New synthesis of multi-substituted α-chlorocyclobutanones from 1-chloro-3-cyanoalkyl p-tolyl sulfoxides by 4-Exo-Dig nucleophilic ring closure of magnesium carbenoids to nitrile group as the key reaction

Article abstract of DOI:10.1016/j.tetlet.2012.03.127

1-Chloro-3-cyanoalkyl p-tolyl sulfoxides were easily prepared from 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from carbonyl compounds and chloromethyl p-tolyl sulfoxide, with lithium α-cyano carbanion of acetonitrile derivatives in good yields. Treatment of these sulfoxides with i-PrMgCl resulted in the formation of multi-substituted α- chlorocyclobutanones in good to high yields via the 4-Exo-Dig nucleophilic ring closure of the generated magnesium carbenoid intermediates to the nitrile group. This procedure provides a new and good way for the synthesis of multi-substituted α-chlorocyclobutanones from carbonyl compounds and substituted acetonitriles with formation of three carbon-carbon bonds in relatively short steps.

Full text of DOI:10.1016/j.tetlet.2012.03.127

Tetrahedron Letters 53 (2012) 3004–3008
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
New synthesis of multi-substituted
a-chlorocyclobutanones from
1-chloro-3-cyanoalkyl p-tolyl sulfoxides by 4-Exo-Dig nucleophilic ring
closure of magnesium carbenoids to nitrile group as the key reaction
⇑
Hideki Saitoh, Taro Sampei, Tsutomu Kimura, Yuichi Kato, Naoyuki Ishida, Tsuyoshi Satoh
Graduate School of Chemical Sciences and Technology, Tokyo University of Science, Ichigaya-funagawara-machi 12, Shinjuku-ku, Tokyo 162-0826, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
1-Chloro-3-cyanoalkyl p-tolyl sulfoxides were easily prepared from 1-chlorovinyl p-tolyl sulfoxides,
which were synthesized from carbonyl compounds and chloromethyl p-tolyl sulfoxide, with lithium
Received 17 February 2012
Revised 12 March 2012
Accepted 30 March 2012
Available online 4 April 2012
a
-cyano carbanion of acetonitrile derivatives in good yields. Treatment of these sulfoxides with i-PrMgCl
resulted in the formation of multi-substituted -chlorocyclobutanones in good to high yields via the
4-Exo-Dig nucleophilic ring closure of the generated magnesium carbenoid intermediates to the nitrile
group. This procedure provides a new and good way for the synthesis of multi-substituted -chlorocy-
a
a
Keywords:
Cyclobutanone
clobutanones from carbonyl compounds and substituted acetonitriles with formation of three carbon–
carbon bonds in relatively short steps.
a-Chlorocyclobutanone
Ó 2012 Elsevier Ltd. All rights reserved.
Magnesium carbenoid
4-Exo-Dig ring closure
Cyclization
Cyclopropanes and cyclobutanes, including cyclobutanones and
their derivatives, have been widely recognized to be versatile inter-
mediates in organic- and synthetic organic chemistry. The charac-
teristic reactivity of cyclopropanes and cyclobutanes is attributable
to their ring strain. A large number of studies for the chemistry,
synthesis, and synthetic uses of cyclopropanes have been carried
out; however, those for cyclobutanes and cyclobutanones are rela-
tively limited.1,2
The most widely used method for the synthesis of cyclobutanes
is intermolecular and intramolecular photochemical [2+2] cycload-
dition reactions of olefins.1 On the other hand, thermal [2+2] cyclo-
addition reactions of ketenes with olefins are widely used as the
general method for the synthesis of cyclobutanones.2,3 However,
in view of the importance of cyclobutanones in organic synthesis,
new methods for their synthesis are still very much desired.
We recently reported a new method for the synthesis of cyano-
cyclopropanes by the intramolecular alkylation of magnesium
carbenoids generated from 1-chloro-3-cyanoproyl p-tolyl sulfox-
ides with i-PrMgCl (Scheme 1).4 Thus, treatment of 1-chloro-3-
cyanopropyl p-tolyl sulfoxide 2, derived from 1-chlorovinyl p-tolyl
carbanion intermediate 4 generated from 3 by the excess
i-PrMgCl.4 Later, from the detailed inspection of this reaction, we
found that a trace amount of 2-chlorocyclobutanone 8 was gener-
ated as a byproduct. This product was presumed to be obtained
from the 4-Exo-Dig nucleophilic ring closure6 of magnesium carb-
enoid intermediate 3. It is interesting to note that 4-Exo-Dig ring
closure was reported to be a disfavored process.6
As described above, cyclobutanones are quite interesting and
important compounds in organic chemistry. We expected that if
the reaction is carried out with 1-chloro-3-cyanoalkyl p-tolyl
sulfoxides having no hydrogen on the carbon next to the cyano
group, a-chlorocyclobutanones would be produced via the 4-Exo-
Dig nucleophilic ring closure. In fact, this expectation was proved
to be fruitful. In this Letter, we describe a new and unprecedented
synthesis of multi-substituted
a-chlorocyclobutanones from
carbonyl compounds by 4-Exo-Dig nucleophilic ring closure of
magnesium carbenoid intermediates to nitrile group as the key
reaction, as shown in Scheme 2.
Thus, 1-chlorovinyl p-tolyl sulfoxides 10 were easily obtained
from carbonyl compounds 9 with chloromethyl p-tolyl sulfoxide.7
sulfoxide
1
with cyanomethyllithium, with excess i-PrMgCl
The reaction of 10 with lithium a-cyano carbanion of acetonitrile
resulted in the formation of cyanocyclopropane 6 in good yield
derivatives gave adducts, 1-chloro-3-cyanoalkyl p-tolyl sulfoxides
through magnesium carbenoid intermediate 3.5 This reaction was
11, in good to high yields.8 Finally, treatment of 11 with excess
proved to proceed via intramolecular SN2 reaction of
a
-cyano
i-PrMgCl resulted in the formation of multi-substituted a-chloro-
cyclobutanones 14 via the 4-Exo-Dig cyclization of the generated
magnesium carbenoid intermediates 12 and resultant imine anions
13.
⇑
Corresponding author.
E-mail address: tsatoh@rs.kagu.tus.ac.jp (T. Satoh).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.03.127

