCl3): δ 137.9, 133.4, 66.5, 65.9,
47.9, 47.1, 46.9, 44.6, 44.5; Spectral data are in agreement with the literature.6 Optical rotation:
23
[α]D ꢀ23.6 ° (c 1.00, CHCl3) for an enantiomerically enriched sample of 99% ee {Lit.7 ꢀ23.1 ° (c
1.01, CHCl3)}. The enantiopurity was determined by GC analysis (CyclosilꢀB column, 140 °C, 2
°C/min to 190 °C, τmajor = 20.8 min, τminor = 21.2 min). See Supporting Information: Part B for GC
chromatograms.
Intermolecular
competition
experiment
between
diethylfumarate
(9)
and
bisꢀ
(trifluoroethyl)fumarate (10) in asymmetric DielsꢀAlder Reaction:
A 0.25M solution of oxazaborolidine S15 in toluene (0.05 mL; 0.0125 mmol) was placed in a 10
mL ovenꢀ and flameꢀdried Schlenk tube and the solvent was removed under reduced pressure. Then
0.5 mL abs. CH2Cl2 was added and the resulting clear solution was cooled to ꢀ30 °C (dry ice/isoꢀ
propanol) under positive pressure of nitrogen. A solution of Tf2NH (0.1 mL of 0.1M in abs. CH2Cl2;
0.1 mmol) was added and the resulting solution was stirred at ꢀ30 °C for 25 min. The reaction
mixture then diluted with 2 mL abs. CH2Cl2 and stirred at ꢀ30 °C for 10 min before adding a
mixture of 9 (43 mg; 0.25 mmol) and 10 (70 mg; 0.25 mmol) in 2.2 mL abs. CH2Cl2. After stirring
the reaction mixture for another 10 min at ꢀ30 °C, cyclopentadiene (0.21 mL; 2.5 mmol) was added
down the wall of the flask over one min. Final concentration of the reaction mixture was 0.1M with
respect to 9 and 10, together. After 15 min, the reaction was quenched with Et3N (0.05 mL), diluted
(6) Maruoka, K.; Akakura, M.; Saito, S.; Ooi, T.; Yamamoto, H. J. Am. Chem. Soc. 1994, 116, 6153ꢀ6158.
(7) Achmatowicza, M.; Chapuisa, C.; Rzepeckib, P.; Jurczaka, J. Helv. Chim. Acta. 1999, 82, 182ꢀ190.

Mukherjee & Corey, Page S13
with Et2O (3 mL) and concentrated in vacuo to obtain a pale yellow oil. Conversions were
1
determined by the HꢀNMR analysis of the crude product. Enantioselectivity of 11 was determined
by GC analysis (CyclosilꢀB column, 110 °C for 10 min, then 1 °C/min to 150 °C: τminor = 46.3 min,
τ
major = 46.6 min for major diastereomer; τmajor = 46.2 min, τminor = 48.6 min for minor diastereomer)
of a sample obtained after prepꢀTLC (10:1 hexanes/EtOAc × 2) and found to be 86% ee.
Enantioselectivity of 12 was determined by converting it to the diol S17 (see above) after column
chromatographic purification of 12 (silicalgel column using CH2Cl2) and was found to be racemic.
Intermolecular competition experiment between 9 and 13 in asymmetric DielsꢀAlder Reaction:
H
Ph
Ph
20 mol %
N
O
NTf2
B
H
CO2Et
+
CO2CH2CF3
13
o-tol
1
<2% conversion
+
N
toluene (0.5M)
-60 °C, 4 h
EtO2C
9
(0.5 equiv)
(0.5 equiv)
(5 equiv)
O
A 0.25M solution of oxazaborolidine S15 in toluene (0.5 mL; 0.125 mmol) was placed in a 10 mL
ovenꢀ and flameꢀdried Schlenk tube and cooled to ꢀ25 °C (dry ice/chloroform) under positive
pressure of nitrogen. A solution of Tf2NH (0.2 mL of 0.5M in abs. toluene; 0.10 mmol) was added
and the resulting solution was stirred at ꢀ25 °C for 25 min. The reaction mixture was then cooled to
ꢀ60 °C (dry ice/chloroform) and a mixture of 9 (43 mg; 0.25 mmol) and 13 (63 mg; 0.25 mmol) in
0.3 mL abs. toluene was added. Cyclopentadiene (0.21 mL; 2.5 mmol) was added down the wall of
the flask over a period of 1 h. The reaction was monitored by TLC and no conversion was observerd
even after 4 h.
(E)ꢀ2,2,2ꢀTrifluoroethyl 4ꢀoxoꢀ4ꢀ(pyrrolidinꢀ1ꢀyl)butꢀ2ꢀenoate (13) as the dienophile:
1
The same procedure as above was followed in CH2Cl2 at 4 °C with 0.3 mmol of 13. HꢀNMR
analysis of the crude product revealed a 5:1 ratio of the two diastereomers 14 and 15, respectively.
Purification by silica gel column chromatography (hexanes to 2:1 hexanes/EtOAc) afforded 14 as a
white crystalline solid (75 mg) and 15 as a colorless oil (15 mg) (95% yield).

