3008
H. Saitoh et al. / Tetrahedron Letters 53 (2012) 3004–3008
in acetic acid14 gave a mixture of 32 and deacetal product 33 in
good total yield.
6. Baldwin, J. E. J. Chem. Soc., Chem. Commun. 1976, 734.
7. (a) Satoh, T.; Takano, K.; Ota, H.; Someya, H.; Matsuda, K.; Koyama, M.
Tetrahedron 1998, 54, 5557; (b) Satoh, T.; Kawashima, T.; Takahashi, S.; Sakai, K.
Tetrahedron 2003, 59, 9599.
In conclusion, we have developed a new procedure for a synthe-
8. Wakasugi, D.; Satoh, T. Tetrahedron 2005, 61, 1245.
sis of multi-substituted
a-chlorocyclobutanones from carbonyl
9. A solution of 15 (mixture of two diastereomers, 40.0 mg; 0.10 mmol) in toluene
(0.7 mL) was added dropwise to a solution of i-PrMgCl (2.0 mol/L solution in
THF; 0.15 mL; 0.3 mmol) in toluene (1.3 mL) at 0 °C, and the mixture was
stirred at 0 °C for 10 min. The reaction was quenched with satd aq NH4Cl
(1 mL), and the mixture was extracted with CHCl3 (3 ꢁ 3 mL). The organic layer
was dried over MgSO4 and concentrated in vacuo. The residue was purified by
column chromatography on silica gel using hexane/AcOEt as the eluent to give
3-chloro-1,1-dimethyl-8,11-dioxadispiro[3.2.4.2]tridecan-2-one 18 (22.2 mg;
85%) as colorless oil and 2-(8-chloromethyl-1,4-dioxaspiro[4.5]dec-8-yl)-2-
methylpropionitrile 19 (3.6 mg; 14%) as colorless crystals. Compound 18: IR
compounds by 4-Exo-Dig nucleophilic ring closure of magnesium
carbenoid intermediate to nitrile group as the key reaction in rela-
tively short steps. We believe that the chemistry presented in this
Letter contributes to the synthesis of various
a-chlorocyclobuta-
nones and also to the chemistry of magnesium carbenoids.
Acknowledgements
(neat) 2944, 2882, 1789 (CO), 1453, 1376, 1270, 1146, 1110, 1068, 1036 cmꢀ1
;
1H NMR (CDCl3) d 1.20 (s, 3H), 1.23 (s, 3H), 1.65–1.80 (m, 4H), 1.84–2.05 (m,
4H), 3.92–4.02 (m, 4H), 4.78 (s, 1H); MS (EI) m/z (%) 258 (M+, 1), 243 (1), 223
(10), 182 (10), 153 (39), 114 (81), 99 (97), 86 (63), 70 (100); HRMS (EI) calcd for
This work was supported by a Grant-in-Aid for Scientific
Research No. 22590021 from the Ministry of Education, Culture,
Sports, Science and Technology, Japan, and TUS Grant for Research
Promotion from Tokyo University of Science, which are gratefully
acknowledged.
C
13H19ClO3: 258.1023, found: 258.1029. Compound 19: mp 100.0–101.0 °C
(hexane); IR (KBr) 2961, 2230 (CN), 1454, 1375, 1153, 1126, 1113, 1034, 885,
738 cmꢀ1 1H NMR (CDCl3) d 1.46 (s, 6H), 1.51–1.98 (m, 8H), 3.77 (s, 2H), 3.93–
;
3.97 (m, 4H); MS (EI) m/z (%) 257 (M+, 0.3), 189 (9), 99 (100), 86 (11), 28 (24);
HRMS (EI) calcd for C13H20ClNO2: 257.1183, found: 257.1188.
Supplementary data
10. 1,3-CH insertion reaction of magnesium carbenoids giving cyclopropanes: (a)
Satoh, T.; Musashi, J.; Kondo, A. Tetrahedron Lett. 2005, 46, 599; (b) Satoh, T.;
Ogata, S.; Wakasugi, D. Tetrahedron Lett. 2006, 47, 7249; (c) Ogata, S.; Masaoka,
S.; Sakai, K.; Satoh, T. Tetrahedron Lett. 2007, 48, 5017; (d) Ogata, S.; Saitoh, H.;
Wakasugi, D.; Satoh, T. Tetrahedron 2008, 64, 5711; (e) Satoh, T.; Kuramoto, T.;
Ogata, S.; Watanabe, H.; Saitou, T.; Tadokoro, M. Tetrahedron: Asymmetry 2010,
21, 1; (f) Watanabe, H.; Ogata, S.; Satoh, T. Tetrahedron 2010, 66, 5675.
11. The magnesium carbenoids have two chiral carbon centers. The reaction of
magnesium carbenoids generated from 26A provided cyclobutanones, whereas
the reaction of those generated from 26B afforded significant amounts of
byproducts. The difference in reactivity indicates that these magnesium
carbenoids are diastereomers to each other. The relative configuration of
(3R⁄,4S⁄)-4-chloro-3-(naphthalen-1-yl)-4-((R⁄)-p-tolylsulfinyl)butanenitrile
(26cB0), which was prepared from E-25c and LiCH2CN, was determined by X-
ray molecular structure analysis (see Supplementary data). According to the
above experimental results and the relative configuration of 26cB0, the relative
configuration of adducts 26cA and 26cB was assigned to be 3R⁄,4R⁄ and 3R⁄,4S⁄,
respectively. In the case of magnesium carbenoids generated from 26B, an
anti-conformer, in which R group is located at opposite end of Cl, appears to be
the most stable conformational isomer (see Supplementary data). Therefore,
the side reactions such as 1,2-CC insertion and 1,3-CH insertion seem to take
place preferentially rather than the nucleophilic ring closure.
Supplementary data (X-ray crystallographic data of compound
26cB0 and schematic explanation of the reaction courses) associ-
ated with this article can be found, in the online version, at
References and notes
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