H. Saitoh et al. / Tetrahedron Letters 53 (2012) 3004–3008
3005
H
H
H
H
i-PrMgCl
(5 equiv)
CN
O
O
S(O)Tol
Cl
CN
O
O
LiCH2CN
O
O
THF
S(O)Tol
MgCl
Cl
Cl
3
1
2
H
MgCl
CN
CN
H
CN
O
O
O
O
O
H2O
O
MgCl
MgCl
Cl
4
6 (78%)
5
3
H
H
4-Exo-Dig
ring closure
H
H
H
H
O
N
H2O
O
O
O
O
NMgCl
O
O
MgCl
Cl
8 (trace)
Cl
Cl
7
3
Scheme 1. Two pathways for the reaction of magnesium carbenoid 3 giving cyanocyclopropane 6 and 2-chlorocyclobutanone 8 by the intramolecular SN2 reaction and 4-Exo-
Dig nucleophilic ring closure, respectively.
R3
R4
CN
TolS(O)CH2Cl
R1
R2
R1
R2
S(O)Tol
Cl
R1
R2
R3R4CHCN, LDA
O
S(O)Tol
2 or 3 steps
Lit. 7
THF, -78 °C
R3, R4 = H or Alkyl
Cl
9
10
11
R1, R2 = H, Alkyl, Aryl
R3
4-Exo-Dig
ring closure
R3
R4
R4
C
R3
R1
R2
R4
R1
H2O R1
R2
i-PrMgCl
N
O
NMgCl
R2
Toluene
MgCl
Cl
14
Cl
Cl
13
12
Scheme 2. General scheme for this work.
was obtained in 60% yield with chloroalkane 19 (33% yield). The
mechanism of this reaction is presumed to be as follows. The treat-
ment of 15 with i-PrMgCl resulted in the formation of magnesium
carbenoid 16 by the sulfoxide–magnesium exchange reaction.5 As
magnesium carbenoids have both nucleophilic and electrophilic
properties,7a 4-Exo-Dig nucleophilic ring closure must take place
to give imine anion intermediate 17, which was hydrolyzed in
the work up process to give 18. Chloroalkane 19 is the protonated
product of magnesium carbenoid intermediate 16.
Synthesis of 4-chloro-2,2,3,3-tetrasubstituted and 2-chloro-
3,3,4-trisubstituted cyclobutanones
Details of this procedure are reported using 1-chloro-3-cya-
noalkyl p-tolyl sulfoxide bearing two methyl groups at the a-posi-
tion of the cyano group 15 as a representative example for the
precursor of magnesium carbenoid intermediates (Scheme 3).
Thus, treatment of 1-chlorovinyl p-tolyl sulfoxide 17 with lithium
a-cyano carbanion of isobutyronitrile gave adduct 15 as a mixture
As we recognized that this will become a new and unprece-
of two diastereomers in 90% yield. A mixture of this adduct was
dented procedure for the synthesis of
we investigated the conditions for reducing the yield of protonated
a-chlorocyclobutanones,
treated with 5 equiv of i-PrMgCl (ether solution) in THF at 0 °C
for 30 min. Gratifyingly, the desired
a-chlorocyclobutanone 18
H3C CH3
S(O)Tol
Cl
O
O
(CH3)2CHCN (5 equiv), LDA
THF, -78 °C, 10 min, 90%
i-PrMgCl (5 equiv)
CN
O
O
THF, 0 °C, 30 min
S(O)Tol
Cl
1
15
(a mixture of two diastereomers)
H3C CH3
H3C CH3
4-Exo-Dig
ring closure
H3C CH3
NMgCl
H3C CH3
CN
CN
O
O
H2O
O
O
O
O
+
O
CH2Cl
MgCl
Cl
Cl
Cl
17
16
19 (33%)
18 (60%)
Scheme 3. Addition reaction of lithium
substituted -chlorocyclobutanone 18.
a-cyano carbanion of isobutyronitrile to 1-chlorovinyl p-tolyl sulfoxide 1 and the treatment of adduct 15 with i-PrMgCl to give multi-
a