Mukherjee & Corey, Page S14
(14): Melting point: 66 °C; FT-IR (thin film): 2976 (m), 2877 (w), 1752 (s), 1633 (s), 1434 (s),
1334 (m), 1281 (s), 1159 (s), 1115 (s), 1083 (w), 977 (m), 914 (w), 865 (m), 723
(m); 1H-NMR (500 MHz, CDCl3): δ 6.29 (dd, J = 5.5, 3.0 Hz; 1H), 6.06 (dd, J
CO2CH2CF3
= 5.5, 2.8 Hz; 1H), 4.44ꢀ4.49 (m; 1H), 4.31ꢀ4.37 (m; 1H), 3.67ꢀ3.68 (m; 1H),
O
N
14
3.40ꢀ3.52 (m; 4H), 3.30 (br m; 1H), 2.91 (br m; 1H), 2.68ꢀ2.69 (m; 1H), 1.93ꢀ
1.98 (m; 3H), 1.81ꢀ1.88 (m; 2H), 1.40ꢀ1.42 (m; 1H); 13C-NMR (125 MHz, CDCl3): δ 172.5, 171.4,
138.1, 135.2, 122.9 (q, J = 275 Hz), 60.0 (q, J = 36.5 Hz), 47.7, 47.3, 46.6, 46.5, 46.3, 46.1, 45.6,
29.1, 24.2. Enantiopurity was determined by HPLC analysis (ChiralcelꢀOJ column, 220 nm, 90:10
hexanes/iꢀPrOH, 1.0 mL/min, τ = 5.4 and 8.9 min) and found to be racemic. See Supporting
Information: Part B for HPLC chromatograms.
(15): FT-IR (thin film): 2974 (m), 2876 (w), 1747 (s), 1635 (s), 1435 (s), 1358 (m), 1337 (s), 1280
1
(s), 1144 (s), 1076 (w), 975 (m), 861 (m), 693 (m); H-NMR (500 MHz,
O
CDCl3): δ 6.33 (dd, J = 5.8, 3.5 Hz; 1H), 6.05 (dd, J = 5.8, 3.0 Hz; 1H), 4.44ꢀ
N
CF3CH2CO2
4.54 (m; 2H), 3.53ꢀ3.58 (m; 2H), 3.44ꢀ3.49 (m; 1H), 3.35ꢀ3.40 (m; 2H), 3.21 (br
15
m; 1H), 3.18 (br m; 1H), 3.01ꢀ3.02 (m; 1H), 1.95ꢀ2.00 (m; 2H), 1.82ꢀ1.88 (m;
13
2H), 1.58ꢀ1.60 (m; 1H), 1.48ꢀ1.50 (m; 1H); C-NMR (125 MHz, CDCl3): δ 173.7, 170.4, 136.6,
134.3, 123.0 (q, J = 275 Hz), 60.3 (q, J = 36.5 Hz), 48.1, 47.8, 47.0, 46.9, 46.4, 46.2, 45.3, 26.2,
24.1. Enantiopurity was determined by HPLC analysis (ChiralcelꢀOJ column, 220 nm, 90:10
hexanes/iꢀPrOH, 1.0 mL/min, τ = 5.9 and 9.8 min) and found to be racemic. See Supporting
Information: Part B for HPLC chromatograms.
(E)ꢀN,Nꢀdimethylꢀ3ꢀnitroacrylamide (17) as the dienophile:
Same procedure as described previously was followed in CH2Cl2 at ꢀ78 °C with 0.3 mmol of 17.
1
Reaction did not proceed to completion even after 72 h and was stopped at ~90% conversion. Hꢀ
NMR analysis of the crude product revealed a >20:1 ratio of the two diastereomers S18 and S19,
respectively. Purification by silica gel column chromatography (3:1 to 1.5:1 hexanes/EtOAc
gradient) afforded S18 as a pale yellow oil (85 mg, 0.40 mmol; 80% yield). FT-IR (thin film):
2950 (m), 1638 (s), 1534 (s), 1497 (m), 1455 (w), 1399 (m), 1378 (s), 1333 (m), 1258 (m), 1147 (s),
1118 (m), 1059 (w), 958 (w), 913 (m), 870 (m), 803 (m), 774 (m), 712 (s), 680 (m); 1H-NMR (500
MHz, CDCl3): δ 6.46 (dd, J = 5.5, 3.0 Hz; 1H), 6.09 (dd, J = 5.5, 2.8 Hz; 1H), 5.63ꢀ5.65 (m; 1H),

Mukherjee & Corey, Page S15
3.55 (br m; 1H), 3.12ꢀ3.13 (m; 1H), 3.09 (s; 3H), 2.97 (s; 3H), 2.95 (br m; 1H), 1.89ꢀ1.91 (m; 1H),
13
1.52ꢀ1.54 (m; 1H); C-NMR (125 MHz, CDCl3): δ 170.7, 138.9, 134.2, 88.2, 47.7, 46.9, 46.6,
45.3, 37.2, 35.9. Enantiopurity was determined by HPLC analysis (ChiralpakꢀAD column, 220 nm,
90:10 hexanes/iꢀPrOH, 1.0 mL/min, τ = 8.8 and 11.2 min) and found to be racemic. See Supporting
Information: Part B for HPLC chromatograms.
