Extending Pummerer reaction chemistry. Examination of the prospects for forming vicinal quaternary carbon centers

Article abstract of DOI:10.1016/j.tetlet.2009.02.024

Pummerer chemistry applied to 2-sulfinyl indoles promotes oxidative cyclization of pendant nucleophiles to furnish C(3) spirocyclic indolenine products. Use of tetrasubstituted silyl enol ether nucleophiles in this transform yields spirocycles featuring v

Full text of DOI:10.1016/j.tetlet.2009.02.024

Tetrahedron Letters 50 (2009) 1914–1916
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Tetrahedron Letters
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Extending Pummerer reaction chemistry. Examination of the prospects for
forming vicinal quaternary carbon centers
*
Ken S. Feldman , Ahmed Yimam Nuriye
Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania 16802, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Pummerer chemistry applied to 2-sulfinyl indoles promotes oxidative cyclization of pendant nucleo-
philes to furnish C(3) spirocyclic indolenine products. Use of tetrasubstituted silyl enol ether nucleophiles
in this transform yields spirocycles featuring vicinal all-carbon quaternary centers in two cases, but fails
when a nearby amine can intervene.
Received 9 January 2009
Revised 3 February 2009
Accepted 4 February 2009
Available online 8 February 2009
Ó 2009 Elsevier Ltd. All rights reserved.
The application of Pummerer reaction chemistry to the problem
of controlled oxidative cyclization of indole and imidazole rings
has led to the efficient syntheses of indolenine and imidazoline
products, respectively (Scheme 1).1,2 The ready acquisition of spi-
rocyclic constructs of the general type 3 can impact on synthesis
studies of cognate natural products, and in fact the imidazole var-
iant of this chemistry is at the core of recent syntheses of the
oroidin-derived sponge alkaloids dibromophakelstatin, dibromo-
phakellin, and dibromoagelaspongin.3 One question left unan-
swered by all of these studies focuses on a very demanding C–C
bond formation; the construction of a bond between two quater-
nary carbon centers. Numerous indole-derived alkaloids contain
this structural feature (e.g., crassanine (4)4), and so the extension
of the Pummerer methodology toward this challenge in C–C bond
formation might prove enabling for that class of targets. In this Let-
ter, the feasibility of accomplishing this goal is established, and
some significant limitations are exposed.
path a
Nu
Nu
N
Nu
X
path b
S+
S+
Ph
(1)
SPh
base
N
H
Ph
N
1
2
3
N
CH3
H3CO2C
H3CO
H3CO
O
N
H
4 crassanine
Scheme 1. Illustrative example of
a
Pummerer reaction-mediated oxidative
spirocyclization.
The extension of this oxidative cyclization chemistry to vicinal
quaternary C–C bond formation is illustrated in Scheme 2. The tet-
rasubstituted silyl enol ethers 9a and 9b were assembled via stan-
dard functional group manipulation chemistry as shown. Silyl enol
ether 9b was formed as the strictly E-alkene (NOE, Scheme 2) in ac-
cord with precedent.5 Exposure of either of the enol ethers 9a or 9b
to typical Pummerer initiation conditions (Tf2O, hindered base)
rapidly furnished spirocyclic products in moderate yields. The
structural assignments of 10a and 10b rested on the striking sim-
ilarity between the 1H and 13C NMR data for these species and
those of the related but less substituted spirocycles prepared ear-
lier,1a,d and on a single crystal X-ray analysis of 10b (see Scheme
3).6
this selectivity might cite competing cyclization transition states
11a and 11b (assuming a vinylogous Pummerer mechanism (path
b, Scheme 1) rather than an additive one (path a, Scheme 1) for
simplicity). The acquisition of 10b rather than 12 then suggests
that the gauche-type interaction illustrated in 11a is more energet-
ically penalizing than any of the other steric interactions that
might arise.
A variant of the Pummerer initiator methodology was explored
briefly, Eq. 2. Stang’s reagent-mediated initiation of the Pummerer
sequence1b on the corresponding sulfide formed by hydrosilylation
of 7a did afford the desired spirocyclic material 10a, but in inferior
yield compared to the sulfoxide/Tf2O initiated process.
