A reductive-coupling plus nazarov cyclization sequence in the asymmetric synthesis of five-membered carbocycles

Article abstract of DOI:10.1021/jo100736p

Palladium-mediated hydrostannylation of alkynoyl compounds is combined with Stille-Scott cross-coupling (reductive-coupling) to give one-pot access to divinyl and aryl vinyl ketones, which undergo Nazarov cyclization to give cyclopentenones upon treatment with acid. This reaction sequence has been studied with a variety of different substitution patterns, including the use of oxazolidinone auxiliaries to achieve torquoselectivity in the Nazarov cyclization. Through a combination of good yields and moderate to good levels of stereochemical induction, this approach affords efficient, convergent, and asymmetric access to a variety of different cyclopentanoid systems.

Full text of DOI:10.1021/jo100736p

Supplementary Information
A Reductive-Coupling plus Nazarov Cyclization Sequence in the
Asymmetric Synthesis of Five-Membered Carbocycles
Daniel J. Kerr, Jonathan M. White, Bernard L. Flynn
Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, 381 Royal Parade,
Parkville Vic 3052, Australia.
CONTENTS
I.
NMR Tables for Selected Products 31.............................................................................................................................2
Extended Listing of Reaction Conditions used in the Cyclisation 30 to 31.....................................................................4
Crystallographic data for 31aC and 31hA........................................................................................................................5
Experimental Details........................................................................................................................................................6
II.
III.
IV.
V.
1
13
H and C (JMOD or APT) NMR Spectra....................................................................................................................25
VI.
VII.
Enantiopurity Determination of Hydrolysis Product R-21 by Chiral HPLC ...............................................................111
Determination of 30g Stereochemistry by NOESY NMR Spectroscopy ....................................................................112
VIII. Asymmetric Nazarov Reaction Crude NMR Spectra (Determination of Product Distribution for Tables 4 and 8)....113
S-1

I. NMR Tables for Selected Products 31
Table 5: H NMR comparison of trans-Nazarov products bearing the (S)-4-phenyloxazolidin-2-one auxiliary.
1
4
5
a
b
c
4,5
a,b
a,c
b,c
H
H
H
H
H
J
J
J
J
Entry
Product
R
f
(
ppm)
(ppm)
(ppm)
(ppm)
(ppm)
(Hz) (Hz) (Hz) (Hz)
3
3
1aA: Minor, S-β-trans
1aC: Major, S-α-trans
High
Low
4.92
4.89
3.22
3.12
5.46
5.43
4.71
4.76
4.21
4.31
br s
3.0
9.0
8.3
5.9
2.5
8.9
8.7
1
2
3
4
5
6
7
3
3
1eA: Minor, S-β-trans
1eC: Major, S-α-trans
High
Low
4.93
4.86
3.25
3.05
5.49
5.43
4.74
4.75
4.25
4.29
br s
1.8
9.0
8.4
6.2
2.7
8.9
8.7
3
3
1fA: Minor, S-β-trans
1fC: Major, S-α-trans
High
Low
5.18
5.14
3.85
3.74
5.52
5.49
4.77
4.81
4.29
4.35
br s
4.2
9.0
8.4
5.7
2.8
9.0
8.9
3
3
1gA: Major, S-β-trans
1gC: Minor S-α-trans
High
Low
5.20
5.18
4.41
4.30
5.43
5.41
4.66
4.75
4.21
4.27
2.1
3.0
9.0
8.4
5.7
2.7
8.7
8.7
3
3
1hA: Major, S-β-trans
1hC: Minor, S-α-trans
High
Low
5.16
5.13
4.43
4.24
5.43
5.42
4.66
4.74
4.21
4.26
br s
2.7
8.9
8.4
6.2
2.8
8.9
8.7
3
3
1iA: Major, S-β-trans
1iC: Minor, S-α-trans
High
Low
5.48
5.46
5.07
4.97
5.48
5.50
4.70
4.79
4.27
4.29
5.7
5.0
9.2
8.4
5.6
2.9
8.9
8.9
3
3
1jA: Major, S-β-trans
1jC: Minor, S-α-trans
High
Low
5.62
5.59
4.99
4.88
5.49
5.50
4.67
4.76
4.21
4.28
3.6
3.6
9.2
8.2
5.6
2.7
8.8
8.8
3
3
7A: Major, R-α-trans
7C: Minor, R-β-trans
High
Low
5.48
5.45
3.53
3.41
5.51
5.47
4.73
4.77
4.24
4.30
3.2
3.2
9.2
8.4
6.2
2.7
8.9
8.7
8
9
13D: Major, S-β-trans
-
5.40
4.98
5.45
4.71
4.25
5.2
9.0
5.5
8.8
13
Table 6: C NMR comparison of trans Nazarov products bearing the (S)-4-phenyloxazolidin-2-one auxiliary.
1
5
4
x
y
z
Entry Product
R
f
C (ppm) C (ppm) C (ppm) C (ppm) C (ppm) C (ppm)
3
3
1aA (minor)
1aC (major)
High
Low
199.9
201.1
56.6
56.0
45.5
46.5
168.4
168.8
58.4
58.1
69.7
69.8
1
2
3
4
5
3
3
1eA (minor)
1eC (major)
High
Low
191.8
193.2
55.4
54.6
40.1
41.7
168.1
168.6
58.7
58.1
69.8
69.9
3
3
1fA (minor)
1fC (major)
High
Low
197.6
198.7
60.1
59.6
40.5
41.5
168.0
168.3
58.4
58.1
69.8
69.9
3
3
1gA (major)
1gC (minor)
High
Low
199.7
200.9
60.5
59.9
51.0
52.0
167.4
167.9
58.3
58.4
69.7
70.0
3
3
1hA (major)
1hC (minor)
High
Low
191.6
192.8
58.9
58.3
45.7
47.0
167.1
167.7
58.5
58.0
69.8
70.0
3
3
1iA (major)
1iC (minor)
High
Low
196.9
198.1
64.0
63.4
46.0
47.2
166.9
167.6
58.3
58.3
69.8
70.1
6
7
3
3
1jA (major)
1jC (minor)
High
Low
181.9
183.0
67.2
66.6
41.4
42.4
167.9
168.3
58.5
58.2
69.7
69.9
3
3
7A (major)
7C (minor)
High
Low
182.7
183.8
61.4
60.8
43.7
44.7
169.1
169.3
58.5
58.1
69.7
69.8
8
9
13D (major)*
-
196.9
64.2
45.7
167.0
58.4
69.9
S-2

Table 7: NMR comparison of tigloyl-based trans-configured Nazarov products.
n
1
3
4
5
n
m
Entry
R
Product
R
f
H (δ)
C (δ)
C (δ)
C (δ) C (δ) C (δ) C (δ)
1
n-Pr
31aA (minor)
Higher 1.97
Lower 2.00
199.9
201.1
172.6
173.2
45.5
46.5
56.6
56.0
15.0
15.0
8.2
8.1
3
1aC (major)
2
3
4
5
6
n-Pr
n-Pr
n-Pr
Ph
31bA (minor)
Higher 2.04
Lower 2.05
200.7
201.4
172.7
173.3
45.9
46.4
56.4
55.7
15.0
15.0
8.2
8.1
3
1bC (major)
31cA (minor)
Higher 2.00
Lower 2.03
200.1
201.0
172.5
173.4
45.9
46.1
56.7
56.3
15.0
15.1
8.2
8.2
3
1cC (major)
31dA (minor)
Higher 2.05
Lower 2.07
200.7
201.0
172.0
173.2
46.9
46.4
56.0
56.0
15.0
15.1
8.2
8.2
3
1dC (major)
31gA (major)
Higher 1.79
Lower 1.83
199.7
200.9
170.8
171.9
51.0
52.0
60.5
59.9
15.3
15.5
8.5
8.5
3
1gC (minor)
Ph
31kA (major)
Higher 1.85
Lower 1.86
200.7
201.0
171.0
171.7
51.7
52.2
60.3
59.9
15.4
15.5
8.6
8.5
3
1kC (minor)
S-3

II. Extended Listing of Reaction Conditions used in the Cyclisation 30 to 31
Table 8: Nazarov Cyclisations of 30 to give 31.
1
a
Product, % amount by H NMR (isolated yield %)
Entry Substrate
Conditions
1.1 Eq. MeSO
MeSO H, A
Cu(OTf) , B
S-β-trans
31aA, 21
31aA, 26 (24)
31aA, 31
31aA, 9
S-β-cis
S-α-trans
31aC, 54
31aC, 74 (71)
31aC, 48
31aC, 19
31aC, 25
S-α-cis
exo-isomers
31aE, 25
31aE, 0
31aE, 21
31aE, 0
1
2
3
4
5
30a
30a
30a
30a
30a
3
H
-
-
-
-
-
-
3
-
-
-
-
2
b
FeCl
SnCl
3
, F
, G
b
4
31aA, 14
31aE, 2
6
7
8
30b
30c
30d
MeSO
MeSO
MeSO
3
H, A
3
H, A
3
H, A
31bA 22 (21)
31cA 28 (25)
31dA 24 (23)
-
-
-
31bC 78 (71)
31cC 72 (71)
31dC 76 (70)
-
-
-
-
-
-
9
30e
30e
2.0 Eq. MeSO
3
H
31eA, 32 (27)
31eA, 39
-
-
31eC, 68 (65)
31eC, 61
-
-
-
-
1
0
Cu(OTf)
2
, Reflux
c
1
1
30f
MeSO
3
H, A
31fA, 28 (26)
-
31fC, 46 (43)
31gC, 17
-
-
1
1
1
1
1
2
3
4
5
6
30g
30g
30g
30g
30g
MeSO
MeSO
Cu(OTf)
3
H, A
H, C
, B
0.1 Eq. Cu(OTf)
Cu(OTf) , toluene, 60 °C 31gA, 58
31gA, 31
31gA, 0
31gA, 60 (65)
31gB, 41
31gB, 63 (70) 31gC, 0
31gB, 8
31gB, 5
31gB, 4
31gD, 11
31gD, 24
31gD, 2
31gD, 4
31gD, 3
31gE, 0
d
3
31gE, 13
31gE, 14
31gE, 17
31gE, 17
d
2
31gC, 16 (10)
31gC, 18
31gC, 17
2
, Reflux 31gA, 56
2
1
1
7
8
30h
30h
MeSO
Cu(OTf)
3
H, C
, B
31hA, 7
31hA, 70 (48)
31hB, 68 (64) 31hC, 2
31hD, 23
31hD, 8
-
-
2
31hB, 9
31hC, 13 (8)
1
2
9
0
30i
30i
MeSO
3
H, A
31iA, 71 (68)
31iA, 18
31iB, 15
31iB, 0
31iC, 13 (5)
31iC, 0
31iD, 0
31iD, 0
-
-
c
Cu(OTf) , Reflux
2
2
2
1
2
30j
30j
MeSO H, C
31jA, 0
31jA, 56 (51)
31jB, 82 (81)
31jB, 18 (16)
31jC, 0
31jC, 22 (18)
31jD, 18 (10)
31jD, 4
-
-
3
Cu(OTf)
2
, Reflux
2
2
3
4
30k
30k
MeSO H, A
31kA, 40
31kA, 51 (50)
31kB, 14
31kB, 6
31kC, 23
31kC, 22 (23)
31kD, 16
31kD, 5
31kE, 7
31kE, 16
3
d
Cu(OTf)
unless stated otherwise, A: MeSO
(aq); C: MeSO H (10 equiv.), −78 °C to 0 °C, 0.5 – 2 h, then NaHCO
(1.1 equiv.), −78 °C to rt, 1 h, then NaHCO
2
, B
a
All reactions in CH
rt, 1-48 h, then NaHCO
NaHCO (aq); G: SnCl
2
Cl
2
3
H (5-10 equiv.), −78 °C to rt, 1-24 h, then NaHCO
(aq); F: FeCl
(aq). A significant amount of undiscerned product was observed in the H NMR of
3
(aq); B: Cu(OTf)
3
(1.1 equiv.), −78 °C to rt, 1 h, then
2
(1.1 equiv.), −78 °C to
3
3
3
b
1
3
4
3
c
1
d
the crude reaction mixture. Starting material 30 represented the majority of remaining product based on H NMR of the crude reaction mixture. Some
isomerisation of minor isomers during chromatography gives greater yield of isolated product.
S-4

III. Crystallographic data for 31aC and 31hA
Crystallography. Diffraction data for compound 31aC were recorded on an Enraf Nonius CAD4f diffractometer operating
1
2
3
in the /2 scan mode at 293 K. Data processing, absorption corrections, structure solution, and refinement were
4
implemented within the WingX suite of programs. Intensity data for 31hA were collected at 130 K with a Bruker SMART
5
Apex CCD detector using Mo-K radiation (graphite crystal monochromator  = 0.71073). Data were reduced using the
program SAINT and corrected for absorption (SADABS).
Crystal data for 31aC. C H NO , M = 341.39, T = 293(2) K, = 1.54180, Orthorhombic, space group P2 2 2 a = 7.793(2),
2
0
23
4
1 1 1
3
-3
-1
b = 13.870(3), c =16.681(5), Å, V 1803.0(8) Å , Z = 4, D
c
= 1.258 mg M (Cu-K) 0.710 mm , F(000) = 728, crystal size
3
2
0
.4 x 0.3 x 0.2 mm . 1971 reflections measured, 1971 independent reflections, the final R was 0.0467 [I > 2(I)] and wR(F )
was 0.1238 (all data). This data has been deposited at the Cambridge Crystallographic Data Centre (www.ccdc.cam.ac.uk),
depository number: 793956
Figure A: X-Ray crystal structure of 31aC (ORTEP, numbering different to main text).
Crystal data for 31hA. C24
H
21 N O
5
, M = 403.42, T = 130(2) K, = 0.71073, Monoclinic, space group P2
1
a = 9.483(2), b =
3
-3
2
2.611(5), c =10.386(2), Å,= 114.551(4), V 2025.5(8) Å , Z = 4 (two molecules in asymmetric unit), D
(Mo-K) 0.093 mm , F(000) = 848, crystal size 0.45 x 0.40 x 0.35 mm . 16944 reflections measured, 8789 independent
c
= 1.323 mg M
-
1
3

2
reflections (Rint = 0.0249), the final R was 0.0515 [I > 2(I)] and wR(F ) was 0.1281 (all data). This data has been deposited
at the Cambridge Crystallographic Data Centre (www.ccdc.cam.ac.uk), depository number: 793957
Figure B: X-Ray crystal structure 31hA (ORTEP, numbering different to main text).
1
A. L. Spek, 'PLATON for windows. A Program for Absorption Corrections' University of Utrecht, The Netherlands, 1999.
G. M. Sheldrick, 'SHELXS-86; Crystallographic Computing 3', University of Göttingen, Germany, 1986.
G. M. Sheldrick, 'SHELXL-97; A Program for the Refinement of Crystal Structures' University of Göttingen, Germany, 1997.
L. J. Farrugia, J. Appl. Crystallogr., 1999, 32, 837.
2
3
4
5
Siemens 1999, SMART, SAINT, SADABS, Siemens Analytical X-ray Instruments Inc. Madison, Wisconsin, USA.
S-5