(E)ꢀEthyl 3ꢀcyanoacrylate (18) as the dienophile:
A 0.25M solution of oxazaborolidine Sx in toluene (0.5 mL; 0.125 mmol) was placed in a 10 mL
ovenꢀ and flameꢀdried Schlenk tube and the solvent was removed under reduced pressure. Then 0.3
mL abs. CH2Cl2 was added and the resulting clear solution was cooled to ꢀ25 °C (dry ice/isoꢀ
propanol) under positive pressure of nitrogen. A solution of Tf2NH (0.2 mL of 0.5M in abs. CH2Cl2;
0.1 mmol) was added and the resulting solution was stirred at ꢀ25 °C for 25 min. The reaction
mixture was then cooled to ꢀ78 °C and a solution of 18 (63 mg; 0.5 mmol) in 0.5 mL abs. CH2Cl2
was added. Cyclopentadiene (0.21 mL; 2.5 mmol) was then added down the wall of the flask over a
period of 2 h and stirred at ꢀ78 °C for another 6 h. The reaction mixture was diluted with Et2O (2
mL), brought to ambient temperature and filtered through a Celite® pad. The filtrate was
1
concentrated in vacuo to obtain a colorless oil. HꢀNMR analysis of the crude product revealed a
10:1 ratio of the two diastereomers 19 and 20, respectively. Purification by silica gel column
chromatography (10:1 hexanes/EtOAc) afforded a colorless oil (91 mg, 0.475 mmol; 95% yield).
Enantioselectivity of 19 and 20 were determined by GC analysis (CyclosilꢀB column, 135 °C
isothermal: τmajor = 30.6 min, τminor = 36.1 min for 19; τminor = 29.5 min, τmajor = 31.1 min for 20) and
found to be 97% ee for 19 and 75% ee for 20. See Supporting Information: Part B for GC
1
chromatograms. H-NMR (500 MHz, CDCl3): δ (19) 6.21 (dd, J = 5.8, 3.3 Hz; 1H), 6.05 (dd, J =
5.8, 3.0 Hz; 1H), 4.10ꢀ4.15 (m; 2H), 3.38 (br m; 1H), 3.27 (br m; 1H), 3.25 (t, J = 4.0 Hz; 1H), 2.70
(dd, J =4.0, 2.0 Hz; 1H), 1.72ꢀ1.74 (m; 1H), 1.65ꢀ1.67 (m; 1H), 1.25 (t, J = 7.3 Hz; 3H); 13C-NMR
(125 MHz, CDCl3): δ (19) 171.1, 136.0, 134.8, 122.1, 61.2, 50.1, 48.3, 48.2, 45.9, 31.1, 14.1.

Mukherjee & Corey, Page S16
(Z)ꢀEthyl 3ꢀcyanoacrylate (21) as the dienophile:
Same procedure as for the reaction using 18 as the dienophile was followed on a 0.50 mmol scale.
1HꢀNMR analysis of the crude product revealed a 8:1 endo/exo ratio in favor of the endoꢀproduct
22. After purification using silica gel column chromatography (10:1 to 5:1 hexanes/EtOAc), product
(22) was obtained as a colorless oil (80 mg, 0.42 mmol; combined yield = 94%). FT-IR (thin film):
2985 (m), 2878 (w), 2240 (m), 1735 (s), 1455 (w), 1373 (m), 1334 (m), 1251 (m), 1226 (w), 1188
1
(s), 1144 (w), 1096 (w), 1042 (s), 912 (w), 835 (w), 767 (w), 738 (m), 639 (w); H-NMR (500
MHz, CDCl3): δ 6.46 (dd, J = 5.8, 2.8 Hz; 1H), 6.31 (dd, J = 5.8, 2.5 Hz; 1H), 4.13ꢀ4.19 (m; 2H),
3.23ꢀ3.30 (m; 4H), 1.56ꢀ1.57 (m; 1H), 1.30ꢀ1.32 (m; 1H), 1.27 (t, J = 7.3 Hz; 3H); 13C-NMR (125
MHz, CDCl3): δ 170.4, 137.9, 133.9, 119.9, 61.1, 48.6, 47.9, 46.8, 44.9, 33.1, 14.1; HRMS
(ESI+): Calcd for C11H14NO2 ([M+H]+): 192.10191, Found: 192.10199; Calcd for C11H13NO2Na
23
([M+Na]+): 214.08385, Found: 214.08411; Optical rotation: [α]D ꢀ50.5 ° (c 1.00, CHCl3) for an
enantiomerically enriched sample of 92% ee. Enantipurity was determined by GC analysis
(CyclosilꢀB column, 150 °C isothermal: τminor = 25.5 min, τmajor = 27.1 min). See Supporting
Information: Part B for GC chromatograms.
