C O M M U N I C A T I O N S
Table 2. Alkylation of the Allyl Sulfones 15-17
Scheme 3
substrate
R I
b
conditions
yield (%)c
15EE
EtI
EtIb
EtI
EtI
EtI
14
1.1 equiv of K or NaHMDS,
10% HMPA, 3 h
2.5 equiv of K or NaHMDS,
18ET, 88, 95
16EE
19ET, 24, 70
19ET, 50
20% HMPA, 4 h
16EE
2.5 equiv of KHMDS,
2.55 equiv of 18-c-6, 4 h
2.5 equiv of NaHMDS,
2.55 equiv of 15-c-5, 4 h
2.5 equiv of NaHMDS,
2.55 equiv of 18-c-6, 4 h
1.5 equiv of NaHMDS,
15% HMPA, 14, 3 h
1.2 equiv of KHMDS,
1.3 equiv of 18-c-6, 3 h
1.2 equiv of NaHMDS,
1.25 equiv of 15-c-5, 3 h
1.5 equiv of NaHMDS,
1.55 equiv of 18-c-6, 2 h
16EE
19ET, 20
for 2-ethylated 1,3-dienes. The studies indicate that the reaction
with catalyst CoCl2[(R,R)DIOP] and MeMgCl selectively gives the
3-ethyl 1,3-EZ-diene with a 9.3/1 ratio of Et-8EZ/EE in 87% yield
(Table 3, entry 10).
Therefore, the desulfonylation of 21ET gives the four different
dienes with good to excellent selectivity (Scheme 3, Table 3).
Mechanistic definition and further optimization of the ligand-
mediated process require further study, but the synthetic potential
of this process is highly apparent.
16EEa
19ET, 99
17EE/EZ
17EE/EZ
17EE/EZ
17EE/EZ
21ETrâ, 71
21ETrâ, 30
21ETrâ, <5
21ETrâ, 85
14
14
14
In conclusion, a new three-operation conjunctive strategy is
available for the synthesis of EE, EZ, and ET dienes (Scheme 1).
This protocol employs a sequential Wadsworth-Emmons reaction
using GAPPS reagent 5/12 followed by alkylation of an allylic
sulfone anion, and finally ligand-mediated, palladium-catalyzed
reductive or alkylative desulfonylation.
a Repeating this reaction with i-butyl iodide, i-propyl iodide, and iodide
14 provided the analogous ET-alkylation products in 82, 73, and 64% yield,
respectively. b 1.1 equiv of EtI was used. c 1:1 mixture of diastereomers.
Table 3. Conversion of Allylic Sulfones to 1,3-Dienesa
entry
21ET
conditions
ratio, yield (%)
Acknowledgment. We are highly grateful to Professor Gais for
his insights and extensive discussion of the mismatched crown ether
effect in the alkylations of the R-sulfonyl carbanions.
Rc ) H
8EE/EZ/ET
4.6/1/-, 72
2.5/1/-, 52
4.2/1/-, 60
3.7/1/-, 85
1/7.7/-, 84
1/6.4/-, 89
6.5/15.0/1, 87
13.2/-/1, 90
1
2
3
4
5
6
7
8
r
2.5% Pd, 7.5% (R,R)DIOP,b 5 h
2.5% Pd, 7.5% (R,R)DIOP,b 5 h
2.5% Pd, 7.5% (S,S)DIOP,b 5 h
2.5% Pd, 7.5% (S,S)DIOP,b 5 h
PdCl2[(S,S)-Trost],b,c 10 h
PdCl2[(R,R)-Trost],b,c 10 h
PdCl2[(D,L)-Trost],b,c 10 h
2.5% Pd, 15%(1-pyrrolidinyl)3P,
20 min
â
Supporting Information Available: Additional experiments, dis-
cussion, experimental procedures, and 1H, 13C spectra (PDF). This
r
â
r
â
râ
râ
References
(1) Dias, L. C.; Meira, P. R. R. Tetrahedron Lett. 2002, 43, 185-187. Kalesse,
M.; Quitschalle, M.; Khandavalli, C. P.; Saeed, A. Org. Lett. 2001, 3,
3107-3109. Smith, A. B., III; Brandt, B. M. Org. Lett. 2001, 3, 1685-
1688.
(2) Roush, W. R.; Dilley, G. J. Tetrahedron Lett. 1999, 40, 4955-4959.
(3) Nicolaou, K. C.; Li, Y.; Weyershausen, B.; Wei, H.-X. Chem. Commun.
2000, 307-308 and references therein.
9
râ
râ
5% Pd[(t-Bu)3P]2, 4 h, 45 °C
-/-/1, 90
Rc ) Me
Et-8EZ/EE
9.3/1, 87
10
5% CoCl2[(R,R)-DIOP], 3 × 1.5
equiv of MeMgCl,d 4 h
(4) Kabayshi, J.; Kubota, T.; Tsuda, M. J. Org. Chem. 2002, 67, 1651-1656.
(5) Trost, B. M.; Schmuff, N. R. J. Am. Chem. Soc. 1985, 107, 396-405.
Breulles, P.; Uguen, D. Tetrahedron Lett. 1987, 28, 6053-6056. Ghera,
E.; Yechezkel, T.; Hassner, A. J. Org. Chem. 1996, 61, 4959-4966. Trost,
B. M.; Arndt, H. C.; Strege, P. E.; Verhoeven, T. R. Tetrahedron Lett.
1976, 4, 3477-3478.
a Unless specified, the reaction was done in THF at 0 °C, and super
hydride (S-H) was used as the hydride source. b 5% LiCl was added.
c Preformed catalyst was used. d MeMgCl was added portionwise in 2 h
and stirred for 2 h. See Supporting Information for expanded tables.
(6) Gais, H.-J.; van Gumpel, M.; Schleusner, M.; Raabe, J.; Runsink, J.;
Vermeeren, C. Eur. J. Org. Chem. 2001, 4275-4303. Gais, H.-J.; van
Gumpel, M.; Raabe, G.; Muller, J.; Braun, S.; Lindner, H. J.; Rohs, S.;
Runsink, J. Eur. J. Org. Chem. 1999, 1627-1651 and references therein.
(7) Kotake, H.; Yamamoto, T.; Kinoshita, H. Chem. Lett. 1982, 82, 1331-
1334. Mohri, M.; Kinoshita, H.; Inomata, K.; Kotake, H.; Takagaki, H.;
Yamazaki, K. Chem. Lett. 1986, 1177-1180. J. Synlett 1993, 113-114.
(8) Tsuji, J.; Minami, I.; Shimizu, I. Synthesis 1986, 623-627.
strong σ-donating character, exclusively delivers the terminal diene
8ET in 90% yield (entry 9). The ligand screening study also
illustrates that ligands with a strong σ-donating character provide
high yields and rapid reactions.
Preliminary studies with methylation reagents show that the
diastereomeric mixture 21ETrâ is also an appropriate precursor
JA0377596
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