Experimental Details
General Experimental Details
General: All experiments were performed under an anhydrous atmosphere of nitrogen in flame-dried glassware except as
indicated. All reaction products were stored in sealed (parafilm) pre-dried vials under an anhydrous atmosphere of nitrogen.
1
Melting points were recorded with an Electrothermal melting point apparatus and are uncorrected. Proton ( H) and carbon
1
3
(
(
C) NMR spectra were recorded at 300 MHz for proton and 75 MHz for carbon nuclei. All NMR spectra were recorded in
D)chloroform (CDCl ) at 30 °C. The protonicities of the carbon atoms observed in the carbon NMR were determined using
3
J-modulated spin-echo (JMOD) experiments or APT. Infrared spectra (IR) were obtained on FT-IR spectrometer. Low-
resolution mass spectra (LRMS) were recorded on a quadrupole spectrometer using electrospray ionisation (ESI). High-
resolution mass spectra (HRMS) were recorded on a time of flight mass spectrometer fitted with either an electrospray (ESI)
or atmospheric pressure ionization (APCI) ion source. Tetrahydrofuran and diethyl ether were distilled under nitrogen from
sodium benzophenone ketyl. Dichloromethane and 1,2-dichloroethane were distilled from calcium hydride under nitrogen.
Analytical thin layer chromatography (TLC) was conducted on aluminium sheets coated with silica gel 60 GF . Flash
254
chromatography was performed on flash grade silica gel. Experimental methods for the following compounds has been
previously reported: 16f-i and 17f-i are reported in reference 7 of the main text.
General Procedure A: Reductive-Coupling of 14 (or 29) and 15 to form 16 (or 30).
Pd(PPh
0.12 mmol) in THF followed by stirring for 0.5 h at 18 °C. To this solution alkyne 14 or 29 (1.0 mmol) was added, followed
by dropwise addition of Bu SnH (1.05 mmol) and then the reaction was left to stir for 10-30 min. Organic halide 15 (1.1
3 4 2 3
) (0.03 mmol) was added to THF (7 mL) or generated in situ by addition Pd(dba) (3 mol%) to a solution of PPh
(
3
mmol) and CuCl (0.8 mmol) were then added and the reaction stirred at 18 °C for 5-30h, monitoring consumption of
intermediate alkenyl stananne by TLC (silica). KF(aq) (30%, 20 mL) was added and the reaction stirred for 2 h. The triphasic
(
organic, aqueous and solid) mixture was filtered through celite, washing with ethyl acetate (25 mL). The aqueous phase was
separated from organic phase and further extracted with ethyl acetate (25mL). The combined organic extracts were dried over
MgSO and concentrated onto silica gel (1 g) under reduced pressure. The solid residue was subjected to flash
4
chromatography (silica gel) to provide the product (16 or 30).
Methyl 2-(5,5-dimethyl-3-oxo-cyclohex-1-enyl)-acrylate (16a)
6
Alkyne 14a was reacted with 3-bromo-5,5-dimethyl-2-cyclohexenone (15a) in accordance with General Procedure A, giving
the product 16a after flash chromatography (silica gel, hexanes / dichloromethane / diethyl ether 6:2:1) as a clear oil (61%).
1
The H NMR of the crude reaction mixture indicated almost quantitative conversion of 14a to 16a, however, the product is
1
unstable and the isolated material decomposed at 4 °C over several days. H NMR (300 MHz, CDCl
3
) δ 6.25 (s, 1H), 6.16 (t,
13
J = 1.6 Hz, 1H), 5.86 (s, 1H), 3.81 (s, 3H), 2.39 (d, J = 1.6 Hz, 2H), 2.29 (s, 2H), 1.08 (s, 6H). C NMR (JMOD, 75 MHz,
CDCl ) δ 199.7 (C), 165.6 (C), 154.3 (C), 141.2 (C), 127.1 (CH ), 126.9 (CH), 52.0 (CH ), 50.8 (CH ), 41.7 (CH ), 33.6 (C),
). IR (NaCl film, cm ): 2957, 2870, 1726, 1668, 1437, 1369, 1297, 1198, 1158, 994, 906. LRMS (70 eV) m/z (%):
3
2
3
2
2
−
1
2
2
7.9 (CH
3

08 ( , 65), 133 (65), 124 (100), 105 (80), 91 (60). HRMS calcd for C H O : 208.1099. Found: 208.1099.
1
2
16
3
Methyl (Z)-2-(4-methoxyphenyl)-3-phenyl-acrylate (16b)
Alkyne 14b was reacted with 4-iodoanisole (15b) in accordance with General Procedure A, giving the product 16b after flash
1
chromatography (silica gel, hexanes / diethyl ether 9:1) as a slightly tan oil (75%). H NMR (300 MHz, CDCl
8
3
) δ 7.33 (d, J =
1
3
.3 Hz, 2H), 7.30-7.20 (m, 5H), 6.89 (s, 1H), 6.84 (d, J = 8.3 Hz, 2H), 3.75 (s, 3H), 3.71 (s, 3H). C NMR (JMOD, 75 MHz,
3
CDCl ) δ 170.3 (C), 159.7 (C), 135.8 (C), 134.3 (C), 129.5 (CH), 129.3 (C), 128.4 (CH), 128.0 (CH), 127.9 (CH), 127.6
6
Piers, E.; Grierson, J. R.; Lau, C. K.; Nagakura, I. Can. J. Chem. 1982, 60, 210.
S-6

−
1
(
CH), 114.0 (CH), 55.2 (CH ), 52.1 (CH ). IR (NaCl film, cm ): 3025, 2952, 2839, 1727, 1606, 1513, 1288, 1249, 1033.
3 3


7
LRMS (70 eV) m/z (%): 268 ( , 100), 209 (55), 165 (55), 121 (85), 84 (65). Known compound.
Methyl (Z)/(E)-2-(5,5-Dimethyl-3-oxo-cyclohex-1-enyl)-3-phenyl-acrylate (16c)
Alkyne 14b was reacted with 3-bromo-5,5-dimethyl-2-cyclohexenone (15a) in accordance with General Procedure A giving
the product 16c after flash chromatography (silica gel, hexanes / dichloromethane / diethyl ether 9:3:1) giving the product as
1
separable (E/Z)-isomers of 16c (93%). Higher R
3
f
isomer Z-16c, (22%, thick oil) H NMR (300 MHz, CDCl
3
) δ7.40-7.30 (m
1
3
H), 7.12-7.04 (m, 2H), 6.31 (s, 1H), 5.83 (s, 1H), 3.57 (s, 3H), 2.42 (s, 2H), 2.28 (s, 2H), 1.08 (s, 6H). C NMR (JMOD, 75
MHz, CDCl ) δ200.0 (C), 165.8 (C), 156.1 (C), 155.1 (C), 136.2 (C), 130.5 (CH), 128.4 (CH), 128.3 (CH), 128.1 (CH),
3
−1
1
1
2
3 2 2 3
20.3 (CH), 51.6 (CH ), 51.0 (CH ), 40.6 (CH ), 33.6 (C), 28.3 (CH ). IR (NaCl film, cm ): 3080, 3057, 3026, 2957, 2870,


731, 1668, 1613, 1590, 1434, 1307, 1276, 1236, 1167, 1118, 1018, 700. LRMS (70 eV) m/z (%): 284 ( , 100), 237 (85),
1
25 (80), 209 (80), 199 (80), 141 (70). Lower R
f
isomer E-16c, (71%, white solid). Mp = 77-9 C. H NMR (300 MHz,
1
3
CDCl
3
)  7.35 (s, 5H), 7.04 (s, 1H), 6.03 (s, 1H), 3.78 (s, 3H), 2.48 (s, 2H), 2.31 (s, 2H), 1.12 (s, 6H). C NMR (JMOD, 75
)  199.5 (C), 168.6 (C), 151.6 (C), 134.9 (C), 134.2 (C), 133.8 (CH), 129.3 (CH), 128.6 (CH), 128.4 (CH),
MHz, CDCl
3
-
1
1
1
8
25.5 (CH), 52.3 (CH ), 50.7 (CH ), 39.4 (CH ), 33.1 (C), 28.3 (CH ). IR (KBr disc, cm ): 3047, 2955, 2929, 2871, 1725,
3 2 2 3


673, 1581, 1465, 1440, 1305, 1277, 1261, 1236, 1219, 1161, 1111, 1003, 759, 688, 520. LRMS (70 eV) m/z (%): 284 ( ,
5), 225 (90), 209 (80), 196 (75), 141 (100). HRMS calcd for C H O : 284.1412. Found: 284.1417.
1
8
20
3
Methyl (Z)-2-benzylidine-4-pentenoate (16d)
Alkyne 14b was reacted with allylbromide (15c) in accordance with General Procedure A giving the product 16d after flash
1
chromatography (silica gel, hexanes / diethyl ether 39:1) as a clear oil (83%). H NMR (300 MHz, CDCl
3
)  7.45-7.20 (m,
5
3
1
1
H), 6.68 (s, 1H), 5.89 (ddt, J = 17.0, 10.2, 6.6 Hz, 1H), 5.17 (d, J = 17.0 Hz, 1H), 5.13 (d, J = 10.2 Hz, 1H), 3.64 (s, 3H),
1
3
.17 (d, J = 6.6 Hz, 2H). C NMR (JMOD, 75 MHz, CDCl
28.1 (CH), 128.0 (CH), 127.8 (CH), 117.4 (CH ), 51.6 (CH
720, 1435, 1215, 1123, 922, 752, 696. LRMS (70 eV) m/z (%): 202 ( , 60), 143 (100).
3
)  169.8 (C), 136.0 (C), 134.5 (CH), 134.2 (CH), 132.5 (C),
−1
2
3 2
), 39.2 (CH ). IR (NaCl film, cm ): 3081, 3061, 3027, 2951,


Methyl (Z)/(E)-3-phenyl-2-(3,4,5-trimethoxybenzoyl)-acrylate (16e)
Alkyne 14b was reacted with 3,4,5-trimethoxybenzoyl chloride (15d) in accordance with General Procedure A giving the
product 16e after flash chromatography (silica gel, hexanes / dichloromethane / diethyl ether 10:10:1) as a slightly yellow
solid (70%). Mp 69-70 C. This material was identified as being the (E)-isomer, a small amount of (Z)-isomer was also
1
isolated (yield not determined). Z-16e: H NMR (300 MHz, CDCl
3
) δ 7.20-7.50 (m, 6H), 7.08 (s, 2H), 3.93 (s, 3H), 3.88 (s,
1
6
6
H), 3.79 (s, 3H). E-16e: H NMR (300 MHz, CDCl
H), 3.78 (s, 3H). C NMR (JMOD, 75 MHz, CDCl ) δ 193.8 (C), 165.1 (C), 152.9 (C), 143.0 (C), 142.4 (CH), 132.5 (C),
3
)  7.99 (s, 1H), 7.40-7.25 (m, 5H), 7.19 (s, 2H), 3.90 (s, 3H), 3.82 (s,
1
3
3
1
30.6 (C), 130.3 (C), 130.2 (CH), 129.8 (CH), 128.5 (CH), 106.2 (CH), 60.5 (CH ), 55.9 (CH ), 52.3 (CH ). IR (KBr disc,
3
3
3
−1
cm ): 3089, 3061, 3001, 2947, 2836, 1712, 1663, 1619, 1581, 1501, 1329, 1255, 1128, 1000. LRMS (70 eV) m/z (%): 356


( ,90), 195 (100), 121 (35), 84 (40). HRMS calcd for C20
20 6
H O : 356.1260. Found: 356.1258.
7
Cacchi, S.; Fabrizi, G; Moro, L.; Pace, P.; Synlett 1997, 1367.
S-7

(±)-Methyl trans-4,5,6-trimethoxy-1-oxo-3-phenyl-2,3-dihydro-1H-indene-2-carboxylate (17e)
Methanesulfonic acid (110 L, 1.66 mmol) was added to a solution of propenoate 16a (130 mg, 0.365 mmol) in dry
dichloromethane (2 mL). After stirring for 2 h the solution was diluted with diethyl ether (10 mL), washed with distilled
water (5 mL), dried over MgSO
dichloromethane / diethyl ether) returned the desired material 8f as a discoloured oil (108 mg, 84 %). H NMR (300 MHz,
CDCl )  7.30-7.15 (m, 3H), 7.15-7.05 (m, 2H), 7.08 (s, 1H), 4.94 (d, J = 3.2 Hz, 1H), 3.90 (2  s, 6H), 3.77 (s, 3H), 3.62 (d,
J = 3.2 Hz, 1H), 3.33 (s, 3H). C NMR (JMOD, 75 MHz, CDCl
43.4 (C), 142.5 (C), 130.3 (C), 128.7 (CH), 127.3 (CH), 127.0 (CH), 100.9 (CH), 63.5 (CH), 60.8 (CH
4
and concentrated onto silica gel (~1 g). Flash chromatography (14:14:1, hexanes /
1
3
1
3
3
)  197.7 (C), 168.7 (C), 155.1 (C), 150.2 (C), 149.4 (C),
), 59.9 (CH ), 56.2
3
), 46.1 (CH). IR (KBr film, cm ): 3084, 3059, 3028, 2952, 2852, 1741, 1710, 1661, 1572, 1471, 1434,
1
3
3
−1
(
CH
3
), 52.8 (CH
345, 1313, 1267, 1191, 1126, 1065, 1030, 1004, 966, 841, 702, 559. LRMS (70 eV) m/z (%): 356 (  85), 324 (40), 296
: 356.1260. Found: 356.1263.


1
(
100). HRMS calcd for C20
H
20
O
6
3
-Phenyl-2-(3, 4, 5-trimethoxybenzoyl)-2-propenal (16j)
Alkyne 14d was reacted with 15d in accordance with General Procedure A giving the product 16j after flash chromatography
silica gel, hexanes / dichloromethane / diethyl ether 20:20:3) giving the product 16j as a lightly discolored solid (48%). Mp =
(
1
1
00-2 °C. H NMR (300 MHz, CDCl
3
) δ 9.73 (s, 1H), 7.59 (s, 1H), 7.45-7.25 (m, 5H), 7.15 (s, 2H), 3.88 (s, 3H), 3.79 (s, 6H).
1
3
C NMR (JMOD, 75 MHz, CDCl
CH), 130.6 (CH), 129.1 (CH), 106.6 (CH), 60.9 (CH
3
)  194.4 (C), 191.2 (CH), 153.3 (C), 150.1 (CH), 143.7 (C), 140.3 (C), 132.4 (C), 131.6
−1
(
3
), 56.2 (CH
645, 1609, 1580, 1499, 1466, 1413, 1373, 1331, 1234, 1208, 1127, 1000, 860, 761, 684. LRMS (70 eV) m/z (%): 326 ( ,
00), 298 (90), 283 (50), 195 (70). HRMS calcd for C19 : 326.1154. Found: 326.1155.
3
). IR (KBr disc, cm ): 3089, 3014, 2941, 2841, 1678,


1
1
18 5
H O
Methyl (2Z,4E)/(2Z,4E)-2-benzylidene-4-methyl-3-oxohex-4-enoate (16k).
Alkyne 14b was reacted with 15g in accordance with General Procedure A giving the product 16k after flash chromatography
(
silica gel, hexanes / diethyl ether 4:1) as a slightly tan oil (87%). Proton NMR analysis revealed 91% isomeric purity
1
predominately the E,Z-isomer: H NMR (300 MHz, CDCl
3
)  7.45-7.30 (m, 5H), 7.21 (s, 1H), 6.62 (q, J = 6.7, Hz, 1H), 3.77
(
s, 3H), 2.89 (s, 3H), 2.88 (d, J = 6.7 Hz, 3H). On standing at ~4 C for 72 h the (Z,E)-isomer converted completely to the
1
(E,E)-isomer: H NMR (300 MHz, CDCl
3
)  7.80 (s, 1H), 7.35-7.28 (m, 5H), 6.72 (q, J = 6.7 Hz, 1H), 3.79 (s, 3H), 1.90 (s,
H), 1.78 (d, J = 6.7 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl )  197.0 (C), 165.5 (C), 142.9 (CH), 141.6 (CH), 138.1 (C),
33.0 (C), 131.2 (C), 130.0 (CH), 129.8 (CH), 128.6 (CH), 52.3 (CH ), 14.9 (CH ), 10.4 (CH ). IR (NaCl film, cm ): 3056,
13
3
1
3
3
−1
3
3
3
028, 3000, 2952, 1715 (2 peaks), 1640 (multiple peaks), 1575, 1496, 1434, 1258, 1200. LRMS (70 eV) m/z (%): 244


16 3
( 85), 211 (65), 185 (65), 121 (70), 83 (100). HRMS calcd for C15H O : 244.1099. Found: 244.1098.
(±)-Methyl trans-3,4-dimethyl-2-oxo-5-phenylcyclopent-3-enecarboxylate (17k)
Methanesulfonic acid (16 L, 0.24 mmol) was added to a solution of 16k (48.9 mg, 0.200 mmol) in dry dichloromethane (7
mL). After stirring for 4 h the solution was diluted with diethyl ether (20 mL), washed with distilled water (20 mL), dried
over MgSO
4
and concentrated under reduced pressure to give 17k as a slightly discolored solid (44.1 mg, 90%) Mp = 70-2
S-8