(Z)ꢀ2,2,2ꢀTrifluoroethyl 3ꢀcyanoacrylate (S8) as the dienophile:
H
Ph
Ph
20 mol %
N
O
NTf2
B
H
o-tol
1
NC
+
CH2Cl2
CO2CH2CF3
CN
S20
CO2CH2CF3
-78 °C, 20 h
S8
1
Same procedure as above was followed on a 0.50 mmol scale. HꢀNMR analysis of the crude
product revealed a 6:1 endo/exo ratio in favor of the endoꢀproduct S20. After purification using
silica gel column chromatography (10:1 to 5:1 hexanes/EtOAc), S20 was obtained as a colorless oil
(102 mg, 0.42 mmol; combined yield = 92%). FT-IR (thin film): 2986 (w), 1758 (s), 1453 (w),
1412 (m), 1337 (m), 1280 (s), 1157 (s), 1064 (m), 988 (m), 912 (w), 835 (m), 769 (w), 739 (m), 666
(w); 1H-NMR (500 MHz, CDCl3): δ 6.41 (dd, J = 6.0, 3.0 Hz; 1H), 6.34 (dd, J = 6.0, 2.8 Hz; 1H),
4.58ꢀ4.66 (m; 1H), 4.29ꢀ4.36 (m; 1H), 3.31ꢀ3.39 (m; 4H), 1.58ꢀ1.61 (m; 1H), 1.34ꢀ1.36 (m; 1H);
13C-NMR (125 MHz, CDCl3): δ 168.9, 137.2, 134.6, 122.7 (q, J = 275 Hz), 119.4, 60.5 (q, J =

Mukherjee & Corey, Page S17
36.5 Hz), 48.0, 47.9, 46.8, 45.1, 33.0; Enantipurity was determined by GC analysis (CyclosilꢀB
column, 140 °C, 1 °C/min to 160 °C, 160 °C for 2 min: τminor = 18.9 min, τmajor = 21.2 min) and
found to be 62% ee. See Supporting Information: Part B for GC chromatograms.
(E)ꢀ2,2,2ꢀTrifluoroethyl 3ꢀcyanoacrylate (S9) as the dienophile:
1
Same procedure was above was followed on a 0.5 mmol scale. HꢀNMR analysis of the crude
product revealed a 3.5:1 ratio of the two diastereomers S21 and S22, respectively. Purification by
silica gel column chromatography (hexanes to 8:1 hexanes/EtOAc) afforded a colorless oil (114 mg,
0.46 mmol; 92% yield). Enantioselectivity of S21 and S22 were determined by GC analysis
(CyclosilꢀB column, 120 °C, 1 °C/min to 150 °C, 150 °C for 1 min: τmajor = 23.5 min, τminor = 28.7
min for S21; τminor = 23.2 min, τmajor = 23.9 min for S22) and found to be 42% ee for S21 and 15%
ee for S22. See Supporting Information: Part B for GC chromatograms.
(S21): 1H-NMR (500 MHz, CDCl3): δ 6.23 (dd, J = 5.5, 3.0 Hz; 1H), 6.03 (d, J = 5.5, 2.8 Hz; 1H),
4.53ꢀ4.62 (m; 1H), 4.32ꢀ4.40 (m; 1H), 3.43 (br m; 1H), 3.34ꢀ3.35 (m; 1H), 3.30 (br m; 1H), 2.69ꢀ
13
2.70 (m; 1H), 1.74ꢀ1.76 (m; 1H), 1.68ꢀ1.1.71 (m; 1H); C-NMR (125 MHz, CDCl3): δ 169.7,
136.5, 134.4, 122.6 (q, J = 275 Hz), 121.5, 60.5 (q, J = 36.5 Hz), 49.6, 48.3, 48.2, 46.1, 31.2.
(S22): 1H-NMR (500 MHz, CDCl3): δ 6.43 (dd, J = 5.3, 3.3 Hz; 1H), 6.35 (dd, J = 5.3, 2.5 Hz;
1H), 4.56ꢀ4.60 (m; 1H), 4.40ꢀ4.46 (m; 1H), 3.43 (br m; 1H), 3.31ꢀ3.33 (m; 1H), 3.24 (br m; 1H),
13
2.63ꢀ2.64 (m; 1H), 1.55ꢀ1.57 (m; 1H), 1.49ꢀ1.51 (m; 1H); C-NMR (125 MHz, CDCl3): 171.0,
138.3, 135.7, 121.5 (q, J = 275 Hz), 121.0, 60.5 (q, J = 36.5 Hz), 49.8, 47.8, 46.0, 45.9, 32.1.
(E)ꢀEthyl 3ꢀ(4,4,5,5ꢀtetramethylꢀ1,3,2ꢀdioxaborolanꢀ2ꢀyl)acrylate (23) as the dienophile:

Mukherjee & Corey, Page S18
A 0.25M solution of oxazaborolidine Sx in toluene (0.5 mL; 0.125 mmol) was placed in a 10 mL
ovenꢀ and flameꢀdried Schlenk tube and the solvent was removed under reduced pressure. Then 0.2
mL abs. CH2Cl2 was added and the resulting clear solution was cooled to ꢀ25 °C (dry ice/isoꢀ
propanol) under positive pressure of nitrogen. A solution of Tf2NH (0.2 mL of 0.5M in abs. CH2Cl2;
0.1 mmol) was added and the resulting solution was stirred at ꢀ25 °C for 25 min. Solvent was then
removed under reduced pressure at ꢀ25 °C. A solution of 23 (113 mg; 0.5 mmol) in 0.4 mL abs.
CH2Cl2 was added to the residue and the solvent was removed again at ꢀ25 °C. The residue was
taken in 0.3 mL abs. CH2Cl2 and the reaction mixture was cooled to ꢀ78 °C (dry ice/isoꢀpropanol).