O
Spirocycle 10b was formed as a single diastereomer featuring
an equatorial Ph substituent and an axially disposed aryl ring from
the indolenine core. Mechanistic speculation about the basis for
O
CH3
92%
1) PhMe2Si–H
7% Rh(PPh3)3Cl
ð2Þ
CH3
SPh
SPh
2) PhI(CN)OTf
N
H
N
* Corresponding author. Tel.: +1 814 863 4654; fax: +1 814 863 5319.
E-mail address: ksf@chem.psu.edu (K.S. Feldman).
2,6-lutidine
7a
10a
28%
0040-4039/$ - see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2009.02.024

K. S. Feldman, A. Y. Nuriye / Tetrahedron Letters 50 (2009) 1914–1916
1915
1) neat
PhO2S
H3CO2C
CON(Me)OMe
O
1)
CO2CH3
130 oC
N
H
CO2H
+
SPh
2) 10 wt%
Pd black
R
EDCI, DMAP
2) PhSCl, HCl
N
H
N
H
PhO2S
N
N
5
6
CBz
H
MgBr
69%
15
13
14
79%
O
Br
O–
PhO2S
H3CO2C
O
R
R
–
R
O
mCPBA
1) NaOCH3
2) H3CONH(CH3)
LiNTMS2
S+
Ph
S+
SPh
N
N
O
N
Ph
N
N
H
16
H
H
7a R = CH3 91%
7b R = Ph
8a R = CH3 94%
8b R = Ph, 42% from 6
O–
S+
Ph
O–
S+
Ph
3) RMgBr
R = CH3
or Ph
NaHCO3
DMF, 90 oC
N
N
SiPhMe2
H
H
O
O
R
nOe
Tf2O
2,6-lutidine
17
55%
66%
38%
18a R = CH3
18b R = Ph
CH3
SPh
PhMe2Si–H
7% Rh(PPh3)3Cl
–
O
R
O
S+
Ph
N
H
N
R
PhMe2SiO
HMBC's
H
10a
9a
R = CH3 79%
R = CH3 82%
9b R = Ph, 77%
PhMe2Si–H
7% Rh(PPh3)3Cl
N
R
10b R = Ph, 41%
Tf2O
H
H
N
O– 2,6-lutidine
Scheme 2. Synthesis and oxidative cyclization chemistry of tetrasubstituted silyl
enol ethers to form vicinal quaternary centers.10
S+
Ph
SPh
N
N
H
71%
19a R = CH3
19b R = Ph
20a R = CH3
20b R = Ph
45%
10% from 18b
Scheme 4. Synthesis and Pummerer-mediated oxidative cyclization chemistry of a
crassanine model.10
SiMe2Ph
O
OSiMe2Ph
R
N
N
–
R
X
N
+
Tf2O
S+
SPh
19
20
–
PhMe2SiX
R
2,6-lut.
N
Ph
21
22
–
O
SiMe2Ph
Scheme 3. Cyclization transition state analysis; X-ray structure of 10b.
O
R
adventitious
H+
+
N
N
H
–
H
Tf2O
X
Finally, a more complicated substrate relevant to a projected
synthesis of crassanine was investigated, Scheme 4. Both methyl-
and phenyl-substituted silyl enol ethers 19a and 19b (unassigned
geometry), respectively, were prepared from the known Diels–Al-
der precursors 137 and 148 and the sulfoxide 16, which was syn-
thesized from 3-(2-bromoethyl)indole (PhSCl, HCl (94%); mCPBA
(96%)). Submission of either substrate to the optimized Pummerer
initiation conditions led to modest amounts of spirocyclic material
in both cases as apparent 1:1 mixtures of diastereomers, but the 1H
NMR and 13C NMR data of these products were clearly inconsistent
with formation of the desired C–C bonded spirocycle. An unsatu-
rated ketone function was evident, and the spirocyclic carbons in
20a (diastereomers) appeared at d 82.2 and 82.4 compared to this
same carbon in 10a at d 68.8. The former observation indicated
that the azabicyclo[2.2.2]octane moiety had ruptured, whereas
the latter one suggested that a heteroatom and not a carbon atom
had bonded to the spirocyclic carbon. Further NMR spectroscopic
analysis (HMQC, HMBC, DEPT) provided evidence consistent with
the azetidine structures 20a and 20b; key HMBC correlations are
indicated.
–
PhMe2SiX
2,6-lut.