1
°
3
1
C. H NMR (300 MHz, CDCl ) δ 7.40-7.20 (m, 3H), 7.09 (dd, J = 6.4, 3.0 Hz, 2H), 4.23 (d, J = 2.7 Hz, 1H), 3.76 (s, 3H),
3
1
3
.39 (d, J = 2.7 Hz, 1H), 1.87 (s, 3H), 1.81 (s, 3H). C NMR (JMOD, 75 MHz, CDCl
40.1 (C), 135.4 (C), 129.1 (CH), 127.5 (CH), 60.9 (CH), 53.0 (CH or CH), 52.7 (CH
3
) δ 201.4 (C), 171.8 (C), 169.1 (C),
3
3
or CH), 15.6 (CH
3
), 8.5 (CH
3
). IR
−
1

(
KBr disc, cm ): 3029, 2951, 1735, 1702, 1645, 1599, 1494, 1433, 1162, 1031, 767, 700. LRMS (70 eV) m/z (%): 244 ( ,
7
5), 184 (100), 141 (35). HRMS calcd for C H O : 244.1099. Found: 244.1101.
15 16 3
Methyl (2Z,4E)/(2E,4E)-5-(benzo[d][1,3]dioxol-5-yl)-2-benzylidene-3-oxopent-4-enoate (16l)
Alkyne 14b was reacted with 15h in accordance with General Procedure A giving the product 16l after flash chromatography
flash chromatography (silica gel, hexanes / dichloromethane / diethyl ether 10:10:1) as a yellow solid (72%, mixture of (Z,E)-
and (E,E)-isomers). Crystallization of this material from minimal dichloromethane with hexanes gave Z-16l (414 mg, 41%),
1
the remaining material contains roughly equal proportions of both isomers. Z-16l: H NMR (300 MHz, CDCl
3
) δ7.72 (d, J =
1
7
5.4 Hz, 1H), 7.72 (s, 1H), 7.50-7.36 (m, 5H), 7.11 (s, 1H), 7.10 (d, J = 7.9 Hz, 1H), 7.00 (d, J = 15.4 Hz, 1H), 6.84 (d, J =


.9 Hz, 1H), 6.03 (s, 2H), 3.87 (s, 3H). LRMS (70 eV) m/z (%): 336 ( , 100), 277 (75), 175 (95), 145 (65), 89 (75).
Complete conversion to the (E,E)-Isomer E-16l was observed after storing the material at 4C for 6 months). Mp = 121-3 C.
1
H NMR (300 MHz, CDCl ) δ7.89 (s, 1H), 7.48-7.22 (m, 6H), 6.99 (s, 1H), 6.95 (d, J = 8.4 Hz, 1H), 6.78 (d, J = 8.4 Hz,
3
1
3
1
H), 6.67 (d, J = 16.1 Hz, 1H), 6.00 (s, 2H), 3.82 (s 3H). C NMR (150 MHz, CDCl
3
) δ 195.4 (C), 165.6 (C), 150.3 (C),
1
48.4 (C), 146.4 (CH), 142.5 (CH), 132.8 (C), 131.2 (C), 130.5 (CH), 130.2 (CH), 128.8 (CH), 128.5 (C), 125.6 (CH), 125.0
−1
(
2 3
CH), 108.6 (CH), 106.7 (CH), 101.7 (CH ), 52.7 (CH ). IR (KBr disc, cm ): 3070, 3015, 2949, 2903, 1718, 1642, 1601,


1
3
16 5
493, 1363, 1258. LRMS (70 eV) m/z (%): 336 ( , 95), 277 (75), 175 (100), 145 (65), 89 (80). HRMS calcd for C20H O :
36.0998. Found: 336.0994.
Methyl (Z)/(E)-2-[(E)-2-methylbut-2-enoyl]hex-2-enoate (16m)
Alkyne 14e was reacted with 15g in accordance with General Procedure A giving the product 16m after flash
1
chromatography flash chromatography (silica gel, hexanes / diethyl ether 8:1) as a clear oil (80%). Z-16m: H NMR (300
3
MHz, CDCl ) δ 6.51 (q, J = 7.1 Hz, 1H), 6.31 (t, J = 7.7 Hz, 1H), 3.69 (s, 3H), 2.49 (q, J = 7.7 Hz, 2H), 1.82 (d, J = 7.1 Hz,
1
3
3
1
H), 1.83 (s, 3H), 1.49 (sextet, J = 7.7 Hz, 2H), 0.93 (t, J = 7.7 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl ) δ 195.4 (C),
3
65.7 (C), 149.1 (CH), 140.7 (CH), 138.2 (C), 134.0 (C), 51.7 (CH
3
), 31.2 (CH
2
), 21.9 (CH
2
), 14.7 (CH
3
3
), 13.7 (CH ), 11.3
−
1
(
CH
3
). IR (NaCl film, cm ): 2958, 2932, 2871, 1726, 1659, 1642, 1434, 1215, 1158. After standing at 4 °C for 18 months
7
0% of the initially isolated Z-16m had converted to the more stable E-16m, this was purified by flash chromatography
1
(
3
silica gel, hexanes / diethyl ether 8:1). H NMR (300 MHz, CDCl ) δ 7.00 (t, J = 7.8 Hz, 1H), 6.64 (m, 1H), 3.71 (s, 3H),
1
3
2
.01 (dt, J = 7.8, 7.4 Hz, 2H), 1.90-1.80 (m, 6H), 1.45 (sextet, J = 7.4 Hz, 2H), 0.90 (t, J = 7.4 Hz, 3H). C NMR (JMOD, 75
) δ 196.0 (C), 165.0 (C), 146.6 (CH), 142.8 (CH), 138.8 (C), 133.4 (C), 51.9 (CH ), 31.4 (CH ), 21.5 (CH ), 14.9
). IR (NaCl film, cm ): 2961, 2932, 2874, 1725, 1660, 1642, 1435, 1281, 1247, 1226, 1054,
MHz, CDCl
CH ), 13.6 (CH
030. LRMS (70 eV) m/z (%): 210 ( , 5), 163 (55), 135 (60), 83 (100), 55 (90). HRMS calcd for C12
Found: 210.1258.
3
3
2
2
−1
(
3
3 3
), 10.2 (CH


1
18 3
H O : 210.1256.
(±)-Methyl trans-3,4-dimethyl-2-oxo-5-propylcyclopent-3-enecarboxylate (17m)
S-9

Methanesulfonic acid (36 L, 0.55 mmol) was added to a solution of 16m (105 mg, 0.500 mmol) in dry dichloromethane (7
mL). After stirring for 24 h the solution was diluted with diethyl ether (10 mL), washed with distilled water (5 mL), dried
over MgSO
4
and concentrated onto silica gel (0.5 g). Flash chromatography (silica gel, hexanes / diethyl ether 4:1) returned
1
1
7m as a clear oil (92.6 mg, 88%). H NMR (300 MHz, CDCl
3
)  3.74 (s, 3H), 3.08 (d, J = 2.6 Hz, 1H), 3.02 (br. s, 1H), 2.03
, 1H), 1.69 (s, 3H), 1.42-1.15 (m, 3H), 0.92 (t, J = 7.1 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl )  201.5
c 3
1
3
(
(
(
(
s, 3H), 1.78 (m
C), 173.3 (C), 170.2 (C), 134.7 (C), 57.3 (CH), 52.5 (CH
3
), 47.2 (CH), 34.3 (CH
2
), 20.3 (CH
2
), 15.2 (CH
3
), 14.0 (CH
3
), 8.3
−
1

CH
3
). IR (NaCl film, cm ): 2955, 2929, 2872, 1739, 1702, 1647, 1434, 1158. LRMS (70 eV) m/z (%): 210 ( , 80), 179
50), 150 (85), 122 (100). HRMS calcd for C12
18 3
H O : 210.1256. Found: 210.1255.
Methyl 4-(3-methoxyphenoxy)-2-butynoate (14f)
n-BuLi (2 M in cyclohexane, 3.10 mL, 6.2 mmol) was added dropwise to 3-methoxyphenyl propargyl ether (1.0 g, 6.17
8
mmol) in THF (11 mL) at -78 °C. After stirring at this temperature for 15 min, methylchloroformate (0.54 mL, 7.00 mmol)
was added and the reaction mixture brought to room temperature. Silica gel (5 g) was added and the solvent removed under
reduced pressure. The residue was subject to flash chromatography (silica gel, hexanes / diethyl ether 1:1) giving the product
1
as a colorless oil (1.17 g, 91%). H NMR (300 MHz, CDCl
3
) δ 7.20 (t, J = 8.1 Hz, 1H), 6.59-6.50 (m, 3H), 4.78 (s, 2H), 3.78
1
3
(
s, 3H), 3.76 (s, 3H). C NMR (JMOD, 75 MHz, CDCl
CH), 101.3 (CH), 82.0 (C), 78.2 (C), 55.3 (CH ), 55.2 (CH ), 52.7 (CH ). Known compound.
3
) δ160.7 (C), 158.3 (C), 153.2 (C), 129.9 (CH), 107.5 (CH), 106.5
9
(
2
3
3
Methyl (2Z,4E)-2-[2-(3-methoxyphenoxy)ethylidene]-4-methyl-3-oxohex-4-enoate (16n)
Alkyne 14f was reacted with 15g in accordance with General Procedure A giving the product 16n after flash chromatography
1
(
silica gel, hexanes / dichloromethane / diethyl ether 5:5:1) as a slightly tan oil (85%). Z-16n H NMR (300 MHz, CDCl
3
) δ
7
.18 (t, J = 8.1 Hz, 1H), 6.64 (q, J = 6.6 Hz, 1H), 6.55-6.42 (m, 4H), 5.11 (d, J = 4.5 Hz, 1H), 3.77 (s, 3H), 3.76 (s, 3H), 1.86
1
3
(
(
(
d, J = 6.6 Hz, 3H), 1.85 (s, 3H). C NMR (JMOD, 75 MHz, CDCl
CH), 143.4 (CH), 138.1 (C), 132.9 (C), 129.9 (CH), 106.7 (CH), 106.6 (CH), 101.2 (CH), 65.8 (CH
CH
3
) δ 194.2 (C), 164.8 (C), 160.8 (C), 159.0 (C), 145.7
), 55.2 (CH ), 52.2
2
3
−1
3
), 15.0 (CH
3
), 10.9 (CH
3
). IR (KBr film, cm ): 3000, 2953, 2838, 1722, 1658, 1603, 1492, 1437, 1377, 1334, 1263,

+

1
3
200, 1152. LRMS (FAB) m/z (%): 305 ( , 100), 273 (M+H MeOH, 60). HRMS (FAB) calcd for C17
21
H O
5
( :
05.1389 Found: 305.1392. Storage of this material at room temperature for extended periods (3-5 days) results in partial
isomerization to give some of the (E,E)-isomer. This mixture was separated and the (E,E)-isomer characterized
1
spectroscopically. E-16n: H NMR (300 MHz, CDCl
3
) δ 7.19-7.12 (m, 2H), 6.63 (q, J = 6.6 Hz, 1H), 6.52 (dd, J = 8.1 Hz, J
=
2.7 Hz, 1H), 6.41-6.35 (m, 2H), 4.56 (d, J = 5.4 Hz, 1H), 3.78 (s, 3H), 3.75 (s, 3H), 1.87 (s, 3H), 1.84 (d, J = 6.6 Hz, 3H).
1
3
C NMR (JMOD, 75 MHz, CDCl
3
) δ 194.9 (C), 164.5 (C), 160.8 (C), 159.1 (C), 143.4 (CH), 140.9 (CH), 138.6 (C), 134.8
), 55.3 (CH ), 52.5 (CH ), 15.1 (CH ), 10.5 (CH ). IR (KBr
(
C), 130.0 (CH), 106.9 (CH), 106.2 (CH), 101.1 (CH), 64.6 (CH
2
3
3
3
3
−1
film, cm ): 2953, 1723, 1658, 1603, 1492, 1436, 1247, 1199, 1153.
1
-Benzyl-1H-pyrrole-2-carbonyl chloride (15i)
Trichloroacetyl chloride (4.3 mL, 38 mmol) was added slowly to a stirred solution of N-benzylpyrrole (5.0 g, 31.8 mmol) in
dry diethyl ether (80 mL). The reaction was allowed to stir for 24 hours before being concentrated under reduced pressure.
8
Tsutomu, I; Keiko, N.; Naoko, O.; Hisashi, I. Heterocycles 1994, 39, 371.
Pastine, S. J.; Youn, S. W.; Sames, D. Tetrahedron 2003, 59, 8859.
9
S-10

The solid residue was dissolved in ethanol (95%, 160 mL) and aqueous sodium hydroxide (4.0 M, 30 mL, 120 mmol) was
added. This solution was refluxed for 5 hours before being reduced in volume to 40 mL under reduced pressure. Diethyl ether
(
60 mL) and distilled water (50 mL) were added and the aqueous phase was collected, the organic phase was extracted with
more distilled water (25 mL) and the combined aqueous extracts were acidified to pH 2 with 5 M hydrochloric acid. This
mixture was extracted with diethyl ether (2 × 30 mL) and the organic extracts were dried over magnesium sulphate and
concentrated under reduced pressure to give the crude acid that was used without further purification.
Thionyl chloride (23.5 mL, 318 mmol) was added to the above crude acid in dry diethyl ether (160 mL) and the
resultant solution was stirred for 4 hours. After this time the solution was concentrated under reduced pressure to give the title
1
compound as a dark solid (6.28 g, 90%). H NMR (300 MHz, CDCl
3
) 7.40-7.25 (m, 4H), 7.15-7.05 (m, 3H), 6.27 (dd, J =
1
3
4
.4 Hz, 2.6 Hz, 1H), 5.43 (s, 2H). C NMR (JMOD, 75 MHz, CDCl
CH), 127.3 (CH), 127.2 (CH), 124.7 (C), 110.4 (CH), 52.9 (CH ). Known compound.
3
) δ 157.2 (C), 136.7 (C), 133.8 (CH), 128.9 (CH), 128.1
1
0
(
2
Ethyl (Z)/(E)-2-(1-benzyl-1H-pyrrole-2-carbonyl)-4-methylpent-2-enoate (16o).
Alkyne 14g was reacted with 15i in accordance with General Procedure A giving the product 16o after flash chromatography
1
(
silica gel, 9:1 hexane / diethyl ether) as a tan oil (82%). Z-16o H NMR (300 MHz, CDCl
3
) δ 7.33-7.20 (m, 3H), 7.15 (d, J =
.2 Hz, 2H), 6.95 (dd, J = 2.6, 1.7 Hz, 1H), 6.82 (dd, J = 4.1, 1.7 Hz, 1H), 6.32 (d, J = 9.9 Hz, 1H), 6.18 (dd, J = 4.1, 2.6 Hz,
H), 5.60 (s, 2H), 4.19 (q, J = 7.2 Hz, 2H), 3.21 (dsept, J = 9.9, 6.6 Hz, 1H), 1.20 (t, J = 7.2 Hz, 3H), 1.10 (d, J = 6.6 Hz, 6H).
7
1
1
3
C NMR (JMOD, 75 MHz, CDCl
3
) δ 182.8 (C), 165.6 (C), 154.4 (CH), 138.0 (C), 133.2 (C), 131.0 (CH), 130.0 (C), 128.5
), 52.3 (CH ), 28.6 (CH), 22.0 (CH ), 13.9 (CH ). LRMS
), 326.2 (100, MH ). HRMS calcd for C20 : 348.1576.
(
CH), 127.4 (CH), 127.2 (CH), 122.1 (CH), 108.8 (CH), 61.0 (CH
2
2
3
3
+
4
+
+
+
m/z (%): 668.6 (10, 2×M+NH
), 343.2 (10, M+ NH
4
H23NNaO
3
−1
Found: 348.1575. IR (cm ): 3031, 2964, 1718, 1634, 1465, 1407, 1216, 1084, 712. This material isomerised to the E-isomer
upon standing. E-16o: H NMR (300 MHz, CDCl ) δ 7.33-7.23 (m, 3H), 7.13 (d, J = 6.3 Hz, 2H), 6.99 (dd, J = 2.4, 1.5 Hz,
1
3
1
2
H), 6.79 (dd, J = 3.9, 1.5 Hz, 1H), 6.76 (d, J = 11.1 Hz, 1H), 6.18 (dd, J = 3.9, 2.4 Hz, 1H), 5.66 (s, 2H), 4.14 (q, J = 7.2 Hz,
H), 2.29 (dsept, J = 11.1, 6.6 Hz, 1H), 1.15 (t, J = 7.2 Hz, 3H), 0.93 (d, J = 6.6 Hz, 6H).
()-Ethyl trans-1-benzyl-4-isopropyl-6-oxo-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-5-carboxylate (17o).
Methanesulfonic acid (1.10 mL, 16.6 mmol) was added dropwise to a stirred solution of 16o (1.08 g, 3.31 mmol) in
dichloromethane (13 mL) at room temperature and the mixture was stirred for 2 hours. After this time the acid was quenched
by gradual addition of sodium bicarbonate solution (5% w/v, 60 mL). After stirring for 1 hour the mixture was diluted with
dichloromethane (40 mL) and the organic phase was separated, the aqueous phase was then extracted with dichloromethane
(
2 × 20 mL). The combined organic extracts were dried over MgSO and concentrated to give the title compound 17o as a
4
1
discoloured solid (1.08 g, 100%). Mp = 68-69 °C. H NMR (300 MHz, CDCl
3
) 7.37-7.20 (m, 5H), 6.99 (d, J = 2.1 Hz, 1H),
6
1
.10 (d, J = 2.1 Hz, 1H), 5.33-5.17 (m, 2H), 4.24 (q, J = 7.1 Hz, 2H), 3.57 (d, J = 2.4 Hz, 1H), 3.33 (dd, J = 6.3, 2.4 Hz, 1H),
1
3
.93 (app. octet, Japp = 6.7 Hz, 1H), 1.30 (t, J = 7.1 Hz, 3H), 0.99 (d, J = 6.0 Hz, 3H), 0.97 (d, J = 5.1 Hz, 3H). C NMR
) 184.1 (C), 170.3 (C), 153.9 (C), 136.8 (C), 134.7 (CH), 132.5 (C), 128.7 (CH), 127.9 (CH), 127.8
CH), 106.4 (CH), 62.9 (CH), 61.1 (CH ), 50.8 (CH ), 45.4 (CH), 31.8 (CH), 20.1 (CH ), 19.7 (CH ), 14.1 (CH ). LRMS m/z
%): 668.6 (25, 2×M+NH ), 343.2 (10, M+ NH ), 326.2 (100, MH ). HRMS calcd for C H NO : 326.1756. Found:
(
JMOD, 75 MHz, CDCl
3
(
(
3
2
2
3
3
3
+
+
4
+
+
3
4
20 24
−
1
26.1751. IR (cm ): 3034, 2980, 1719, 1680, 1407, 1243, 1157, 715.
1
0
De Martino, G.; Scalzo, M.; Massa, S.; Giuliano, R. Farmaco, Edizione Scientifica, 1973, 28, 976
S-11