Cyclopentadiene (0.21 mL; 2.5 mmol) was then added down the wall of the flask over a period of 2
h and stirred at ꢀ78 °C for another 5 h. The reaction mixture was diluted with Et2O (2 mL), brought
to ambient temperature and filtered through a Celite® pad. The filtrate was concentrated in vacuo to
obtain a pale yellow oil. Purification by silica gel column chromatography (hexanes to 5:1
hexanes/EtOAc) afforded 24 as a white solid (134 mg, 0.46 mmol; 92% yield). Melting point: 34ꢀ
35 °C; FT-IR (thin film): 3060 (w), 2978 (m), 2935 (w), 1732 (s), 1468 (w), 1408 (w), 1370 (s),
1317 (s), 1269 (m), 1253 (m), 1192 (m), 1167 (m), 1143 (s), 1107 (s), 1059 (w), 1032 (m), 973 (s),
1
909 (m), 852 (s), 729 (s), 690 (m); H-NMR (500 MHz, CDCl3): δ 6.25 (dd, J = 5.8, 3.3 Hz; 1H),
5.85 (dd, J = 5.8, 2.5 Hz; 1H), 4.00ꢀ4.09 (m; 2H), 3.21 (br m; 1H), (3.06, J = 4.8, 3.8 Hz; 1H), 2.92
13
(br m; 1H), 1.16ꢀ1.32 (m; 17 H); C-NMR (125 MHz, CDCl3): δ 174.8, 139.2, 131.4, 83.3, 60.0,
48.6, 46.4, 46.0, 45.3, 24.7, 24.6, 14.2; 11B-NMR (96 MHz, CDCl3): δ 34.0; HRMS (ESI+): Calcd
for C16H26BO4 ([M+H]+): 293.19187, Found: 293.19135; Calcd for C16H25BO4 ([M+Na]+):
23
315.17381, Found: 315.17324; Optical rotation: [α]D +100.0 ° (c 2.00, CHCl3) for an
enantiomerically enriched sample of >99% ee. See below for the determination of enantiomeric
purity.
Determination of enantiomeric purity of 24:
50% H2O2
O
KHCO3
OH
B
O
THF-EtOH
0 °C, 4.5 h
CO2Et
CO2Et
25
24
In a 25 mL roundꢀbottom flask, 24 (80 mg; 0.27 mmol) was placed together with 3:1 THFꢀEtOH
(2.5 mL) and the resulting solution was cooled to 0 °C. A 2.0M aqeous KHCO3 solution (0.27 mL;
0.54 mmol) was added followed by slow addition of H2O2 (0.062 mL; 1.08 mmol) over 10 min. The
resulting mixture was stirred at 0 °C for 4.5 h. The reaction was quenched with sat. Na2S2O3 and
extracted with EtOAc (5 mL × 3). Combined organic layers was washed with water (10 mL) and
brine (10 mL), dried over anh. Na2SO4 and concentrated to obtain a colorless oil. Purified by silica
gel column chromatography (5:1 to 2:1 hexanes/EtOAc) afforded 25 as a colorless oil (47 mg, 0.26
mmol; 96% yield). FT-IR (thin film): 3432 (br), 3066 (w), 2979 (m), 2941 (w), 2874 (w), 1731

Mukherjee & Corey, Page S19
(w), 1713 (s), 1448 (m), 1370 (m), 1327 (m), 1255 (m), 1187 (s), 1114 (s), 1096 (m), 1030 (s), 997
(w), 979 (m), 917 (w), 858 (m), 822 (w), 777 (w), 716 (s), 695 (s); 1H-NMR (500 MHz, CDCl3): δ
6.14 (dd, J = 5.8, 2.8 Hz; 1H), 6.07 (dd, J = 5.8, 3.3 Hz; 1H), 4.06ꢀ4.13 (m; 3H), 3.09 (br m; 1H),
2.82 (br s; 1H), 2.77 (br m; 1H), 2.63 (t, J = 3.0 Hz; 1H), 1.82ꢀ1.90 (m; 1H), 1.63ꢀ1.65 (m; 1H),
13
1.23 (t, J = 7.0 Hz; 3H); C-NMR (125 MHz, CDCl3): δ 173.6, 137.1, 134.6, 75.5, 60.4, 55.0,
50.4, 46.3, 44.0, 14.2; HRMS (ESI+): Calcd for C10H14O3Na ([M+Na]+): 205.08352, Found:
23
205.08362; Optical rotation: [α]D +137.0 ° (c 2.00, CHCl3) for an enantiomerically enriched
sample of >99% ee. The enantiomeric purity was determined by GC analysis (CyclosilꢀB column,
150 °C for 5 min, 1 °C/min to 160 °C, 160 °C for 5 min: τminor = 14.1 min, τmajor = 15.1 min). See
Supporting Information: Part B for GC chromatograms.