–
–
O
O
S+
S+
N
Ph
N
H
Ph
H
24
23
Scheme 5. Mechanistic speculation regarding the conversion of 19 into 20.
within the azabicyclo[2.2.2]octane to the transiently electrophilic
C(3) of the Pummerer intermediate (cf. 21?22 or 24?20), and
(2) b-elimination of the amine function to generate the product’s
enone (cf. 22?20 or 23?24). The sequence of these events is not
known. Circumstantial evidence tends to favor the pathway pro-
ceeding through initial Pummerer reaction via 21 and 22: (a) treat-
ment of 19a with aqueous HCl led to formation of a ketone product
with the azabicyclo[2.2.2]octane system intact, suggesting that
protonation of the nitrogen per se (cf. 23) is not sufficient to pro-
mote ring cleavage, and (b) a secondary amine intermediate like
24 might be expected to undergo N-triflation under the reaction
conditions, but that product was not detected. Nevertheless, the
The formation of 20 from 19 requires two distinct mechanistic
operations (Scheme 5): (1) addition of the nitrogen nucleophile

1916
K. S. Feldman, A. Y. Nuriye / Tetrahedron Letters 50 (2009) 1914–1916
intensity) 398.0 (100% M+H+); HRMS (ESI) m/z calcd for [C26H24NOS]+,
398.1597; found, 398.1579.
failure of the silyl enol ether nucleophile to out-compete the ter-
tiary amine (or secondary amine after b-elimination) eliminates
this chemistry from use in crassanine-type alkaloid synthesis. Curi-
ously, however, this C(3)-azetidine spirocyclic indolenine structure
is found in the core of members of the chartelline alkaloids.9
Compound 15: mp 107–108 °C; IR (thin film) 3350, 1732, 1148; 1H NMR
(300 MHz, CDCl3) d 7.89–7.86 (m, 2H), 7.67–7.61 (m, 1H), 7.56–7.51 (m, 2H),
3.86 (dt, J = 7.2, 1.7 Hz, 1H), 3.45 (s, 3H), 3.19–3.17 (m, 1H), 3.14 (d, J = 8.1 Hz,
1H), 3.00–2.91 (m, 2H), 2.48–2.25 (m, 2H), 2.00–1.80 (m, 2H), 1.65–1.58 (m,
1H); 13C NMR (75 MHz, CDCl3) d 172.9, 138.2, 133.8, 129.1, 128.6, 62.6, 52.3,
47.8 (two carbons), 45.0, 26.8, 24.8, 19.5; LRMS (ESI+) m/z (relative intensity)
310.1 (100% M+H+); HRMS (ESI) m/z calcd for [C15H20NO4S]+, 311.1109; found,
311.1113.
Acknowledgment
Compound 16: mp 107–108 °C; IR (thin film) 3203 cmꢀ1 1H NMR (300 MHz,
:
CDCl3) d 9.52 (s, 1H), 7.49–7.46 (m, 2H), 7.36 (d, J = 8.0 Hz, 1H), 7.24 (t,
J = 3.1 Hz, 3H), 7.12 (d, J = 8.3 Hz, 1H), 7.05–7.01 (m, 1H), 6.91 (t, J = 7.5 Hz, 1H),
3.47–3.38 (m, 1H), 3.34–3.15 (m, 3H); 13C NMR (75 MHz, CDCl3) d 143.6, 138.0,
133.5, 131.7, 129.9, 126.9, 125.6, 125.5, 121.0, 120.0, 118.8, 113.0, 32.3, 28.7;
LRMS (ESI+) m/z (relative intensity) 348.0 (100% M+H+); HRMS (ESI) m/z calcd
for [C16H15BrNOS]+, 348.0053; found, 348.0058.
Support from the National Science Foundation via CHE 0808983
and CHE 0131112 (X-Ray Crystallography facility) is gratefully
acknowledged.