(
±)-trans-5-Allyl-1-benzyl-4-isopropyl-4,5-dihydrocyclopenta[b]pyrrol-6(1H)-one (24)
Lithium diisopropylamide (0.5 M in THF / cyclohexane, 0.59 mL, 0.30 mmol) was added slowly to a stirred solution of 23
57.8 mg, 0.228 mmol) in tetrahydrofuran (2 mL) at −78 °C and the solution was then allowed to warm to room temperature.
(
This solution was then re-cooled to −78 °C and allyl bromide (150 μL, 1.72 mmol) was added. The solution was then allowed
to come to room temperature and was stirred for 4 hours. After this time the reaction was taken up in diethyl ether (20 mL)
and distilled water (40 mL). The organic phase was separated and the aqueous phase was re-extracted with diethyl ether (2 ×
1
(
0 mL). The combined organic extracts were dried over MgSO
silica gel, 91:9 hexane / diethyl ether) gave the title compound as a viscous oil (55.0 mg, 82%). H NMR (300 MHz, CDCl
, 1H), 5.33-5.21 (m, 2H), 5.09 (dd, J = 17.1,
.6 Hz, 1H), 5.00 (dd, J = 9.9, 1.6 Hz, 1H), 2.75 (dd, J = 5.6, 2.0 Hz, 1H), 2.67-2.52 (m, 2H), 2.43 (dt, J = 13.8, 7.5 Hz, 1H),
4
and concentrated onto silica (1 g). Flash chromatography
1
3
)

1
1

1
6
7.35-7.20 (m, 5H), 6.98 (d, J = 1.8 Hz, 1H), 6.05 (d, J = 1.8 Hz, 1H), 5.77 (m
c
13
.87 (app. octet, Japp = 6.5 Hz, 1H), 0.99 (d, J = 6.6 Hz, 3H), 0.88 (d, J = 6.6 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl
192.7 (C), 153.0 (C), 138.6 (CH), 137.3 (C), 135.7 (CH), 133.8 (CH), 133.4 (C), 128.7 (CH), 127.8 (CH), 127.6 (CH),
16.8 (CH ), 106.3 (CH), 56.6 (CH), 50.7 (CH ), 45.7 (CH), 36.5 (CH ), 31.6 (CH), 20.8 (CH ), 19.1 (CH ). LRMS m/z (%):
04.6 (10, 2×M+NH 24NO : 294.1858. Found: 294.1856.
3
)
2
2
2
3
3
+
+
+
+
4
), 587.5 (25, 2×M+H ), 294.2.2 (100, MH ). HRMS calcd for C20H
−1
IR (cm ): 3068, 2958, 1672, 1509, 1412, 1067, 913, 722.
3
,4-Dihydro-2H-pyran-6-carbonyl chloride (15j)
t-Butyllithium (1.70 M in pentane, 15.0 mL, 25.5 mmol) was added dropwise to a stirred solution of dihydropyran (21) (2.90
mL, 30.6 mmol) in tetrahydrofuran (40 mL) at –78 °C. After addition was complete the resultant solution was allowed to
warm to room temperature before being cooled again to –78 °C. The nitrogen was turned off and carbon dioxide was bubbled
slowly through the solution while it was warmed to 0ºC (ice bath) over the course of 30 minutes. The carbon dioxide supply
was then removed and the reaction mixture was partitioned between diethyl ether (60 mL) and distilled water (60 mL). The
aqueous phase was collected and the organic phase was re-extracted with distilled water (60 mL). The combined aqueous
extracts were acidified to pH 2 with 2 M hydrochloric acid. This mixture was extracted with ethyl acetate (4 × 30 mL) and the
organic extracts were dried over magnesium sulphate and concentrated under reduced pressure to give 1.74 g of crude acid 22
that was used without further purification.
Crude acid 22 was dissolved in dry dichloromethane (25 mL) and to it was added thionyl chloride (7.0 mL, 95 mmol). After
stirring for 24 hours the reaction mixture concentrated under reduced pressure to give the title compound 15j as a tan oil (1.34
1
g, 36%). H NMR (300 MHz, CDCl
3
) 6.43 (t, J = 4.4 Hz, 1H), 4.10 (t, J = 5.1 Hz, 2H), 2.27 (td, J = 6.4, 4.4 Hz, 2H), 1.85
)  163.6 (C), 146.7 (C), 119.4 (CH), 67.1 (CH ), 21.4 (CH ),
). IR (cm ): 2939, 1755, 1626, 1168, 1055, 934, 746.
1
3
(
tt, J = 6.4, 5.1 Hz, 2H). C NMR (JMOD, 75 MHz, CDCl
3
2
2
−
1
2
0.8 (CH
2
General Procedure B: Preparation of N-Alkynoyloxazolidinones 29.
n-Butyllithium (1.82 M in cyclohexane, 5.5 mL, 10.0 mmol) was added dropwise to a stirred solution of alkyne 26 (12.0
mmol) in tetrahydrofuran (30 mL) at −78 °C under nitrogen. After stirring for 30 minutes the nitrogen was turned off and
carbon dioxide was bubbled slowly through the solution while it was warmed to 0°C (ice bath) over the course of 30 minutes.
The carbon dioxide supply was then removed and replaced with the nitrogen atmosphere. The solution was again cooled to
−78 °C and pivaloyl chloride (1.24 mL, 10.0 mmol) was added. The solution was then allowed to warm to room temperature
and was stirred for 3 hours. The solution was then cooled again to −78 °C and to it was added via cannula a solution of
lithiated oxazolidinone (10.0 mmol, generated by addition of 5.5 mL of 1.82 M butyllithium solution to 1.63 g of
oxazolidinone 28 in 60 mL of tetrahydrofuran) at −78 °C. The solution was then allowed to warm to room temperature and
stirred for 2 hours. After this time the solution was concentrated to a volume of 20 mL under vacuum. Ethyl acetate (50 mL)
and distilled water (50 mL) were then added and the organic phase was separated, the aqueous phase was re-extracted with
S-12

ethyl acetate (30 mL) and the combined organic extracts were dried over magnesium sulphate and concentrated onto silica gel
(
5 g) under reduced pressure. The solid residue was subjected to flash chromatography.
(S)-3-Hex-2-ynoyl-4-phenyloxazolidin-2-one (29a)
This material was prepared from alkyne 26a and oxazolidinone 28a in accordance with General Procedure B. After flash
chromatography (silica gel, 5:5:1 hexane / dichloromethane / diethyl ether) the title compound was obtained as a viscous oil
1
(
(
(
(
65%). H NMR (300 MHz, CDCl
3
) 7.42-7.27 (m, 5H), 5.43 (dd, J = 8.7, 3.6 Hz, 1H), 4.68 (app. t, Japp = 8.7 Hz, 1H), 4.28
1
3
dd, J = 8.7, 3.6 Hz, 1H), 2.41 (t, J = 7.1 Hz, 2H), 1.65 (app. sext, Japp = 7.2 Hz, 2H), 1.04 (t, J = 7.4 Hz, 3H). C NMR
JMOD, 75 MHz, CDCl
CH
3
) 152.2 (C), 150.1 (C), 138.6 (C), 129.0 (CH), 128.5 (CH), 125.8 (CH), 98.3 (C), 73.8 (C), 69.8
+
+
2
), 57.4 (CH), 21.0 (CH
2
+
), 20.8 (CH
2
), 13.3 (CH
3 4
). LRMS m/z (%): 537.4 (20), 275.2 (70, M+NH ), 258.2 (100, MH ).
−1
HRMS calcd for C15
H
16NO : 258.1130. Found: 258.1128. IR (cm ): 2967, 2238, 2221, 1788, 1662, 1322, 1195, 1088, 1039.
3
(S)-4-tert-Butyl-3-hex-2-ynoyloxazolidin-2-one (29b)
This material was prepared from alkyne 26a and oxazolidinone 28b in accordance with General Procedure B. After flash
chromatography (silica gel, 5:5:1 hexane / dichloromethane / diethyl ether) the title compound was obtained as a viscous oil
1
(
1
43%). H NMR (300 MHz, CDCl
3
) 4.40 (dd, J = 7.4, 1.7 Hz, 1H), 4.29 (dd, J = 9.2, 1.7 Hz, 1H), 4.23 (dd, J = 9.2, 7.4 Hz,
1
3
H), 2.43 (t, J = 7.1 Hz, 2H), 1.67 (app. sext, Japp = 7.2 Hz, 2H), 1.06 (t, J = 7.4 Hz, 3H), 0.96 (s, 9H). C NMR (JMOD, 75
MHz, CDCl ) 153.0 (C), 151.0 (C), 98.5 (C), 73.4 (C), 65.1 (CH ), 61.2 (CH), 35.7 (C), 25.4 (CH ), 21.1 (CH ), 20.9
CH ), 13.3 (CH : 260.1263.
Found: 260.1252. IR (cm ): 2965, 2241, 2219, 1790, 1666, 1324, 1295, 1183, 1090.
3
2
3
2
+
+
+
(
2
3 4 3
). LRMS m/z (%): 255.3 (65, M+NH ), 238.2 (100, MH ). HRMS calcd for C13H19NNaO
−1
(4S,5R)-3-Hex-2-ynoyl-4,5-diphenyloxazolidin-2-one (29c)
This material was prepared from alkyne 26a and oxazolidinone 28c in accordance with General Procedure B. After flash
chromatography (silica gel, 5:5:1 hexane / dichloromethane / diethyl ether) the title compound was obtained as a white solid
1
(
43%). Mp = 131-133 °C. H NMR (300 MHz, CDCl
3
) 7.16-7.07 (m, 6H), 7.01-6.94 (m, 2H), 6.91-6.84 (m, 2H), 5.89 (d, J
=
7.5 Hz, 1H), 5.67 (d, J = 7.5 Hz, 1H), 2.44 (t, J = 7.1 Hz, 2H), 1.68 (app. sext, Japp = 7.3 Hz, 2H), 1.06 (t, J = 7.4 Hz, 3H).
1
3
C NMR (JMOD, 75 MHz, CDCl
3
) 152.2 (C), 150.0 (C), 133.9 (C), 132.7 (C), 128.4 (CH), 128.23 (CH), 128.18 (CH),
), 20.9 (CH ), 13.4 (CH ). LRMS
), 334.2 (100, MH ). HRMS calcd for C21 : 356.1263. Found:
1
28.0 (CH), 126.6 (CH), 126.1 (CH), 98.8 (C), 80.1 (CH), 73.8 (C), 62.7 (CH), 21.2 (CH
2
2
3
+
+
+
+
m/z (%): 684.5 (50, 2×M+NH
4
), 351.3 (60, M+NH
4
H19NNaO
3
−
1
3
56.1257. IR (cm ): 3035, 2966, 2262, 2214, 1771, 1663, 1362, 1341, 1315, 1192, 1022, 729.
S-13

(3aS,8aR)-3-Hex-2-ynoyl-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazol-2-one (29d)
This material was prepared from alkyne 26a and oxazolidinone 28d in accordance with General Procedure B. After flash
chromatography (silica gel, 5:5:1 hexane / dichloromethane / diethyl ether) the title compound was obtained as a viscous oil
1
(
43%). H NMR (300 MHz, CDCl
3
) 7.66 (d, J = 7.8 Hz, 1H), 7.39-7.23 (m, 3H), 5.93 (d, J = 6.9 Hz, 1H), 5.28 (ddd, J =
6
7
.9, 4.2, 3.0 Hz, 1H), 3.40 (app. d, J = 3.0 Hz, 2H), 2.43 (t, J = 7.1 Hz, 2H), 1.66 (app. sext, Japp = 7.3 Hz, 2H), 1.05 (t, J =
app
13
.4 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl ) 151.4 (C), 151.1 (C), 139.3 (C), 138.5 (C), 129.9 (CH), 128.1 (CH), 127.2
3
(
5
2
CH), 125.1 (CH), 99.2 (C), 77.9 (CH), 73.5 (C), 62.9 (CH), 37.9 (CH ), 21.2 (CH ), 20.9 (CH ), 13.3 (CH ). LRMS m/z (%):
2
2
2
3
+
+
+
+
56.4 (10, 2×M+NH
4
), 287.3 (70, M+NH
4
), 270.2 (100, MH ). HRMS calcd for C16
H
15NNaO
3
: 292.0950. Found:
−
1
92.0944. IR (cm ): 2966, 2250, 2224, 1787, 1656, 1360, 1324, 1189, 1101, 1032, 753.
(S)-4-Phenyl-3-(3-phenylpropioloyl)oxazolidin-2-one (29e)
This material was prepared from alkyne 26b and oxazolidinone 28a in accordance with General Procedure B. After flash
1
chromatography (silica gel, 4:1 hexane / ethyl acetate) the title compound was obtained as a white solid (41%). H NMR (300
MHz, CDCl
3
) 7.66 (d, J = 7.2 Hz, 2H), 7.49-7.30 (m, 8H), 5.50 (dd, J = 8.7, 3.6 Hz, 1H), 4.73 (app. t, Japp = 8.7 Hz, 1H),
1
1
4
.33 (dd, J = 8.7, 3.6 Hz, 1H). Known compound.
(S)-4-Isopropyl-3-(3-phenylpropioloyl)oxazolidin-2-one (29f)
This material was prepared from alkyne 26b and oxazolidinone 28e in accordance with General Procedure B. After flash
chromatography (silica gel, 83:17 hexanes / ethyl acetate) the title compound was obtained as a white solid (48%). Mp = 91-
1
9
3 °C. H NMR (300 MHz, CDCl
3
)  7.67 (d, J = 7.2 Hz, 2H), 7.49-7.33 (m, 3H), 4.48 (ddd, J = 8.1, 4.2, 3.0 Hz, 1H), 4.30
(
app. t, Japp = 8.6 Hz, 1H), 4.23 (dd, J = 9.0, 3.0 Hz, 1H), 2.44 (sept.d, J = 6.9, 4.2 Hz, 1H), 0.95 (d, J = 6.9 Hz, 3H), 0.92 (d, J
13
=
9
3
6.9 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl ) 152.6 (C), 150.9 (C), 133.3 (CH), 131.0 (CH), 128.6 (CH), 119.9 (C),
+
4.5 (C), 81.3 (C), 63.4 (CH ), 58.7 (CH), 28.6 (CH), 18.0 (CH ), 14.8 (CH ). LRMS m/z (%): 275.2 (45, M+NH ), 258.2
2 3 3 4
+
+
−1
(100, MH ). HRMS calcd for C15
H16NO
3
: 258.1130. Found: 258.1124. IR (cm ): 2961, 2214, 1778, 1658, 1365, 1322,
1
200, 762.
O
O
O
O
O
N
O
O
Ph
N
Cl
Ph
O
(2Z,4E)-2-Butylidene-4-methyl-1-[(S)-2-oxo-4-phenyloxazolidin-3-yl]hex-4-ene-1,3-dione (30a)
Alkyne 29a was reacted with acid chloride 15g in accordance with General Procedure A giving the product 30a after flash
chromatography (silica gel, 10:10:1, hexane / dichloromethane / diethyl ether) as a white crystalline solid (99%). Mp = 104-
1
1
4
05 °C. H NMR (300 MHz, CDCl
3
) 7.50-7.30 (m, 5H), 6.62 (t, J = 7.7 Hz, 1H), 6.52 (q, J = 6.6 Hz, 1H), 5.52 (dd, J = 8.9,
.1 Hz, 1H), 4.73 (app. t, Japp = 8.9 Hz, 1H), 4.27 (dd, J = 8.7, 4.1 Hz, 1H), 2.13 (app. q, Japp = 7.4 Hz, 2H), 1.86 (s, 3H), 1.82
1
1
Fonquerna, S.; Moyano, A.; Pericas, M.A.; Riera, A. Tetrahedron: Asymmetry, 1997, 8, 1685.
S-14