Dehydration of 25 to the diene 26:
Alcohol 25 (25 mg; 0.14 mmol) was placed in a 10 mL flameꢀdried roundꢀbottom flask together
with 0.5 mL abs. CH2Cl2 and cooled to ꢀ20 °C under nitrogen. Methanesulfonyl chloride (0.013 mL;
0.168 mmol) was then added followed by Et3N (0.023 mL; 0.168 mmol). The resulting mixture was
stirred at ꢀ20 °C for 15 min. Water and CH2Cl2 was added to the reaction mixture and allowed to
warm to ambient temperature. Organic layer was separated and the aqueous layer was extracted
with CH2Cl2 (5 mL × 2). The combined organic layer was dried over anh. Na2SO4 and concentrated
in vacuo to obtain S23 as a pale yellow oil (36 mg) which was pure enough to be used as such for
the next step. 1H-NMR (500 MHz, CDCl3): δ 6.22 (dd, J = 5.9, 2.8 Hz; 1H), 6.09 (dd, J = 5.8, 3.5
Hz; 1H), 4.81 (m; 1H), 4.05ꢀ4.17 (m; 2H), 3.19 (br m; 1H), 3.15 (br m; 1H), 3.07 (s; 3H), 2.94ꢀ2.96
(m; 1H), 1.86ꢀ1.88 (m; 1H), 1.74ꢀ1.76 (m; 1H), 1.24 (t, J = 7.0 Hz; 3H).
S23 (36 mg; 0.14 mmol) was taken in 0.5 mL abs. THF in a 10 mL roundꢀbottom flask and
cooled to ꢀ78 °C under nitrogen. A 1.0M solution of LHMDS in THF (0.35 mL; 0.35 mmol) was
added via syringe over 20 min. Sat. NH4Cl solution was added to the reaction mixture and allowed
to warm to ambient temperature. The resulting mixture was extracted with Et2O (5 mL × 3). The
combined extracts was dried over anh. Na2SO4 and concentrated in vacuo to obtain a pale yellow
oil. Purification by silica gel column chromatography (5:1 hexanes/EtOAc) afforded 26 as a
colorless oil (20 mg, 0.12 mmol; 87% yield from 25). FT-IR (thin film): 3031 (w), 2976 (w), 2920
(m), 2850 (w), 1707 (s), 1595 (m), 1556 (m), 1463 (w), 1367 (m), 1318 (s), 1289 (s), 1238 (s), 1151
1
(s), 1097 (s), 1061 (s), 1023 (m), 876 (w), 759 (s), 724 (w), 695 (s); H-NMR (500 MHz, CDCl3):
δ 7.64 (d, J = 3.0 Hz; 1H), 6.93 (dd, J = 5.0, 3.0 Hz; 1H), 6.74 (dd, J = 5.0, 3.3 Hz; 1H), 4.20 (q, J =
13
7.0 Hz; 2H), 3.91 (br m; 1H), 3.72 (br m; 1H), 2.12ꢀ2.17 (m; 2H), 1.30 (t, J = 7.0; 3H); C-NMR

Mukherjee & Corey, Page S20
(125 MHz, CDCl3): δ 165.0, 155.5, 149.8, 143.7, 141.8, 74.4, 60.2, 51.5, 50.0, 14.3; HRMS
23
(ESI+): Calcd for C10H13O2 ([M+H]+): 165.09101, Found: 165.09144; Optical rotation: [α]D
ꢀ
40.0 ° (c 0.30, CHCl3) for an enantiomerically enriched sample of >99% ee. The enantiomeric
purity was determined by GC analysis (CyclosilꢀB column, 120 °C isotherm: τminor = 13.2 min, τmajor
= 14.3 min). See Supporting Information: Part B for GC chromatograms.
(27): Same procedure as above was followed in 0.5 mmol scale and the reaction was complete
within 2 h. Purification by silica gel column chromatography (hexanes to 10:1
O
hexanes/EtOAc) afforded pure 27 as a colorless oil (150 mg, 0.49 mmol; 98%
B
O
yield). FT-IR (thin film): 2977 (m), 2933 (w), 1869 (w), 1733 (s), 1626 (w),
Me
CO2Et
27
1445 (m), 1407 (w), 1370 (s), 1315 (s), 1262 (s), 1213 (m), 1166 (s), 1143 (s),
1105 (s), 1060 (w), 1035 (m), 970 (m), 912 (w), 894 (w), 855 (s), 786 (m), 667 (w); 1H-NMR (500
MHz, CDCl3): δ 5.36 (br m; 1H), 3.99ꢀ4.05 (m; 2H), 3.06ꢀ3.08 (m; 2H), 2.65 (br m; 1H), 1.74 (m;
13
3H), 1.33ꢀ1.36 (m; 1H), 1.27ꢀ1.29 (m; 1H), 1.19ꢀ1.25 (m; 15 H); C-NMR (125 MHz, CDCl3): δ
11
175.0, 149.5, 124.5, 83.3, 59.9, 50.0, 48.3, 48.2, 47.1, 24.7, 24.6, 14.9, 14.2; B-NMR (96 MHz,
CDCl3): δ 34.1; HRMS (ESI+): Calcd for C17H28BO4 ([M+H]+): 307.20752, Found: 307.20761;
Calcd for C17H27BO4Na ([M+Na]+): 329.18946, Found: 329.18973; Optical rotation: [α]D23 +112.0
° (c 1.00, CHCl3) for an enantiomerically enriched sample of 99% ee. The enantiomeric purity was
determined by converting to the corresponding alcohol (28) and GCꢀanalysis (see below).