Compound 17: mp 91–92 °C; IR (thin film) 3207, 1737; 1H NMR (300 MHz,
CDCl3, ꢁ1:1 mixture of diastereomers) d 9.41 (s, 1H), 9.40 (s, 1H), 7.92–7.91 (m,
2H), 7.89–7.88 (m, 2H), 7.66–7.57 (m, 8H), 7.54–7.50 (m, 4H), 7.44–7.41 (m,
6H), 7.30–7. 29 (m, 2H), 7.23–7.18 (m, 2H), 7.10–7.05 (m, 2H), 4.47 (dd, J = 8.4,
7.0 Hz, 2H), 3.40 (s, 3H), 3.34 (s, 3H), 3.26–3.23 (m, 2H), 3.15–3.07 (m, 4H),
3.00–2.92 (m, 4H), 2.81–2.60 (m, 4H), 2.55–2.48 (m, 2H), 2.43 (br s, 2H), 2.40–
2.30 (m, 2H), 2.07–1.87 (m, 2H), 1.82–1.66 (m, 2H), 1.62–1.48 (m, 2H); 13C
NMR (75 MHz, CDCl3) d 172.6, 172.5, 144.0, 143.9, 139.3, 138.0, 137.9, 134.0,
132.7, 132.6, 131.4 (two carbons), 129.8 (two carbons), 129.5, 128.9, 127.4,
127.3, 125.4, 125.3, 120.6, 120.4, 120.3 (two carbons), 120.1, 112.7, 62.4, 62.3,
57.0 (two carbons), 56.7 (two carbons), 55.0, 54.9, 52.6, 52.5, 46.5, 46.4, 27.4,
24.3, 22.2 (three carbons), 20.7 (two carbons); LRMS (ESI+) m/z (relative
intensity) 599.2 (100% M+Na+); HRMS (ESI) m/z calcd for [C31H33N2O5S2]+,
577.1876; found, 577.1831.
References and notes
1. (a) Feldman, K. S.; Vidulova, D. B. Org. Lett. 2004, 6, 1869–1871; (b) Feldman, K.
S.; Boneva, V. D. Tetrahedron Lett. 2004, 45, 5035–5037; (c) Feldman, K. S.;
Karatjas, A. G. Org. Lett. 2004, 6, 2849–2852; (d) Feldman, K. S.; Vidulova, D. B.;
Karatjas, A. G. J. Org. Chem. 2005, 70, 6429–6440.
2. Feldman, K. S. Tetrahedron 2006, 62, 5003–5034.
3. (a) Feldman, K. S.; Skoumbourdis, A. P. Org. Lett. 2005, 7, 929–931; (b) Feldman,
K. S.; Skoumbourdis, A. P.; Fodor, M. D. J. Org. Chem. 2007, 72, 8076–8086; (c)
Feldman, K. S.; Fodor, M. D. J. Am. Chem. Soc. 2008, 130, 14964–14965.
4. Cava, M. P.; Watanabe, Y.; Bessho, K.; Weisbach, J. A.; Douglas, B. J. Org. Chem.
1968, 33, 3350–3352.
5. (a) Ojima, I.; Kogure, T. Organometallics 1982, 1, 1390–1399; (b) Evans, D. A.; Fu,
G. C. J. Org. Chem. 1990, 55, 5680–5683.
Compound 18a: mp 96–97 °C; IR (thin film) 3212, 1660 cmꢀ1 1H NMR
;
6. Cambridge crysallographic data base access for 10b: CCDC 651553.
7. Sundberg, R. J.; Bloom, J. D. J. Org. Chem. 1981, 46, 4836–4842.
8. Buss, A. D.; Hirst, G. C.; Parsons, P. J. J. Chem. Soc., Chem. Commun. 1987, 1836–
1837.
9. (a) Chevolot, L.; Chevolot, A.-M.; Ghajhede, M.; Larsen, C.; Anthoni, U.;
Christophersen, C. J. Am. Chem. Soc. 1985, 107, 4542–4543; (b) Anthoni, U.;
Chevolot, L.; Larsen, C.; Neilsen, P. H.; Christophersen, C. J. Org. Chem. 1987, 52,
4709–4715.