1
3
(
(
7
3
2
d, J = 6.6 Hz, 3H), 1.47 (app. sext, Japp = 7.4 Hz, 2H), 0.89 (t, J = 7.2 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl
3
)  194.8
C), 165.7 (C), 153.1 (C), 148.7 (CH), 138.6 (C), 137.5 (CH), 137.3 (C), 135.5 (C), 129.0 (CH), 128.5 (CH), 126.0 (CH),
+
0.4 (CH
59.3 (20, M+NH
2
), 57.4 (CH), 31.7 (CH
2
), 21.7 (CH
2
), 14.3 (CH
3 3 3 4
), 13.7 (CH ), 12.6 (CH ). LRMS m/z (%): 700.4 (20, 2×M+NH ),
+
+
+
−1
4
), 342.2 (100, MH ), 179 (15). HRMS calcd for C20H24NO : 342.1705. Found: 342.1704. IR (cm ):
4
924, 1779, 1718, 1693, 1489, 1332, 1279, 1197, 1023, 699.
O
O
O
O
O
N
O
O
N
Cl
O
(2Z,4E)-1-[(S)-4-tert-Butyl-2-oxo-oxazolidin-3-yl]-2-butylidene-4-methylhex-4-ene-1,3-dione (30b)
Alkyne 29b was reacted with acid chloride 15g in accordance with General Procedure A giving the product 30b after flash
1
chromatography (silica gel, 22:3 hexane / ethyl acetate) as a thick oil (81%). H NMR (300 MHz, CDCl
3
) 6.60 (t, J = 7.8
Hz, 1H), 6.55 (m
c
, 1H) 4.48 (dd, J = 6.3, 3.0 Hz, 1H), 4.33-4.26 (m, 2H), 2.31-2.19 (m, 2H), 1.88-1.82 (m, 6H), 1.54 (app.
1
3
sext, Japp = 7.3 Hz, 2H), 1.02 (s, 9H), 0.96 (t, J = 7.4 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl )  195.2 (C), 166.3 (C),
3
1
(
54.1 (C), 147.9 (CH), 137.8 (C), 137.5 (CH), 135.2 (C), 65.6 (CH
CH ), 14.2 (CH ), 13.7 (CH ), 12.5 (CH ). LRMS m/z (%): 660.7 (20, 2×M+NH
HRMS calcd for C18
2 2 3
), 61.1 (CH), 35.9 (C), 32.0 (CH ), 25.5 (CH ), 21.7
+
+
+
2
3
3
3
4
), 339.3 (25, M+NH
4
27NNaO : 344.1838. Found: 344.1830. IR (cm ): 2964, 1780, 1699, 1370, 1190, 1114.
4
), 322.2 (100, MH ).
+
−1
H
(2Z,4E)-2-Butylidene-4-methyl-1-[(4S,5R)-2-oxo-4,5-diphenyloxazolidin-3-yl]hex-4-ene-1,3-dione (30c)
Alkyne 29c was reacted with acid chloride 15g in accordance with General Procedure A giving the product 30c after flash
1
3
chromatography (silica gel, 87:13 hexane / ethyl acetate) as a tan solid (86%). Mp = 52-54 °C. H NMR (300 MHz, CDCl )
7.15-7.07 (m, 6H), 6.99-6.92 (m, 4H), 6.68 (t, J = 7.8 Hz, 1H), 6.59 (q, J = 6.9, Hz, 1H), 5.95 (d, J = 7.7 Hz, 1H), 5.77 (d, J
=
7.7 Hz, 1H), 2.19 (app. q, Japp = 7.6 Hz, 2H), 1.91 (s, 3H), 1.87 (d, J = 6.9 Hz, 3H), 1.52 (app. sext, Japp = 7.4 Hz, 2H), 0.93
1
3
(
t, J = 7.4 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl
3
)  195.0 (C), 165.6 (C), 153.1 (C), 148.8 (CH), 137.7 (CH), 137.6 (C),
1
35.5 (C), 134.2 (C), 132.9 (C), 128.3 (CH), 128.1 (CH), 128.0 (CH), 127.9 (CH), 126.8 (CH), 126.2 (CH), 80.7 (CH), 62.5
+
(CH), 31.9 (CH
2
), 21.8 (CH
), 418.5 (100, MH ). HRMS calcd for C26
2
), 14.3 (CH
3
), 13.8 (CH
3
), 12.7 (CH
3
). LRMS m/z (%): 852.3 (15, 2×M+NH
4
), 435.3 (40,
+
+
+
−1
M+NH
4
H
27NNaO
4
: 440.1838. Found: 440.1830. IR (cm ): 3036, 2961, 1782,
1
694, 1633, 1343, 1187, 697.
(2Z,4E)-2-Butylidene-4-methyl-1-[(3aS,8aR)-2-oxo-2H-indeno[1,2-d]oxazol-3(3aH,8H,8aH)-yl]hex-4-ene-1,3-dione
(30d)
Alkyne 29d was reacted with acid chloride 15g in accordance with General Procedure A giving the product 30b after flash
1
chromatography (silica gel, 21:4 hexane / ethyl acetate) as a thick oil (86%). H NMR (300 MHz, CDCl
3
) 7.77 (d, J = 7.2
, 1H), 3.47-
Hz, 1H), 7.39-7.26 (m, 3H), 6.64, (t, J = 7.8 Hz, 1H), 6.50 (q, J = 6.8 Hz, 1H), 6.03 (d, J = 6.9 Hz, 1H), 5.32 (m
.31 (m, 2H), 2.29-2.19 (m, 2H), 1.82 (s, 3H), 1.78 (d, J = 6.8 Hz, 3H), 1.58-1.43 (m, 2H), 0.91 (t, J = 7.4 Hz, 3H). C NMR
JMOD, 75 MHz, CDCl )  194.6 (C), 166.8 (C), 152.4 (C), 148.4 (CH), 139.5 (C), 139.0 (C), 137.8 (CH), 137.5 (C), 135.6
C), 129.9 (CH), 128.2 (CH), 127.3 (CH), 125.3 (CH), 78.8 (CH), 63.0 (CH), 38.0 (CH ), 32.0 (CH ), 21.8 (CH ), 14.4 (CH ),
), 354.2 (100, MH ). HRMS calcd for
c
13
3
(
3
(
1
2
+
2
2
3
+
+
3 3 4 4
3.9 (CH ), 12.6 (CH ). LRMS m/z (%): 724.5 (30, 2×M+NH ), 371.3 (15, M+NH
+
−1
C H NNaO : 376.1525. Found: 376.1518. IR (cm ): 2962, 1778, 1687, 1633, 1362, 1282, 1191, 1040, 756.
2
1
23
4
S-15

(S,Z)-2-Butylidene-1-(3,4-dihydro-2H-pyran-6-yl)-3-(2-oxo-4-phenyloxazolidin-3-yl)propane-1,3-dione (30e)
Alkyne 29a was reacted with acid chloride 15j in accordance with General Procedure A giving the product 30e after flash
1
chromatography (silica gel, 7:3 hexanes / ethyl acetate) as a tan oil (70%). H NMR (300 MHz, CDCl
3
) 7.48-7.30 (m, 5H),
7
9
.00 (t, J = 8.0 Hz, 1H), 5.96 (t, J = 4.1 Hz, 1H), 5.51 (dd, J = 8.7, 4.2 Hz, 1H), 4.72 (app. t, Japp = 8.7 Hz, 1H), 4.31 (dd, J =
.0, 4.2 Hz, 1H), 4.00-3.90 (m, 2H), 2.24-2.06 (m, 4H), 1.88−1.80 (m, 2H), 1.47 (app. sext, Japp = 7.4 Hz, 2H), 0.88 (t, J = 7.4
1
3
Hz, 3H). C NMR (JMOD, 75 MHz, CDCl
1
2
3
)  184.7 (C), 165.2 (C), 153.1 (C), 150.3 (C), 149.4 (CH), 138.7 (C), 135.7 (C),
28.9 (CH), 128.5 (CH), 126.2 (CH), 111.8 (CH), 70.3 (CH ), 66.1 (CH ), 57.2 (CH), 31.6 (CH ), 21.6 (CH ), 21.4 (CH ),
), 370.3 (100, MH ), 164.0 (80). HRMS
2
2
2
2
2
+
+
+
2 3 4 4
0.5 (CH ), 13.7 (CH ). LRMS m/z (%): 756.4 (10, 2×M+ NH ), 387.4 (60, M+NH
+
−1
calcd for C21
H
24NNaO
5
: 392.1474. Found: 392.1473. IR (cm ): 2962, 1777, 1696, 1385, 1325, 1202, 1038, 733, 700.
O
O
O
O
O
N
O
O
Ph
N
MeO
Cl
Ph
MeO
O
(S,Z)-2-Butylidene-1-(3-methoxyphenyl)-3-(2-oxo-4-phenyloxazolidin-3-yl)propane-1,3-dione (30f)
Alkyne 29a was reacted with acid chloride 15k in accordance with General Procedure A giving the product 30f after flash
1
chromatography (silica gel, 25:25:2 hexane / dichloromethane / diethyl ether as a thick tan oil (91%). H NMR (300 MHz,
CDCl
3
c
) 7.45-7.30 (m, 8H), 7.08 (m , 1H), 6.65 (t, J = 7.8 Hz, 1H), 5.57 (dd, J = 8.9, 4.4 Hz, 1H), 4.75 (app. t, Japp = 8.9 Hz,
1
H), 4.28 (dd, J = 8.9, 4.4 Hz, 1H), 3.83 (s, 3H), 2.20 (app. q, J = 7.5 Hz, 2H), 1.47 (app. sext, Japp = 7.4 Hz, 2H), 0.90 (t, J
app
1
3
=
7.4 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl
3
)  193.4 (C), 165.2 (C), 159.4 (C), 153.4 (C), 150.6 (CH), 138.7 (C), 138.3
(
(
(
2
C), 137.9 (C), 129.2 (CH), 129.0 (CH), 128.5 (CH), 126.0 (CH), 122.1 (CH), 118.3 (CH), 114.2 (CH), 70.6 (CH ), 57.3
+
+
CH), 55.2 (CH
3
), 31.8 (CH
100, MH ). HRMS calcd for C23
285, 1204, 1041, 733, 700.
2
), 21.7 (CH
2
), 13.7 (CH
3
). LRMS m/z (%): 804.5 (20, 2×M+NH
4
), 411.4 (40, M+NH
4
), 394.4
+
+
−1
H24NO
5
: 394.1654. Found: 394.1661. IR (cm ): 3034, 2962, 1779, 1696, 1649, 1375,
1
(2Z,4E)-2-Benzylidene-4-methyl-1-[(S)-2-oxo-4-phenyloxazolidin-3-yl]hex-4-ene-1,3-dione (30g)
Alkyne 29e was reacted with acid chloride 15g in accordance with General Procedure A giving the product 30g after flash
1
chromatography (silica gel, 5:5:1 hexanes / dichloromethane / diethyl ether) as a white solid (88%). Mp = 116-117 °C. H
NMR (300 MHz, CDCl
3
c
)  7.41 (br. s, 5H), 7.35 (s, 1H), 7.27 (m , 1H), 7.12 (br. s, 4H), 6.65 (q, J = 6.6 Hz, 1H), 5.55 (dd, J
=
8.4 Hz, J = 3.3 Hz, 1H), 4.71 (t, J = 8.4 Hz, 1H), 4.33 (dd, J = 8.4 Hz, J = 3.3 Hz, 1H), 1.91 (s, 3H), 1.75 (d, J = 6.6 Hz,
1
3
3
1
H). C NMR (JMOD, 75 MHz, CDCl
35.0 (C), 133.0 (C), 130.0 (CH),129.3 (CH), 129.0 (CH), 128.7 (CH), 128.6 (CH), 126.6 (CH), 70.4 (CH
3
)  195.4 (C), 166.2 (C), 152.8 (C), 143.0 (CH), 138.4 (CH), 138.1 (C), 135.4 (C),
), 57.4 (CH), 14.5
3
). IR (KBr disc, cm ): 3043, 2913, 1783, 1699, 1637, 1622, 1393, 1368, 1333, 1282, 1262, 1222, 1120,
2
−1
(
CH
3
), 12.8 (CH


+
1
064. LRMS (70 eV) m/z (%): 375 ( 20), 292 (25), 212 (100). HRMS (FAB) calcd for C23H22NO (M+H ): 376.1549.
4
Found: 376.1552. A NOSEY 2D NMR experiment was performed and is provided in the Supplementary Information.
S-16

(S,Z)-2-Benzylidene-1-(3,4-dihydro-2H-pyran-6-yl)-3-(2-oxo-4-phenyloxazolidin-3-yl)propane-1,3-dione (30h)
Alkyne 29e was reacted with acid chloride 15j in accordance with General Procedure A giving the product 30j after flash
1
chromatography (silica gel, 13:7 hexanes / ethyl acetate) as a white solid (69%). Mp = 70-72 °C. H NMR (300 MHz, CDCl )
3