(28): Same procedure as above was followed in 0.18 mmol scale. Purification by silica gel column
chromatography (5:1 to 2:1 hexanes/EtOAc) afforded pure 28 as a colorless oil (34
mg, 0.17 mmol; 94% yield). FT-IR (thin film): 3436 (br), 2969 (m), 2938 (w),
OH
Me
CO2Et 2874 (w), 1731 (s), 1714 (s), 1630 (w), 1444 (m), 1370 (m), 1315 (w), 1255 (s),
28
1185 (s), 1112 (s), 1049 (s), 1023 (s), 982 (m), 930 (m), 907 (w), 857 (w), 824 (m),
1
785 (w); H-NMR (500 MHz, CDCl3): δ 5.60 (br m; 1H), 4.04ꢀ4.09 (m; 3H), 2.96ꢀ2.98 (m; 1H),
2.63ꢀ2.64 (m; 1H), 2.51 (br m; 1H), 2.40 (br s; 1H), 1.81ꢀ1.83 (m; 1H), 1.70ꢀ1.72 (m; 3H), 1.63ꢀ
13
1.66 (m; 1H), 1.19ꢀ1.23 (m; 3H); C-NMR (125 MHz, CDCl3): δ 173.7, 145.0, 129.1, 75.3, 60.3,
57.2, 55.2, 46.0, 44.9, 15.3, 14.2; HRMS (ESI+): Calcd for C11H16O3Na ([M+Na]+): 219.09917,
23
Found: 219.09900; Optical rotation: [α]D +146.0 ° (c 1.00, CHCl3) for an enantiomerically
enriched sample of 99% ee. The enantiomeric purity was determined GC analysis (CyclosilꢀB
column, 150 °C for 5 min, 1 °C/min to 170 °C, 170 °C for 5 min, τminor = 13.9 min, τmajor = 14.7
min). See Supporting Information: Part B for GC chromatograms.

Mukherjee & Corey, Page S21
(E)ꢀIsopropyl 3ꢀnitroacrylate (29) as the dienophile:
A 0.25M solution of oxazaborolidine Sx in toluene (1.5 mL; 0.375 mmol) was placed in a 10 mL
ovenꢀ and flameꢀdried Schlenk tube and the solvent was removed under reduced pressure. Then 1.0
mL abs. CH2Cl2 was added and the resulting clear solution was cooled to ꢀ25 °C (dry ice/isoꢀ
propanol) under positive pressure of nitrogen. A solution of Tf2NH (0.6 mL of 0.5M in abs. CH2Cl2;
0.30 mmol) was added followed by 0.3 mL abs. CH2Cl2 and the resulting solution was stirred at ꢀ25
°C for 25 min. The resulting mixture was then cooled to ꢀ95 °C (hexanes/liq. N2) and
cyclopentadiene (0.62 mL; 7.50 mmol) was slowly added along the wall of the flask over a few
mins. After 10 min, a solution of 29 (239 mg; 1.50 mmol) in 1.0 ml abs. CH2Cl2 was added slowly
over 2.5 h. The reaction was found to be complete immediately after the addition was complete
(monitored by TLC). Methanol (0.5 mL) was added to the reaction mixture followed by Et2O (3
mL) and allowed to warm to ambient temperature, filtered through a Celite® pad and the filatrate
was concentrated in vacuo to obtain an orange oil. 1HꢀNMR analysis of the crude product revealed a
1.5:1 ratio of the two diastereomers 30 and 31, respectively. Purification by silica gel column
chromatography (hexanes to 10:1 hexanes/EtOAc) afforded a colorless oil (318 mg, 1.41 mmol;
94% yield). Enantioselectivity of 30 and 31 were determined by GC analysis (CyclosilꢀB column,
130 °C isothermal: τminor = 46.0 min, τmajor = 50.1 min for 30; τmajor = 49.3 min, τminor = 55.1 min for
31) and found to be 91% ee for 30 and >99% ee for 31. See Supporting Information: Part B for GC
chromatograms.
(30): 1H-NMR (500 MHz, CDCl3): δ 6.46 (dd, J = 5.5, 3.3 Hz; 1H), 6.06 (dd, J = 5.5, 3.0 Hz; 1H),
5.40 (t, J = 3.8 Hz; 1H), 5.04 (septet, J = 6.0 Hz; 1H), 3.59 (br m; 1H), 3.19 (br m; 1H), 2.98 (t, J =
3.0 Hz; 1H), 1.68ꢀ1.70 (m; 1H), 1.58ꢀ1.61 (m; 1H), 1.24ꢀ1.27 (6H).
1
(31): H-NMR (500 MHz, CDCl3): δ 6.21ꢀ6.22 (m; 2H), 4.97 (septet, J = 6.0 Hz; 1H), 4.69ꢀ4.70
(m; 1H), 3.64 (t, J = 3.8 Hz; 1H), 3.47 (br m; 1H), 3.32 (br m; 1H), 1.86ꢀ1.88 (m; 1H), 1.68 (m;
1H), 1.20ꢀ1.23 (m; 6H).

Mukherjee & Corey, Page S22
Conversion of 30 and 31 to their corresponding β–amino acid derivatives:
The mixture of 30 and 31 (250 mg; 1.11 mmol) was placed in a 200 mL roundꢀbottom flask
together with 50 mL THFꢀH2O mixture (20:1) and the resulting solution was cooled to 0 °C.