(300 MHz, CDCl3, ꢁ1:1 mixture of diastereomers) d 9.12 (s, 1H), 9.02 (s, 1H),
7.68–7.64 (m, 4H), 7.60 (dd, J = 7.7, 3.4 Hz, 2H), 7.47–7.42 (m, 6H), 7.32–7.29
(m, 2H), 7.29–7. 26 (m, 2H), 7.22 (t, J = 14.9 Hz, 2H), 7.12–7.08 (m, 2H), 4.22 (s,
1H), 4.18 (s, 1H), 3.22–3.14 (m, 4H), 3.09–3.02 (m, 2H), 2.76–2.68 (m, 4H),
2.36–2.31 (m, 1H), 2.29 (s, 3H), 2.28 (s, 3H), 2.25–2.17 (m, 1H), 2.04 (br s, 4H),
1.67–1.59 (m, 2H), 1.26 (t, J = 7.2 Hz, 4H); 13C NMR (75 MHz, CDCl3) d 195.4,
195.3, 144.2, 144.1, 143.7, 143.6, 143.4, 137.6, 137.4, 132.5, 132.4, 130.9, 130.8,
129.3 (two carbons), 127.1, 126.9, 125.0 (two carbons), 124.9 (two carbons),
120.7, 120.3, 120.2 (two carbons), 120.1, 112.1, 59.0 (two carbons), 54.7, 54.6,
50.1, 49.5, 31.9, 31.8, 26.3, 26.0, 24.3 (two carbons), 23.5, 21.9, 21.7; LRMS
(ESI+) m/z (relative intensity) 419.1 (100% M+H+); HRMS (ESI) m/z calcd for
[C26H30N3O3S]+, 419.1781; found, 419.1793.
10. Spectral data for 7a, 8a, 8b, 9b, 10a, 10b, 15, 16, 17, 18a, 18b, 20a, and 20b.
Compound 7a: mp 70–71 °C: IR (thin film) 3338, 1668 cmꢀ1
;
1H NMR
(300 MHz, CDCl3) d 8.14 (s, 1H), 7.64–7.61 (m, 1H), 7.24–6.95 (m, 9H), 5.69
(t, J = 0.8 Hz, 1H), 5.58 (m, 1H), 2.87 (t, J = 7.4 Hz, 2H), 2.62 (t, J = 7.4 Hz, 2H),
1.94 (quintet, J = 7.4 Hz, 2H), 1.77 (dd, J = 0.6, 0.9 Hz, 3H); 13C NMR (75 MHz,
CDCl3) d 202.0, 144.2, 137.2, 137.0, 129.0, 127.6, 126.3, 125.6, 124.4, 123.4,
121.5, 119.6, 119.5, 111.0, 36.9, 24.9, 24.2, 17.5; LRMS (ESI+) m/z (relative
intensity) 336.1 (100% M+H+); HRMS (ESI) m/z calcd for [C21H22NOS]+,
336.1409; found, 336.1422.
Compound 18b: mp 64–65 °C; IR (thin film) 3230, 1637 cmꢀ1 1H NMR
;
(300 MHz, CDCl3) d 9.27 (s, 1H), 9.18 (s, 1H), 7.73–7.65 (m, 10H), 7.55–7.51 (m,
2H), 7.45–7.39 (m, 10H), 7.29–7.27 (m, 2H), 7.22 (t, J = 7.6 Hz, 2H), 7.10 (d,
J = 7.8 Hz, 2H), 7.06 (d, J = 7.7 Hz, 2H), 4.28 (s, 1H), 4.25 (s, 1H), 3.29–3.10 (m,
4H), 3.17–3.10 (m, 2H), 2.94–2.88 (m, 2H), 2.80–2.74 (m, 2H), 2.50–2.47 (m,
1H), 2.38–2.30 (m, 1H), 2.16–2.04 (m, 4H), 1.75–1.64 (m, 2H), 1.46–1.36 (m,
4H); 13C NMR (75 MHz, CDCl3) d 193.4, 193.3, 145.8 (two carbons), 143.7,
143.6, 142.9, 142.8, 137.7, 137.6, 137.4, 132.4, 132.2, 131.9 (two carbons),
130.7 (two carbons), 129.3 (two carbons), 129.2, 129.1, 128.1, 127.0, 126.8,
125.0, 124.9, 124.8, 120.7, 120.3, 120.2, 120.0, 112.2, 59.2 (two carbons), 55.0,
54.9, 52.0, 51.7, 31.8 (two carbons), 26.6, 26.3, 23.6, 21.9, 21.7; LRMS (ESI+) m/z
(relative intensity) 481.2 (100% M+H+); HRMS (ESI) m/z calcd for
[C30H29N2O2S]+, 481.1932; found, 481.1950.