4
1
1
7.79 (s, 1H), 7.43-7.10 (m, 10H), 6.04 (t, J = 4.1 Hz, 1H), 5.50 (dd, J = 8.6, 3.5 Hz, 1H), 4.62 (app. t, Japp = 8.7 Hz, 1H),
1
3
.33 (dd, J = 9.0, 3.5 Hz, 1H), 3.97 (br. s, 2H), 2.27-2.19 (m, 2H), 1.92-1.81 (m, 2H). C NMR (JMOD, 75 MHz, CDCl
84.9 (C), 166.0 (C), 152.8 (C), 150.5 (C), 143.5 (CH), 138.2 (C), 133.3 (C), 133.2 (C), 130.1 (CH), 129.5 (CH), 129.0 (CH),
28.64 (CH), 128.55 (CH), 126.8 (CH), 112.4 (CH), 70.3 (CH ), 66.2 (CH ), 57.4 (CH), 21.5 (CH ), 20.6 (CH ). LRMS m/z
), 404.2 (100, MH ). HRMS calcd for C24 : 426.1317. Found:
26.1316. IR (cm ): 2926, 1779, 1692, 1619, 1260, 1200, 756, 696.
3
) 
2
2
2
2
+
+
+
+
(%): 824.4 (10, 2×M+NH
4
), 421.2 (35, M+NH
4
H21NNaO
5
−
1
4
(S,Z)-2-Benzylidene-1-(3-methoxyphenyl)-3-(2-oxo-4-phenyloxazolidin-3-yl)propane-1,3-dione (30i)
Alkyne 29e was reacted with acid chloride 15k in accordance with General Procedure A giving the product 30i after flash
1
chromatography (silica gel, 10:10:1 hexane / dichloromethane / diethyl ether) as a white solid (79%). Mp = 146-148 °C. H
NMR (300 MHz, CDCl
3
) 7.50-7.35 (m, 9H), 7.29 (m
c
, 1H), 7.22-7.00 (m, 5H), 5.62 (dd, J = 8.7, 3.5 Hz, 1H), 4.76 (app. t,
13
J
1
app = 8.7 Hz, 1H), 4.37 (dd, J = 8.7, 3.5 Hz, 1H), 3.85 (s, 3H). C NMR (JMOD, 75 MHz, CDCl
3
)  194.1 (C), 165.8 (C),
59.5 (C), 153.1 (C), 144.8 (CH), 138.4 (C), 138.2 (C), 135.4 (C), 132.7 (C), 130.5 (CH), 129.6 (CH), 129.4 (CH), 129.1
), 57.4 (CH), 55.4 (CH ). LRMS m/z (%):
(
CH), 128.7 (CH), 126.7 (CH), 122.2 (CH), 118.5 (CH), 114.2 (CH), 70.6 (CH
2
3
+
+
+
+
8
4
72.4 (30, 2×M+NH
4
), 445.3 (55, M+NH
4 5
), 428.3 (100, MH ). HRMS calcd for C26H21NNaO : 450.1317. Found:
−
1
50.1316. IR (cm ): 2927, 1777, 1695, 1649, 1577, 1319, 1288, 1215, 1047, 692.
(S,Z)-1-(1-Benzyl-1H-pyrrol-2-yl)-2-benzylidene-3-(2-oxo-4-phenyloxazolidin-3-yl)propane-1,3-dione (30j)
Alkyne 29e was reacted with acid chloride 15i in accordance with General Procedure A giving the product 38 after flash
1
3
chromatography (silica gel, 7:3 hexanes / ethyl acetate) as a yellow solid (72%). Mp = 77-81 °C. H NMR (300 MHz, CDCl )

1
1
c
7.54 (s, 1H), 7.45-7.00 (m, 16H), 6.95 (s, 1H), 6.21 (s, 1H), 5.62-5.42 (m, 3H), 4.67 (app. t, Japp = 8.6 Hz, 1H), 5.30 (m ,
1
3
H). C NMR (75 MHz, CDCl
3
)  181.9 (C), 165.8 (C), 152.4 (C), 141.8 (CH), 137.9 (C), 137.8 (C), 136.2 (C), 132.8 (C),
30.4 (CH), 129.6 (CH), 129.0 (CH), 128.6 (CH), 128.2 (CH, 3 overlapping resonances), 127.1 (CH), 127.0 (CH), 126.4
+
2 2 25 2 4
(CH), 122.1 (CH), 108.6 (CH), 70.0 (CH ), 57.0 (CH), 51.5 (CH ). HRMS calcd for C30H N O : 477.1809. Found:
4
77.1827.
(2Z,4E)-2-Benzylidene-1-[(S)-4-isopropyl-2-oxooxazolidin-3-yl]-4-methylhex-4-ene-1,3-dione (30k)
Alkyne 29f was reacted with acid chloride 15g in accordance with General Procedure A giving the product 30j after flash
1
chromatography (silica gel, 83:17 hexanes / ethyl acetate) as a white solid (92%). Mp = 117-119 °C. H NMR (300 MHz,
S-17

CDCl
3
) 7.41-7.32 (m, 6H), 6.67 (q, J = 6.8 Hz, 1H), 4.53 (ddd, J = 8.1, 3.8, 3.3 Hz, 1H), 4.28 (app. t, Japp = 8.6 Hz, 1H),
4
3
1
.21 (dd, J = 9.0, 3.3 Hz, 1H), 2.51 (sept.d, J = 6.8, 3.8 Hz, 1H), 1.91 (s, 3H), 1.89 (d, J = 6.8 Hz, 3H), 0.95 (d, J = 6.8 Hz,
13
H), 0.91 (d, J = 6.8 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl
36.0 (C), 135.5 (C), 133.6 (C), 130.1 (CH), 129.2 (CH), 128.8 (CH), 63.9 (CH
3
) 195.3 (C), 166.8 (C), 153.4 (C), 142.5 (CH), 138.3 (CH),
), 58.5 (CH), 28.5 (CH), 17.8 (CH ), 14.7
), 342.4 (100, MH ). HRMS
2
3
+
4
+
+
(
CH
calcd for C20
94.
3
), 14.4 (CH
3
), 12.8 (CH
3
). LRMS m/z (%): 700.6 (20, 2×M+NH
), 359.4 (15, M+NH
4
+
−1
H
23NNaO
4
: 364.1525. Found: 364.1520. IR (cm ): 2964, 1776, 1687, 1612, 1381, 1282, 1209, 1146, 1109, 763,
6
O
O
O
O
O
O
N
N
O
O
(S)-4-tert-Butyl-3-[(1S,5S)-3,4-dimethyl-2-oxo-5-propylcyclopent-3-enecarbonyl]oxazolidin-2-one (31bC)
Conditions A: The reaction was performed as described for 31aC using 30b giving 31bA and 31bC after flash
1
chromatography (silica gel, 50:50:6 hexane / dichloromethane / diethyl ether). Major isomer 31bC clear oil (74%). H NMR
(
1
(
(
300 MHz, CDCl
.42-1.29 (m, 3H), 0.96 (s, 9H), 0.96 (t, J = 6.6 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl
C), 155.1 (C), 133.7 (C), 65.2 (CH ), 62.3 (CH), 55.7 (CH), 46.4 (CH), 35.5 (C), 34.0 (CH
CH ), 13.9 (CH ), 8.1 (CH ). LRMS m/z (%): 660.5 (30, 2×M+NH
3
) δ 4.87 (d, J = 3.0 Hz, 1H), 4.37-4.29 (m, 3H), 3.29 (m
c
, 1H), 2.05 (s, 3H), 1.85 (m
) δ 201.4 (C), 173.3 (C), 169.1
), 25.7 (CH ), 20.6 (CH ), 15.0
), 322.3 (100, MH ). HRMS calcd
: 344.1838. Found: 344.1828. IR (cm ): 2962, 1778, 1690, 1643, 1365, 1182, 1053, 706. Minor isomer
c
, 1H), 1.67 (s, 3H),
1
3
3
2
2
3
2
+
+
+
3
3
3
4 4
), 339.3 (15, M+NH
+
−1
for C18
H
27NNaO
4
1
3
1
1
5
6
3
1bA clear oil (19%). H NMR (300 MHz, CDCl ) δ 4.98 (br s, 1H), 4.52 (dd, J = 7.7, 1.9 Hz, 1H), 4.33 (dd, J = 9.3, 1.9 Hz,
3
H), 4.27 (dd, J = 9.3, 7.7 Hz, 1H), 3.28 (m
c
, 1H), 2.04 (s, 3H), 1.77 (m
) δ 200.7 (C), 172.7 (C), 169.5 (C), 154.3 (C), 133.9 (C), 65.0 (CH
6.4 (CH), 45.9 (CH), 36.2 (C), 33.9 (CH ), 25.4 (CH ), 20.4 (CH ), 15.0 (CH ), 14.0 (CH ), 8.2 (CH ). LRMS m/z (%):
), 322.3 (100, MH ). HRMS calcd for C18
c
, 1H), 1.69 (s, 3H), 1.36-1.23 (m, 3H), 0.99-0.90 (m,
1
3
2H). C NMR (JMOD, 75 MHz, CDCl
3
2
), 61.2 (CH),
2
3
2
3
3
3
+
+
+
+
60.5 (20, 2×M+NH
4
), 339.2 (10, M+NH
4
4
H27NNaO : 344.1838. Found:
−
1
44.1832. IR (cm ): 2961, 1775, 1690, 1646, 1323, 1184, 1056, 706.
Ph
Ph
Ph
O
O
O
O
N
Ph
O
O
N
O
O
(4S,5R)-3-[(1S,5S)-3,4-Dimethyl-2-oxo-5-propylcyclopent-3-enecarbonyl]-4,5-diphenyloxazolidin-2-one (31cC)
Conditions A: The reaction was performed as described for 31aC using 30c giving 31cA and 31cC after flash
chromatography (silica gel, 50:50:4 hexane / dichloromethane / diethyl ether). Major isomer 31cC white solid (71%). Mp =
1
1
1
3
1
43-145 °C. H NMR (300 MHz, CDCl
3
) δ 7.17-7.07 (m, 6H), 7.02-6.96 (m, 2H), 6.89-6.84 (m, 2H), 6.02 (d, J = 7.4 Hz,
, 1H), 2.03 (s, 3H), 1.80 (m , 1H), 1.71 (s, 3H), 1.43-1.25 (m,
H), 0.90 (t, J = 6.8 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl ) δ 201.0 (C), 173.4 (C), 168.3 (C), 154.0 (C), 134.5 (C),
33.8 (C), 132.6 (C), 128.3 (CH), 128.2 (CH), 128.0 (CH), 127.9 (CH), 126.4 (CH), 126.1 (CH), 80.3 (CH), 63.5 (CH), 56.3
H), 5.63 (d, J = 7.4 Hz, 1H), 5.00 (d, J = 3.0 Hz, 1H), 3.20 (m
c
c
13
3
+
(
(
CH), 46.1 (CH), 33.9 (CH
2
), 20.5 (CH
2
), 15.1 (CH
), 418.3 (100, MH ). HRMS calcd for C26
707, 1686, 1642, 1331, 1204, 1031, 756. Minor Isomer 31cA clear oil (26%): H NMR (300 MHz, CDCl
0H), 5.92 (d, J = 8.1 Hz, 1H), 5.78 (d, J = 8.1 Hz, 1H), 4.95 (br s, 1H), 3.26 (m , 1H), 2.00 (s, 3H), 1.80 (m
H), 1.38-1.22 (m, 3H), 0.95 (t, J = 6.8 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl ) δ 200.1 (C), 172.5 (C), 168.4 (C), 153.4
3
), 13.9 (CH
3
), 8.2 (CH
3
). LRMS m/z (%): 852.2 (20, 2×M+NH
4
), 435.5
+
+
+
−1
25, M+NH
4
H27NNaO : 440.1838. Found: 440.1833. IR (cm ): 3035, 2927, 1776,
4
1
1
1
3
3
) δ 7.16-6.95 (m,
, 1H), 1.65 (s,
c
c
1
3
3
(
(
(
C), 133.83 (C), 133.81 (C), 133.1 (C), 128.3 (CH), 128.0 (CH), 127.90 (CH), 127.86 (CH), 126.8 (CH), 126.3 (CH), 79.8
CH), 63.1 (CH), 56.7 (CH), 45.9 (CH), 34.1 (CH ), 20.7 (CH ), 15.0 (CH ), 14.0 (CH ), 8.2 (CH ). LRMS m/z (%): 435.5
: 440.1838. Found: 440.1833. IR (cm ): 2928, 1778, 1690,
2
2
3
3
3
+
+
+
−1
10, M+NH
4 4
), 418.4 (100, MH ). HRMS calcd for C26H27NNaO
1
643, 1341, 1183, 1041, 729, 697.
S-18

H
H
O
N
O
O
O
O
O
N
H
H
O
O
3
aS,8aR)-3-[(1S,5S)-3,4-Dimethyl-2-oxo-5-propylcyclopent-3-enecarbonyl]-3,3a,8,8a-tetrahydro-2H-indeno[1,2-
d]oxazol-2-one (31dC)
Conditions A: The reaction was performed as described for 31aC using 30d giving 31dA and 31dC after flash
1
chromatography (silica gel, 50:50:7 hexane / dichloromethane / diethyl ether). Major isomer 31dC clear oil (70%): H NMR
(
1
300 MHz, CDCl
3
) δ 7.61 (d, J = 7.5 Hz, 1H), 7.40-7.24 (m, 3H), 5.92 (d, J = 6.7 Hz, 1H), 5.35 (ddd, J = 6.7, 4.5, 2.4 Hz,
, 1H), 1.71 (s, 3H), 1.39-1.21 (m, 3H), 0.88 (t, J = 7.2
) δ 201.0 (C), 173.2 (C), 169.6 (C), 153.0 (C), 139.5 (C), 139.2 (C), 133.9 (C),
), 33.8 (CH ), 20.3
), 354.2 (100, MH ).
H), 4.86 (d, J = 3.3 Hz, 1H), 3.47-3.32 (m, 3H), 2.07 (s, 3H), 1.80 (m
c
13
Hz, 3H). C NMR (JMOD, 75 MHz, CDCl
1
(
HRMS calcd for C21
7
1
3
29.7 (CH), 128.0 (CH), 126.9 (CH), 125.2 (CH), 78.1 (CH), 63.8 (CH), 56.0 (CH), 46.4 (CH), 37.6 (CH
2
2
+
+
+
CH
2
), 15.1 (CH
3
), 13.8 (CH
3
), 8.2 (CH
3
4 4
). LRMS m/z (%): 724.3 (30, 2×M+NH ), 371.2 (10, M+NH
+
−1
H
4
23NNaO : 376.1525. Found: 376.1520. IR (cm ): 2928, 1776, 1686, 1643, 1360, 1183, 1043, 755,
1
27. Minor isomer 31dA lightly tanned solid (23%). Mp = 130-132 °C). H NMR (300 MHz, CDCl
H), 7.36-7.20 (m, 3H), 6.00 (d, J = 7.2 Hz, 1H), 5.31 (dt, J = 7.2, 3.9 Hz, 1H), 4.81, (br s, 1H), 3.41 (d, J = 3.9 Hz, 2H), 3.26
3
) δ 7.48 (d, J = 7.5 Hz,
13
(
m
c
, 1H), 2.05 (s, 3H), 1.81 (m
CDCl ) δ 200.7 (C), 172.0 (C), 170.4 (C), 152.8 (C), 139.1 (C), 138.6 (C), 134.4 (C), 129.8 (CH), 128.2 (CH), 127.2 (CH),
24.9 (CH), 77.9 (CH), 63.1 (CH), 56.0 (CH), 46.9 (CH), 37.9 (CH ), 33.9 (CH ), 20.3 (CH ), 15.0 (CH ), 14.1 (CH ), 8.2
), 354.3 (100, MH ). HRMS calcd for C21
c
, 1H), 1.68 (s, 3H), 1.44-1.24 (m, 3H), 0.95 (t, J = 7.1 Hz, 3H). C NMR (JMOD, 75 MHz,
3
1
(
2
2
2
3
3
+
+
+
+
CH
3
). LRMS m/z (%): 724.5 (25, 2×M+NH
4
), 371.4 (20, M+NH
4
H
23NNaO
4
:
−1
3
76.1525. Found: 376.1522. IR (cm ): 2925, 1757, 1710, 1686, 1643, 1364, 1190, 1034, 753.
O
O
O
O
O
Ph
O
N
N
Ph
O
O
O
O
(
S)-3-[(5S,6S)-7-Oxo-5-propyl-2,3,4,5,6,7-hexahydrocyclopenta[b]pyran-6-carbonyl]-4-phenyloxazolidin-2-one (31eC)
Conditions A: The reaction was performed as described for 31aC using 30e giving 31eA and 31eC, except that only 2
equivalents of MeSO H were used and the aqueous NaHCO (5% w/v) was added immediately after the reaction was warmed
3
3
to room temperature over 2 h. After flash chromatography (silica gel, sequential elution 5:5:1 / 5:5:2 hexane /
1
dichloromethane / diethyl ether) the title compound 31eC was obtained as a white solid (65%). Mp = 178-180 °C. H NMR
(300 MHz, CDCl ) δ 7.41-7.22 (m, 5H), 5.43 (dd, J = 8.4, 2.7 Hz, 1H), 4.86 (d, J = 1.8 Hz, 1H), 4.75 (t, J = 8.7 Hz, 1H), 4.29
3
(
1
dd, J = 8.7, 2.7 Hz, 1H), 4.17-3.99 (m, 2H), 3.05 (m
.93 (quintet, J = 5.7 Hz, 2H), 1.70 (m , 1H), 1.40-1.10 (m, 3H), 0.83 (t, J = 7.2 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl
δ 193.2 (C), 168.6 (C), 153.7 (C), 148.9 (C), 148.6 (C), 139.2 (C), 129.1 (CH), 128.7 (CH), 125.8 (CH), 69.9 (CH ), 66.9
). LRMS m/z (%): 756.5
: 392.1474. Found: 392.1468. IR
c
, 1H), 2.40 (dt, J = 18.9, 6.8 Hz, 1H), 2.24 (dt, J = 18.9, 5.5 Hz, 1H),
1
3
c
3
)
2
(
(
(
CH
2
), 58.1 (CH), 54.6 (CH), 41.7 (CH), 34.3 (CH
2
), 22.3 (CH
2
), 21.4 (CH
), 370.3 (100, MH ). HRMS calcd for C21
cm ): 2927, 1777, 1712, 1692, 1646, 1350, 1202, 1071, 762, 701. Minor isomer 31eA waxy solid (27%): H NMR (300
) δ 7.43-7.25 (m, 5H), 5.49 (dd, J = 9.0, 6.2 Hz, 1H), 4.93 (br s, 1H), 4.74 (t, J = 9.0 Hz, 1H), 4.25 (dd, J = 8.9,
.2 Hz, 1H), 4.15-4.00 (m, 2H), 3.25 (m , 1H), 2.43 (dt, J = 18.6, 6.6 Hz, 1H), 2.24 (dt, J = 18.9, 5.6 Hz, 1H), 1.94 (quintet, J
2 2 3
), 20.2 (CH ), 13.9 (CH
+
+
+
+
20, 2×M+NH
4
), 387.4 (20, M+NH
4
H23NNaO
5
−
1
1
MHz, CDCl
6
3
c
1
3
=
1
6.0 Hz, 2H), 1.73 (m
c
, 1H), 1.42-1.27 (m, 3H), 0.95 (t, J = 7.1 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl
), 66.8 (CH
). LRMS m/z (%): 756.3 (15,
×M+NH ), 387.2 (35, M+NH ), 370.1 (100, MH ). HRMS calcd for C H NNaO : 392.1474. Found: 392.1467. IR
3
) δ 191.8 (C),
68.1 (C), 153.8 (C), 148.3 (C), 148.2 (C), 137.9 (C), 129.2 (CH), 128.6 (CH), 126.0 (CH), 69.8 (CH
2
2
), 58.7
(CH), 55.4 (CH), 40.1 (CH), 34.5 (CH ), 22.3 (CH ), 21.4 (CH ), 20.5 (CH ), 14.1 (CH
2
2
+
2
2
3
+
+
+
2
4
4
21 23
5
−1
(cm ): 3033, 2930, 1776, 1713, 1694, 1645, 1356, 1200, 1067, 700.
S-19