Aluminum foil, cut into small pieces (600 mg; 22.2 mmol; washed with Et2O, dipped into 2%
aqueous HgCl2 solution and washed again with MeOH and Et2O), was then added to the solution at
0 °C with vigorous stirring. The resulting mixture was stirred vigorously at 0 – 4 °C for 24 h. The
reaction mixture (dark grey suspension) was filtered through a Celite® pad and washed with 1:1
THFꢀMeOH (100 mL). The filtrate was concentrated in vacuo and the residue was taken in CH2Cl2,
dried over anh. Na2SO4 and concentrated to obtain a pale yellow oil. Purification by silica gel
column chromatography (20:1 to 5:1 CH2Cl2ꢀMeOH) afforded a colorless oil (206 mg, 1.06 mmol;
1
95% yield). H-NMR (500 MHz, CDCl3): δ (major) 6.39 (dd, J = 5.8, 3.3 Hz; 1H), 6.19 (dd, J =
5.8, 3.0 Hz; 1H), 5.01 (septet, J = 6.3 Hz; 1H), 3.67 (t, J = 2.8 Hz; 1H), 2.95 (br m; 1H), 2.83 (br m;
1H), 2.38 (t, J = 3.5 Hz; 1H), 1.68ꢀ1.70 (m; 1H), 1.55ꢀ1.58 (m; 1H), 1.45ꢀ1.47 (br m; 2H), 1.22ꢀ1.24
(m; 6H); δ (minor) 6.15 (dd, J = 5.8, 3.3 Hz; 1H), 6.06 (dd, J = 5.8, 2.8 Hz; 1H), 4.94 (septet, J =
6.0 Hz; 1H), 3.15ꢀ3.16 (m; 1H), 3.07 (br m; 1H), 2.55 (br m; 1H), 1.75ꢀ1.77 (m; 1H), 1.69ꢀ1.70 (m;
1H), 1.45ꢀ1.47 (br m; 2H), 1.18ꢀ1.20 (m; 6H).
To a solution of this oil (140 mg; 0.72 mmol) and K2CO3 (109 mg; 0.79 mmol) in 1:1
MeOHꢀH2O (25 mL), was added Boc2O (173 mg; 0.79 mmol) and the resulting solution was stirred
at rt for 3 h. MeOH was then removed in vacuo, the residue was acidified with 5% citric acid
solution to pH ~3 and extracted with CH2Cl2 (10 mL × 3). Combined extracts was dried over anh.
Na2SO4 and concentrated in vacuo to obtain a pale yellow oil. Purification by silica gel column
chromatography (10:1 to 5:1 hexanes/EtOAc gradient) afforded 32 (126 mg) and 33 (85 mg) as
white crystalline solids (0.71 mmol; >99% yield).
(32): Melting point: 61ꢀ62 °C; FT-IR (thin film): 3371 (br), 2978 (m), 2918 (w), 1703 (s), 1504
(m), 1455 (w), 1366 (s), 1249 (s), 1164 (s), 1106 (s), 1045 (w), 1024 (w), 942 (w),
1
i
CO2 Pr
861 (w), 729 (m); H-NMR (500 MHz, CDCl3): δ 6.38 (dd, J = 5.5, 3.0 Hz; 1H),
NHBoc
6.14 (dd, J = 5.5, 2.8 Hz; 1H), 5.01 (septet, J = 6.0 Hz; 1H), 4.44 (br s; 1H), 4.25ꢀ
32
4.28 (br m; 1H), 2.99 (br s; 1H), 2.93 (s; 1H), 1.77ꢀ1.79 (m; 2H), 1.43ꢀ1.45 (m; 1H), 1.40 (s; 9H),
13
1.21ꢀ1.23 (m; 6H); C-NMR (125 MHz, CDCl3): δ 173.6, 155.1, 139.4, 134.1, 79.1, 67.8, 55.3,
53.1, 47.1, 46.2, 46.0, 29.6, 28.2, 21.7; HRMS (ESI+): Calcd for C16H25NO4Na ([M+Na]+):

Mukherjee & Corey, Page S23
23
318.16758, Found: 318.16783; Optical rotation: [α]D +97.6 ° (c 1.00, CHCl3) for an
enantiomerically enriched sample of 91% ee.
(33): Melting point: 79ꢀ80 °C; FT-IR (thin film): 3370 (br), 2978 (m), 2933 (w), 1713 (s), 1517
(s), 1456 (w), 1366 (m), 1284 (m), 1253 (m), 1170 (s), 1106 (s), 1046 (m), 1027
1
NHBoc
(w), 979 (w), 907 (w), 882 (w), 748 (w), 716 (m); H-NMR (500 MHz, CDCl3): δ
CO2iPr
6.18 (dd, J = 5.5, 3.5 Hz; 1H), 6.04 (br m; 1H), 4.94 (septet, J = 6.0 Hz; 1H), 4.80
33
(br s; 1H), 3.78 (br s; 1H), 3.09 (s; 1H), 2.82 (br s; 1H), 2.48 (br s; 1H), 1.55ꢀ1.60 (m; 2H), 1.43 (s;
13
9H), 1.17ꢀ1.24 (m; 6H); C-NMR (125 MHz, CDCl3): δ 172.2, 155.1, 136.0, 135.1, 79.2, 67.6,
54.8, 52.9, 48.9, 46.7, 44.8, 29.6, 28.3, 21.7; HRMS (ESI+): Calcd for C16H25NO4Na ([M+Na]+):
23
318.16758, Found: 318.16736; Optical rotation: [α]D +76.7 ° (c 1.00, CHCl3) for an
enantiomerically enriched sample of >99% ee.