Compound 8a: mp = 124–125 °C; IR (thin film) 3215, 1673 cmꢀ1 1H NMR
;
(300 MHz, CDCl3) d 9.95 (s, 1H), 7.68–7.64 (m, 3H), 7.43–7.38 (m, 3H), 7.34–
7.31 (m, 1H), 7.25–7.19 (m, 1H), 7.13–7.07 (m, 1H), 5.89 (br s, 1H), 5.73 (m,
1H), 3.12–2.99 (m, 2H), 2.86–2.77 (m, 2H), 2.09–2.02 (m, 2H), 1.88 (m, 3H); 13C
NMR (75 MHz, CDCl3) d 201.4, 144.3, 143.3, 137.8, 131.8, 130.9, 129.3, 126.8,
124.9, 124.8, 124.6, 121.8, 120.2, 120.0, 112.3, 36.7, 25.3, 23.7, 17.6; LRMS
(ESI+) m/z (relative intensity) 352.1 (100% M+H+); HRMS (ESI) m/z calcd for
[C21H22NO2S]+, 352.1369; found, 352.1371.
Compound 8b: mp 138–139 °C; IR (thin film) 3205, 1681, 1615 cmꢀ1 1H NMR
;
Compound 20a: IR (thin film) 1665, 1516 cmꢀ1 1H NMR (300 MHz, C6D6,
;
(300 MHz, CDCl3) d 10.0 (s, 1H), 7.70–7.61 (m, 3H), 7.43–7.30 (m, 9H), 7.23
(ddd, J = 7.0, 1.2, 1.1 Hz, 1H), 7.11 (ddd, J = 7.7, 1.0, 1.0 Hz, 1H), 6.09 (s, 1H), 5.89
(s, 1H), 3.17–3.00 (m, 2H), 2.88 (td, J = 6.9, 2.6 Hz, 2H), 2.20–2.03 (m, 2H); 13C
NMR (75 MHz, CDCl3) d 201.3, 149.1, 143.3, 137.8, 137.1, 131.8, 130.9, 129.3,
128.3, 128.1, 128.0, 126.8, 124.9, 124.8, 124.7, 121.5, 120.2, 120.0, 112.3, 38.7,
25.3, 23.6; LRMS (ESI) m/z (relative intensity) 414.2 (100% M+H+); HRMS (ESI)
m/z calcd for [C26H24NO2S]+, 413.1526; found 414.1528.
mixture of diastereomers) d 7.83–7.80 (m, 4H), 7.39–7.31 (m, 4H), 7.15–7.07
(m, 4H), 7.03–6.98 (m, 4H), 6.96–6.89 (m, 2H), 6.09 (br s, 2H), 3.50–3.36 (m,
2H), 3.24 (quit, J = 6.9 Hz, 2H), 2.74–2.67 (m, 4H), 2.46–2.36 (m, 2H), 2.27–
2.17 (m, 2H), 2.08–1.96 (m, 2H), 1.91 (s, 3H), 1.88 (s, 3H), 1.86–1.76 (m, 4H),
1.76–1.64 (m, 2H), 1.64–153 (m, 2H), 1.40–1.05 (m, 2H), 0.97–0.90 (m, 2H);
13C NMR (75 MHz, CDCl3) d 200.4 (two carbons), 185.9, 155.1 (two carbons),
142.1, 142.0, 140.0, 139.3, 138.8, 135.4 (two carbons), 130.4, 130.2 (two
carbons), 130.1, 129.9, 125.4, 125.3, 124.6, 124.5, 120.8 (two carbons), 82.4,
82.2, 59.5, 59.4, 52.5, 52.4, 32.5 (two carbons), 31.2 (two carbons), 29.0,
28.8, 27.0, 26.9, 26.7, 26.6, 26.5 (two carbons); LRMS (ESI+) m/z (relative
intensity) 403.1 (100% M+H+); HRMS (ESI) m/z calcd for [C25H27N2OS]+,
403.1847; found, 403.1844.