O
N
O
O
O
O
Ph
O
N
Ph
MeO
O
MeO
O
(S)-3-[(1S,2S)-5-Methoxy-3-oxo-1-propyl-2,3-dihydro-1H-indene-2-carbonyl]-4-phenyloxazolidin-2-one (31fC)
Conditions A: The reaction was performed as described for 31aC using 30f giving 31fA and 31fC after flash chromatography
(
(
silica gel, sequential elution 20:20:1 / 10:10:1 hexane / dichloromethane / diethyl ether). Major isomer 31fC white solid
43%). Mp = 166-168 °C. H NMR (300 MHz, CDCl ) δ 7.41-7.30 (m, 6H), 7.20 (dd, J = 8.4, 2.6 Hz, 1H), 7.13 (d, J = 2.6
3
1
Hz, 1H), 5.49 (dd, J = 8.4, 2.8 Hz, 1H), 5.14 (d, J = 4.2 Hz, 1H), 4.81 (t, J = 8.7 Hz, 1H), 4.35 (dd, J = 8.9, 2.8 Hz, 1H), 3.83
1
3
(
s, 3H), 3.74 (m
CDCl ) δ 198.7 (C), 168.3 (C), 159.7 (C), 153.8 (C), 150.2 (C), 139.1 (C), 135.9 (C), 129.1 (CH), 128.6 (CH), 125.8 (CH),
25.7 (CH), 124.4 (CH), 105.3 (CH), 69.9 (CH ), 59.6 (CH), 58.1 (CH), 55.5 (CH ), 41.5 (CH), 36.6 (CH ), 20.7 (CH ), 13.8
: 394.1654. Found: 394.1665.
c c c
, 1H), 1.93 (m , 1H), 1.57 (m , 1H), 1.37-1.18 (m, 2H), 0.86 (t, J = 7.2 Hz, 3H). C NMR (JMOD, 75 MHz,
3
1
(
2
3
2
2
+
+
+
CH
IR (cm ): 2923, 1778, 1712, 1685, 1490, 1344, 1229, 1201, 759. Minor Isomer 31fA thick oil (26%): H NMR (300 MHz,
CDCl ) δ 7.47-7.28 (m, 6H), 7.20 (dd, J = 8.4, 2.7 Hz, 1H), 7.11 (d, J = 2.7 Hz, 1H), 5.52 (dd, J = 9.0, 5.7 Hz, 1H), 5.18 (br s,
H), 4.77 (t, J = 9.0 Hz, 1H), 4.29 (dd, J = 9.0, 5.7 Hz, 1H), 3.85 (m , 1H), 3.81 (s, 3H), 1.96 (m , 1H), 1.58 (m , 1H), 1.44-
.31 (m, 2H), 0.96 (t, J = 7.4 Hz, 3H). C NMR (JMOD, 75 MHz, CDCl ) δ 197.6 (C), 168.0 (C), 159.6 (C), 153.7 (C),
49.9 (C), 138.1 (C), 135.8 (C), 129.0 (CH), 128.5 (CH), 125.9 (CH), 125.8 (CH), 124.4 (CH), 105.3 (CH), 69.8 (CH ), 60.1
), 40.5 (CH), 36.8 (CH ), 20.8 (CH ), 14.0 (CH ). LRMS m/z (%): 804.2 (25, 2×M+NH
3 4 5
). LRMS m/z (%): 411.5 (10, M+NH ), 394.5 (100, MH ). HRMS calcd for C23H24NO
−1
1
3
1
1
1
c
c
c
1
3
3
2
+
4
(br s, CH), 58.4 (CH), 55.5 (CH
3
2
2
3
),
4 5
), 394.5 (100, MH ). HRMS calcd for C23H24NO : 394.1654. Found: 394.1641. IR (cm ): 2925, 1776,
+
+
+
−1
4
1
11.3 (40, M+NH
715, 1691, 1491, 1321, 1277, 1196, 1024, 699.
O
O
N
O
O
O
Ph
N
O
Ph
O
O
O
O
Ph
Ph
(S)-3-[(5S,6R)-7-Oxo-5-phenyl-2,3,4,5,6,7-hexahydrocyclopenta[b]pyran-6-carbonyl]-4-phenyloxazolidin-2-one (31hA)
Conditions B: The reaction was performed as described for 31gA using 30h giving 31hA and 31hC after flash
chromatography (silica gel, sequential elution 50:50:7 / 50:50:12 hexane / dichloromethane / diethyl ether). Major isomer
1
3
1hA white solid (48%). Mp = 102-104 °C. H NMR (300 MHz, CDCl
3
) δ 7.44-7.26 (m, 8H), 7.18 (d. J = 7.8 Hz, 2H), 5.43
(
2
(
5
dd, J = 8.9, 6.2 Hz, 1H), 5.16 (s, 1H), 4.66 (t, J = 9.0 Hz, 1H), 4.43 (s, 1H), 4.21 (dd, J = 8.9, 6.2 Hz, 1H), 4.15-4.05 (m, 2H),
13
.13-2.05 (m, 2H), 1.93-1.84 (m, 2H). C NMR (JMOD, 75 MHz, CDCl
C), 139.7 (C), 138.1 (C), 129.2 (CH), 129.1 (CH), 128.6 (CH), 127.7 (CH), 127.6 (CH), 126.0 (CH), 69.8 (CH
3
) δ 191.6 (C), 167.1 (C), 153.4 (C), 148.8 (C), 146.9
), 67.1 (CH ),
), 404.4 (100, MH ). HRMS
5
H21NNaO : 426.1317. Found: 426.1304. IR (cm ): 2926, 1778, 1716, 1695, 1648, 1333, 1201, 1109, 1055, 702.
2
2
+
+
2 2 4
8.9 (CH), 58.5 (CH), 45.7 (CH), 22.2 (CH ), 21.3 (CH ). LRMS m/z (%): 421.3 (30, M+NH
+
−1
calcd for C24
Minor isomer 31hC (8%). Mp = 68-70°C. H NMR (300 MHz, CDCl
1
3
) δ 7.41-7.22 (m, 8H), 7.10 (dd, J = 7.8, 1.5 Hz, 2H),
5
2
.42 (dd, J = 8.4, 2.8 Hz, 1H), 5.13 (d, J = 2.7 Hz, 1H), 4.74 (t, J = 8.6 Hz, 1H), 4.26 (dd, J = 8.7, 2.8 Hz, 1H), 4.24 (d, J =
13
.7 Hz, 1H), 4.17-4.09 (m, 2H), 2.16-2.07 (m, 2H), 1.98-1.86 (m, 2H). C NMR (JMOD, 75 MHz, CDCl
3
) δ 192.8 (C), 167.7
(
1
C), 153.5 (C), 149.2 (C), 147.5 (C), 139.5 (C), 139.0 (C), 129.2 (CH), 129.1 (CH), 128.7 (CH), 127.7 (CH), 127.6 (CH),
25.8 (CH), 70.0 (CH ), 67.1 (CH ), 58.3 (CH), 58.0 (CH), 47.0 (CH), 22.3 (CH ), 21.3 (CH ). LRMS m/z (%): 421.5 (40,
: 426.1317. Found: 426.1313. IR (cm ): 3030, 2926, 1777,
2
2
2
2
+
+
+
−1
M+NH
4 5
), 404.4 (100, MH ). HRMS calcd for C24H21NNaO
1
718, 1694, 1647, 1197, 1108, 1072, 700.
O
O
O
O
O
Ph
N
O
N
Ph
O
O
O
O
Ph
Ph
(S)-3-[(5S,6S)-7-Oxo-5-phenyl-2,3,4,5,6,7-hexahydrocyclopenta[b]pyran-6-carbonyl]-4-phenyloxazolidin-2-one (31hB)
S-20

Conditions C: The reaction was performed as described for 31aC using 30h except that the reaction was warmed to 0 °C and
stirred at this temperature for 0.5 h, then the aqueous NaHCO (5% w/v) added. After flash chromatography (silica gel, 1:1
hexanes / ethyl acetate) the product 31hB was obtained as a white solid (64%). Mp = 100-102 °C. H NMR (600 MHz,
CDCl ) 7.38 (m , 1H), 7.20-6.95 (m, 7H), 6.53 (d, J = 7.5 Hz, 2H), 5.20 (dd, J = 8.6, 2.9 Hz, 1H), 4.79 (d, J = 7.5 Hz, 1H),
.58-4.48 (m, 2H), 4.20-4.05 (m, 3H), 2.10 (m
C), 166.9 (C), 153.6 (C), 151.3 (C), 147.1 (C), 137.8 (C), 135.7 (C), 129.1 (CH), 128.7 (CH), 128.5 (CH), 127.9 (CH), 127.6
3
1
3
c
1
3
4
c
, 1H), 2.01 (m
c
, 1H), 1.97-1.80 (m, 2H). C NMR (100 MHz, CDCl
3
)  194.8
(
(
C
CH), 125.4 (CH), 70.4 (CH
2
), 66.9 (CH
2
), 57.5 (CH), 54.8 (CH), 47.7 (CH), 22.1 (CH ), 21.2 (CH ). HRMS calcd for
2 2
+
24
H
22NO
5
: 404.1492. Found: 404.1476.
O
O
O
O
O
Ph
N
N
O
Ph
MeO
O
MeO
O
Ph
Ph
(
S)-3-[(1S,2R)-5-Methoxy-3-oxo-1-phenyl-2,3-dihydro-1H-indene-2-carbonyl]-4-phenyloxazolidin-2-one (31iA)
Conditions A: The reaction was performed as described for 31aC using 30i except only 5 equivalents of MeSO H were used,
giving 31iA and 31iC after flash chromatography (silica gel, 50:50:6 hexane / dichloromethane / diethyl ether). Major isomer
3
1
3
5
7
1iA white solid (68%). Mp = 80-82 °C. H NMR (300 MHz, CDCl
.48 (br s, 1), 5.07 (d, J = 5.7 Hz, 1H), 4.70 (t, J = 9.0 Hz, 1H), 4.27 (dd, J = 8.9, 5.6 Hz, 1H), 3.84 (s, 3H). C NMR (JMOD,
5 MHz, CDCl ) δ 196.9 (C), 166.9 (C), 159.9 (C), 153.5 (C), 148.6 (C), 141.5 (C), 138.3 (C), 135.7 (C), 129.1 (CH), 128.9
), 64.0 (CH), 58.3
3
) δ 7.50-7.05 (m, 13H), 5.48 (dd, J = 9.2, 5.6 Hz, 1H),
1
3
3
(
(
CH), 128.5 (CH), 128.1 (CH), 127.4 (CH), 127.1 (CH), 125.9 (CH), 124.7 (CH), 105.1 (CH), 69.8 (CH
2
+
+
+
CH), 55.6 (CH
3
), 46.0 (CH). LRMS m/z (%): 872.4 (25, 2×M+NH
4
), 445.3 (40, M+NH
4
), 428.3 (100, MH ). HRMS calcd
+
−1
for C26
H
21NNaO
5
: 450.1317. Found: 450.1314. IR (cm ): 2923, 1778, 1718, 1692, 1489, 1333, 1279, 1023, 699. Minor
1
isomer 31iC thick oil (5%): H NMR (300 MHz, CDCl ) δ 7.40-7.08 (m, 13H), 5.50 (dd, J = 8.4, 2.9 Hz, 1H), 5.46 (d, J = 5.0
Hz, 1H), 4.97 (d, J = 5.0 Hz, 1H), 4.79 (t, J = 8.7 Hz, 1H), 4.29 (dd, J = 8.9, 2.9 Hz, 1H), 3.86 (s, 3H). C NMR (JMOD, 75
3
1
3
MHz, CDCl
3
) δ 198.1 (C), 167.6 (C), 160.1 (C), 153.7 (C), 149.0 (C), 141.4 (C), 138.9 (C), 136.0 (C), 129.2 (CH), 129.0
), 63.4 (CH), 58.3
), 47.2 (CH). LRMS m/z (%): 450.1 (20, M+Na ), 428.3 (100, MH ), 265.2 (40). HRMS calcd for
(
(
CH), 128.7 (CH), 128.0 (CH), 127.5 (CH), 127.4 (CH), 125.8 (CH), 124.9 (CH), 105.3 (CH), 70.1 (CH
2
CH), 55.7 (CH
+
+
3
+
−1
C
26
H
21NNaO
5
: 450.1317. Found: 450.1310. IR (cm ): 2925, 1779, 1719, 1692, 1490, 1280, 1194, 1024.
(S)-3-[(4S,5R)-1-Benzyl-6-oxo-4-phenyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-5-carbonyl]-4-phenyloxazolidin-2-one
(
31jA)
Cupric triflate (76mg, 0.21 mmol) was added to a stirred solution of 30j (100 mg, 0.21 mmol) in dichloromethane (10 mL),
the reaction mixture was then heated at reflux for 4 h. After this time the reaction was cooled to 18 °C and quenched with
aqueous NaHCO
mL), the combined organic extracts were dried over MgSO
1jB and 31jC were isolated after flash chromatography (silica gel, 3:1 then 3:2 hexanes / ethyl acetate). Major isomer 31jA,
3
(5% w/v). The phases were separated and the aqueous phase re-extracted with dichloromethane (2 × 10
4
and concentrated under reduced pressure. The products 31jA,
3
1
clear gum (51 mg, 51%). H NMR (400 MHz, CDCl
3
) 7.46 (d, J = 7.2 Hz, 2H), 7.40-7.20 (m, 13H), 7.01 (d, J = 2.2 Hz,
1
1
H), 5.98 (d, J = 2.2 Hz, 1H), 5.62 (br s, 1H), 5.49 (dd, J = 9.2, 5.6 Hz, 1H), 5.29 (d, J = 14.8 Hz, 1H), 5.25 (d, J = 14.8 Hz,
1
3
H), 4.99 (d, J = 3.6 Hz, 1H), 4.67 (t, J = 9.0 Hz, 1H), 4.21 (dd, J = 8.8, 5.6 Hz, 1H). C NMR (100 MHz, CDCl )  181.9
3
(
(
(
C), 167.9 (C), 153.5 (C), 153.2 (C), 141.4 (C), 138.3 (C), 136.6 (C), 135.0 (CH), 131.3 (C), 129.0 (CH), 128.8 (CH), 128.7
CH), 128.4 (CH), 128.0 (CH), 127.8 (CH), 127.5 (CH), 127.1 (CH), 126.0 (CH), 106.1 (CH), 69.7 (CH ), 67.2 (CH), 58.5
: 477.1809. Found: 477.1818. cis-Isomer 31jB white solid (16
2
+
2 25 2 4
CH), 50.9 (CH ), 41.4 (CH). HRMS calcd for C30H N O
1
3
mg, 16%, characterised in following experiment). Minor Isomer 31jC thick gum (18 mg, 18%): H NMR (400 MHz, CDCl )
7.44-7.22 (m, 13H), 7.14 (dd, J = 7.8, 1.4 Hz, 2H), 7.05 (d, J = 2.2 Hz, 1H), 6.03 (d, J = 2.2 Hz, 1H), 5.59 (d, J = 3.6 Hz,
1
H), 5.50 (dd, J = 8.2, 2.7 Hz, 1H), 5.28 (s, 2H), 4.88 (d, J = 3.6 Hz, 1H), 4.76 (t, J = 8.6 Hz, 1H), 4.28 (dd, J = 8.8, 2.7 Hz,
S-21