Compound 9a: IR (thin film) 3211, 1679 cmꢀ1 1H NMR (300 MHz, CDCl3) d
;
10.9 (br s, 1H), 7.68–7.43 (m, 6H), 7.23–7.00 (m, 5H), 6.9–6.82 (m, 3H), 2.93–
2.82 (m, 2H), 2.20–2.02 (m, 2H), 2.02–1.88 (m, 2H), 1.85 (s, 3H), 1.50 (s, 3H),
0.36–0.35 (app d, 6H); 13C NMR (75 MHz, CDCl3) d 145.0, 144.2, 138.7, 138.6,
133.7, 132.5, 130.7, 129.9, 129.4, 125.4, 125.0, 122.0, 120.5, 120.2, 113.1, 32.1,
29.0, 24.1, 18.8, 18.3, 0.690, ꢀ.072.
Compound 20b: IR (thin film) 1643, 1515 cmꢀ1 1H NMR (300 MHz, C6D6,
;
Compound 10a: IR (thin film) 1709, 1510 cmꢀ1 1H NMR (300 MHz, CDCl3) d
;
mixture of diastereomers) d 7.82–7.78 (m, 4H), 7.61–7.54 (m, 4H), 7.39 (d,
J = 7.2 Hz, 2H), 7.35 (d, J = 7.4 Hz, 2H), 7.11–7.00 (m, 14H), 6,96–6.90 (m,
2H), 6.18 (br s, 2H), 3.49–3.40 (m, 2H), 3.31–3.22 (m, 2H), 2.97–2.89 (m,
1H), 2.75–2.66 (m, 2H), 2.65–2.58 (m, 1H), 2.49 (dd, J = 12.2, 6.1 Hz, 1H),
2.42 (dd, J = 12.2, 6.6 Hz, 1H), 2.32–2.23 (m, 2H), 2.09–1.99 (m, 4H), 1.91–
1.58 (m, 6H), 1.36–1.27 (m, 2H), 1.04–0.92 (m, 2H); 13C NMR (75 MHz,
7.66–7.62 (m, 2H), 7.40–7.39 (m, 1H), 7.11–7.6.97 (m, 5H), 6.86 (dt, J = 7.6 Hz,
1H), 2.46–2.24 (m, 2H), 1.94–1.85 (m, 2H), 1.83–1.73 (m, 1H), 1.46–1.39 (m,
1H), 1.22 (s, 3H), 0.86 (s, 3H); 13C NMR (75 MHz, CDCl3) d 213.1, 182.5, 154.3,
140.9, 134.4, 129.3, 129.0, 128.2, 124.0, 123.5, 119.9, 68.8, 49.0, 36.7, 29.7, 21.8,
21.7, 21.2; LRMS (ESI+) m/z (relative intensity) 336.1 (100% M+H+); HRMS (ESI)
m/z calcd for [C21H22NOS]+, 336.1445; found, 336.1422.
CDCl3)
d 198.0 (two carbons), 184.7 (two carbons), 153.9, 143.9 (two
Compound 10b: mp 116–117 °C; IR (thin film) 1707, 1509 cmꢀ1 1H NMR
;
carbons), 138.7 (two carbons), 138.1, 137.9, 137.6, 137.3, 134.3, 134.2, 133.0,
131.2, 129.2, 129.1, 129.0 (three carbons), 128.7, 128.6, 127.9 (two carbons),
124.2 (two carbons), 123.4, 123.3, 119.7, 119.6, 81.2, 81.1, 58.3 (two
carbons), 51.3, 51.2, 31.5 (two carbons), 30.1, 30.0, 28.7, 28.5, 26.0, 25.7
(two carbons), 25.5; LRMS (ESI+) m/z (relative intensity) 465.2 (100% M+H+);
HRMS (ESI) m/z calcd for [C30H29N2OS]+, 465.2019; found, 465.2001.
(300 MHz, CDCl3) d 7.61–7.57 (m, 2H), 7.44–7.39 (m, 3H), 7.17–6.96 (m, 8H),
6.85 (d, J = 7.3 Hz, 1H), 3.17 (quintet, J = 9.0 Hz, 1H), 2.95–2.86 (m, 1H), 2.60–
2.37 (m, 3H), 2.04 (s, 3H), 1.89–1.78 (m, 1H); 13C NMR (75 MHz, CDCl3) d 210.2,
181.5, 154.1, 140.6, 137.5, 133.5, 129.3, 129.2, 128.8, 128.7, 128.2, 126.9, 126.7,
124.0, 123.6, 119.7, 68.6, 56.9, 37.0, 29.1, 21.7, 19.7; LRMS (ESI+) m/z (relative