13
1
H). C NMR (100 MHz, CDCl
3
)  183.0 (C), 168.3 (C), 153.60 (C), 153.59 (C), 141.2 (C), 139.1 (C), 136.6 (C), 135.3
(
(
CH), 131.6 (C), 129.2 (CH), 128.9 (CH), 128.7 (CH), 128.6 (CH), 128.1 (CH), 127.9 (CH), 127.3 (CH), 127.1 (CH), 125.7
+
CH), 106.3 (CH), 69.9 (CH
2
2 25 2 4
), 66.6 (CH), 58.2 (CH), 51.0 (CH ), 42.4 (CH). HRMS calcd for C30H N O : 477.1809.
Found: 477.1820.
O
O
O
O
O
Ph
N
N
O
Ph
Bn
Bn
N
N
O
O
Ph
Ph
(S)-3-[(4S,5S)-1-Benzyl-6-oxo-4-phenyl-1,4,5,6-tetrahydrocyclopenta[b]pyrrole-5-carbonyl]-4-phenyloxazolidin-2-one
(31jB)
Conditions C: The reaction was performed as described for 31aC using 30j except that the reaction was warmed to 0 °C and
stirred at this temperature for 2 h, then the aqueous NaHCO (5% w/v) added. The products 31jB and 31jD were isolated after
flash chromatography (silica gel, 3:2 hexanes / ethyl acetate). Major isomer 31jB white solid (81%). Mp = 88-90 °C. H
NMR (400 MHz, CDCl ) 7.40-7.28 (m, 5H), 7.16 (t, J = 7.4 Hz, 1H), 7.13-7.02 (m, 7H), 7.01 (d, J = 2.4 Hz, 1H), 6.53 (d, J
7.6 Hz, 2H), 5.88 (d, J = 2.4 Hz, 1H) 5.39 (d, J = 7.6 Hz, 1H), 5.35 (d, J = 14.8 Hz, 1H), 5.29 (d, J = 14.8 Hz, 1H), 5.23
3
1
3
=
13
(dd, J = 8.8, 3.3 Hz, 1H), 4.99 (d, J = 7.6 Hz, 1H) 4.57 (t, J = 8.8 Hz, 1H), 4.10 (dd, J = 9.0, 3.3 Hz, 1H). C NMR (100
MHz, CDCl
3
)  185.2 (C), 168.1 (C), 154.4 (C), 153.6 (C), 138.2 (C), 138.1 (C), 136.7 (C), 135.2 (CH), 133.9 (C), 129.3
(
7
CH), 128.72 (CH), 128.69 (CH), 128.0 (CH), 127.9 (CH), 127.8 (CH), 127.6 (CH), 127.4 (CH), 125.4 (CH), 104.7 (CH),
+
0.2 (CH
2
), 63.8 (CH), 57.6 (CH), 50.8 (CH
2
), 43.5 (CH). HRMS calcd for C30
25 2 4
H N O : 477.1809. Found: 477.1807. Minor
1
Isomer 31jD thick gum (10%): H NMR (600 MHz, CDCl
3
) 7.40-7.25 (m, 11H), 7.23-7.17 (m, 2H), 7.14 (d, J = 6.6 Hz,
2
H), 7.03 (d, J = 2.4 Hz, 1H), 5.92 (d, J = 2.4 Hz, 1H), 5.59 (d, J = 7.2 Hz, 1H), 5.36 (d, J = 14.7 Hz, 1H), 5.27 (d, J = 14.7
1
3
Hz, 1H) 4.87 (d, J = 7.2 Hz, 1H) 4.40 (dd, J = 8.6, 2.8 Hz, 1H), 3.97 (dd, J = 8.4, 2.8 Hz, 1H), 3.77 (t, J = 8.4 Hz, 1H). C
NMR (100 MHz, CDCl
3
)  184.8 (C), 168.2 (C), 153.4 (C), 153.2 (C), 139.3 (C), 138.6 (C), 136.8 (C), 135.1 (CH), 130.5
(
1
4
C), 129.3 (CH), 129.1 (CH), 128.9 (CH), 128.6 (CH), 128.3 (CH), 128.12 (CH), 128.06 (CH), 127.6 (CH), 125.8 (CH),
+
05.8 (CH), 69.8 (CH
77.1822.
2
2 25 2 4
), 64.3 (CH), 57.4 (CH), 51.1 (CH ), 43.4 (CH). HRMS calcd for C30H N O : 477.1809. Found:
O
O
O
O
N
O
N
O
O
O
Ph
Ph
(S)-3-[(1R,5S)-3,4-Dimethyl-2-oxo-5-phenylcyclopent-3-enecarbonyl]-4-isopropyloxazolidin-2-one (31kA)
Conditions B: The reaction was performed as described for 31gA using 30j giving 31kA and 31kC after flash
1
chromatography (silica gel, 50:50:4 hexane / dichloromethane / diethyl ether). Major isomer 31kA thick oil (50%): H NMR
(
2
(
(
(
3
300 MHz, CDCl
H), 2.35 (sept.d, J = 6.9, 3.8 Hz, 1H), 1.85 (s, 3H), 1.79 (s, 3H), 1.01 (d, J = 6.9 Hz, 3H), 0.92 (d, J = 6.9 Hz, 3H). C NMR
JMOD, 75 MHz, CDCl ) δ 200.7 (C), 171.0 (C), 168.4 (C), 153.7 (C), 140.2 (C), 134.6 (C), 129.1 (CH), 128.0 (CH), 127.5
CH), 63.1 (CH ), 60.3 (CH), 58.7 (CH), 51.7 (CH), 28.3 (CH), 17.9 (CH ), 15.4 (CH ), 14.5 (CH ), 8.6 (CH ). LRMS m/z
%): 700.4 (15, 2×M+NH ), 342.2 (100, MH ). HRMS calcd for C20 : 364.1525. Found:
64.1521. IR (cm ): 2964, 1778, 1707, 1687, 1647, 1371, 1203, 1083, 702.. Minor isomer thick oil 31kC (23%): H NMR
) δ 7.38-7.24 (m, 3H), 7.15 (d, J = 7.5 Hz, 2H), 5.16 (d, J = 3.3 Hz, 1H), 4.44 (br s, 1H), 4.39-4.15 (m, 3H),
3
) δ 7.37-7.25 (m, 3H), 7.16 (d, J = 7.5 Hz, 2H), 5.23 (d, J = 3.3 Hz, 1H), 4.51-4.42 (m, 2H), 4.27-4.19 (m,
13
3
2
3
3
3
3
+
+
+
+
4
), 359.4 (10, M+NH
4
H23NNaO
4
−1
1
(300 MHz, CDCl
3
13
2
.32 (m
c
, 1H), 1.86 (s, 3H), 1.78 (s, 3H), 0.92 (d, J = 6.9 Hz, 3H), 0.85 (d, J = 6.9 Hz, 3H). C NMR (JMOD, 75 MHz,
) δ 201.0 (C), 171.7 (C), 168.2 (C), 154.2 (C), 140.1 (C), 134.6 (C), 129.1 (CH), 127.9 (CH), 127.6 (CH), 63.8 (CH ),
). LRMS m/z (%): 700.3 (20,
: 364.1525. Found: 364.1520. IR
CDCl
5
2
3
2
9.9 (CH), 59.8 (CH), 52.0 (CH), 29.3 (CH), 18.1 (CH
3
), 15.5 (CH
3
), 15.2 (CH
3
), 8.5 (CH
3
+
+
+
+
×M+NH
4
), 359.3 (15, M+NH
4
), 342.2 (100, MH ). HRMS calcd for C20
H
23NNaO
4
−1
(cm ): 2964, 1778, 1708, 1688, 1646, 1370, 1200, 1078, 703.
S-22

1
,1-Dibromo-3-methylbut-1-ene (33)
Triphenylphosphine (28.9 g, 109 mmol) was added to a stirred solution of carbon tetrabromide (36.6 g, 109 mmol) in dry
dichloromethane (350 mL) at 0 °C. Zinc dust (14.6 g, 219 mmol) was then added and the resultant mixture was allowed to
warm to room temperature and was stirred under N for 18 hours. After this time isobutyrylaldehyde (5.1 mL, 55 mmol) was
2
added and the mixture was stirred for 4 hours. An additional portion of isobutyrylaldehyde (5.1 mL, 55 mmol) was then
added with stirring continued for a further 2 hours. After this time the mixture was filtered through celite and the liquid
collected was concentrated under reduced pressure. The crude product was then extracted from the resultant sludge with a 1:1
mixture of dichloromethane and hexane, (5  50 mL, dichloromethane added first). The combined extracts were concentrated
under reduced pressure and flash chromatographed (silica gel, 17:3 hexane / dichloromethane) to return the title compound as
1
a clear liquid (14.6 g, 59%). H NMR (300 MHz, CDCl
3
) 6.22 (d, J = 9.0 Hz, 1H), 2.58 (dsept., J = 9.0, 6.9 Hz, 1H), 1.03
(
d, J = 6.9 Hz, 6H).
(R)-3-(4-Methylpent-2-ynoyl)-4-phenyloxazolidin-2-one (35)
Butyllithium (2.0 M in cyclohexane, 5.0 mL, 10.0 mmol) was added dropwise to a stirred solution of dibromo-olefin 33 (1.14
g, 5.00 mmol) in tetrahydrofuran (15 mL) at −78 °C under nitrogen. After stirring for 30 minutes the nitrogen was turned off
and carbon dioxide was bubbled slowly through the solution while it was warmed to 0ºC (ice bath) over the course of 30
minutes. The carbon dioxide supply was then removed and replaced with the nitrogen atmosphere. The solution was again
cooled to -78 °C and pivaloyl chloride (635 μL, 5.00 mmol) was added. The solution was then allowed to warm to room
temperature and was stirred for 3 hours. The solution was then cooled again to -78 °C and to it was added via cannula a
solution of lithiated oxazolidinone (5.00 mmol, generated by addition of 2.5 mL of 2.0 M butyllithium solution to 816 mg of
R-phenyloxazolidinone 34 in 30 mL of tetrahydrofuran) at −78ºC. The solution was then allowed to warm to room
temperature and stirred for 2 hours. After this time the solution was concentrated to a volume of 10 mL under vacuum. Ethyl
acetate (30 mL) and distilled water (30 mL) were then added and the organic phase was separated, the aqueous phase was re-
4
extracted with ethyl acetate (2 × 20 mL) and the combined organic extracts were dried over MgSO and concentrated onto
silica gel (3 g) under reduced pressure. The solid residue was subjected to flash chromatography (silica gel, 83:17 hexane /
1
ethyl acetate) giving the title compound as a thick oil (887 mg, 69%). H NMR (300 MHz, CDCl
3
) 45-7.25 (m, 5H), 5.43
(
dd, J = 8.7, 3.6 Hz, 1H), 4.67 (app. t, J = 8.7 Hz, 1H), 4.27 (dd, J = 9.0, 3.6 Hz, 1H), 2.77 (sept, J = 6.9 Hz, 1H), 1.26 (d, J
app
1
3
=
1
6.9 Hz, 6H). C NMR (JMOD, 75 MHz, CDCl
3
)  152.2 (C), 150.4 (C), 138.4 (C), 129.2 (CH), 128.9 (CH), 126.0 (CH),
+
03.2 (C), 72.8 (C), 69.8 (CH
2
), 57.6 (CH), 21.5 (2×CH
3
), 21.1 (CH). LRMS m/z (%): 532.2 (10, 2×M+NH
4
), 275.2 (60,
+
+
+
−1
M+NH
4
), 258.2 (100, MH ). HRMS calcd for C15
H
15NNaO
3
: 280.0950. Found: 280.0941. IR (cm ): 3034, 2976, 2231,
1
789, 1664, 1319, 1195, 1056, 712.
(R,Z)-1-(1-Benzyl-1H-pyrrol-2-yl)-2-(2-methylpropylidene)-3-(2-oxo-4-phenyloxazolidin-3-yl)propane-1,3-dione (36)
Alkyne 35 was reacted with acid chloride 15i in accordance with General Procedure A giving the product 36 after flash
1
3
chromatography (silica gel, 4:1 hexane / ethyl acetate) as a tan solid (91%). Mp = 60-62 °C. H NMR (300 MHz, CDCl )

4
3
45-7.20 (m, 8H), 7.15 (d, J = 6.9 Hz, 2H), 7.94-6.85 (m, 2H), 6.58 (d, J = 10.5 Hz, 1H), 6.17 (m
c
, 1H), 5.55-5.42 (m, 3H),
.69 (app. t, Japp = 8.7 Hz, 1H), 4.22 (dd, J = 8.7, 4.2 Hz, 1H), 2.47 (m , 1H), 1.07 (d, J = 6.6 Hz, 3H), 1.02 (d, J = 6.3 Hz,
c
1
3
H). C NMR (JMOD, 75 MHz, CDCl
3
)  182.2 (C), 165.7 (C), 153.9 (CH), 153.0 (C), 138.7 (C), 138.2 (C), 136.3 (C),
S-23

1
30.1 (CH), 129.3 (C), 129.0 (CH), 128.6 (CH), 128.5 (CH), 127.42 (CH), 127.35 (CH), 126.0 (CH), 122.0 (CH), 108.7
+
(CH), 70.3 (CH
2
), 57.5 (CH), 51.9 (CH
2
), 29.7 (CH), 21.94 (CH
3
), 21.91 (CH
3 4
). LRMS m/z (%): 902.5 (10, 2×M+NH ),
+
+
−1
4
1
43.4 (100, MH ). HRMS calcd for C27
319, 1201, 1083, 699.
H N O : 443.1971. Found: 443.1983. IR (cm ): 2964, 1782, 1692, 1614, 1385,
27 2 4
S-24

1
13
IV.
H and C (JMOD or APT) NMR Spectra
Methyl 2-(5,5-dimethyl-3-oxo-cyclohex-1-enyl)-acrylate (16a)
1
3
H NMR (300 MHz, CDCl )
1
3
3
C NMR (APT, 75 MHz, CDCl )
S-25

Methyl (Z)-2-(4-methoxyphenyl)-3-phenyl-acrylate (16b)
1
3
H NMR (300 MHz, CDCl )
1
3
3
C NMR (APT, 75 MHz, CDCl )
S-26

Methyl (Z)-2-(5,5-Dimethyl-3-oxo-cyclohex-1-enyl)-3-phenyl-acrylate (Z-16c)
1
3
H NMR (300 MHz, CDCl )
1
3
3
C NMR (APT, 75 MHz, CDCl )
S-27

Methyl (E)-2-(5,5-Dimethyl-3-oxo-cyclohex-1-enyl)-3-phenyl-acrylate (E-16c)
1
3
H NMR (300 MHz, CDCl )
1
3
3
C NMR (APT, 75 MHz, CDCl )
S-28

Methyl (Z)-2-benzylidine-4-pentenoate (16d)
1
3
H NMR (300 MHz, CDCl )
1
3
3
C NMR (APT, 75 MHz, CDCl )
S-29

Methyl (E)-3-phenyl-2-(3,4,5-trimethoxybenzoyl)-acrylate (E-16e)
1
3
H NMR (300 MHz, CDCl )
1
3
3
C NMR (APT, 75 MHz, CDCl )
S-30