3006
H. Saitoh et al. / Tetrahedron Letters 53 (2012) 3004–3008
Table 1
Investigation of the conditions for preparation of
a
-chlorocyclobutanone 18 from 15 with i-PrMgCl
H3C CH3
CN
H3C CH3
CN
H3C CH3
i-PrMgCl
O
O
O
O
O
O
O
+
CH2Cl
Conditions
S(O)Tol
Cl
Cl
15
19
18
Entry
Conditions
18
19
Temp (°C)
Time (min)
Solvent
Reagent (equiv)
Yield (%)
Yield (%)
1
2
3
4
5
6
7
8
9
0
30
60
10
60
10
10
10
10
10
THF
THF
THF
THF
Toluene
Toluene
Toluene
Toluene
Toluene
i-PrMgCl in Et2O (5)
i-PrMgCl in Et2O (5)
i-PrMgCl in Et2O (5)
i-PrMgCl in Et2O (5)
i-PrMgCl in THF (5)
i-PrMgCl in THF (5)
i-PrMgBr in THF (5)
i-PrMgCl in THF (3)
i-PrMgCl in THF (2)
60
40
59
55
69
84
80
85
33
59
31
30
6
12
11
14
13
ꢀ78 to 0
0
0
0
0
0
0
0
a
34
a
Starting material 15 was recovered in 50% yield.
R3CH2CN (5 equiv),
LDA
Table 2
H
R3
Synthesis of 4-chloro-2,2,3,3-tetrasubstituted cyclobutanones 22 from
nitrile adducts 21
1
through
CN
O
O
i-PrMgCl (3 equiv)
1
S(O)Tol
THF, -78 °C, 10 min
Toluene, 0 °C, 10 min
Cl
R3
23
R3 R3
CN
R3
R3
R3
O
CN
20
i-PrMgCl
(3 equiv)
H
R3
O
O
O
O
O
O
24a R3 = CH3 (54%)
O
1
24b R3 = CH3CH2 (42%)
24c R3 = PhCH2CH2 (46%)
LDA
Toluene,
0 °C, 10 min
S(O)Tol
Cl
Cl
Cl
24
21
22
Entry
Nitrile 20
21/Yield (%)
21a (99)
22/Yield (%)
Scheme 4. Synthesis of 2-chloro-3,3,4-trisubstituted cyclobutanones 24 from
nitrile adducts 23 derived from 1 and acetonitrile derivatives.
O
O
O
CN
1
2
(82)
(88)
3 equiv of i-PrMgCl (in THF solution) in toluene at 0 °C for 10 min
was found to be the condition of choice for this reaction (entry 8)
and we used these conditions throughout in this study.9
The procedure starting with 1-chlorovinyl p-tolyl sulfoxide 1
described above was carried out with cyclopropanecarbonitrile,
cyclopentanecarbonitrile, cyclohexanecarbonitrile, 3-cyanopen-
tane, and 3-cyano-1,5-diphenylpentane and the results are sum-
marized in Table 2. As shown in Table 2, addition reactions of
O
Cl
22a
O
CN
21b (85)
21c (94)
O
Cl
22b
lithium
a-cyano carbanions to 1 afforded good to quantitative
O
3
4
(76)
(74)
CN
yields of adducts 21 as single isomers. The treatment of cyclic
nitrile adducts 21a–21c with i-PrMgCl under the conditions
described above gave structurally very interesting dispiro-
O
O
O
Cl
Cl
22c
compounds,
10-chlorodispiro[2.0.5.2]undecan-11-one
22a,
O
O
12-chlorodispiro[4.0.5.2]tridecane-13-one 22b, and 14-chlorodi-
spiro[5.0.5.2]tetradecan-13-one 22c in good to high yields (entries
1–3). The reactions with acyclic nitriles also gave adducts 21d and
21e in 99% and 67% yields, respectively. The key reaction of 21d
and 21e with i-PrMgCl afforded 1,1-disubstituted 3-chlorospi-
ro[3.5]nonan-2-ones 22d and 22e in somewhat lower yields
compared with those of 22a–c. These results implied that the
procedure described above has general applicability.
CN
21d (99)
21e (67)
22d
Ph
Ph
O
Ph
O
5
(62)
CN
O
Next, we investigated this procedure with mono-substituted
acetonitriles (Scheme 4). Thus, the addition reaction of 1 with ex-
Cl
Ph
22e
cess lithium a
-cyano carbanion of propionitrile (R3 = CH3), butyro-
nitrile (R3 = CH3CH2), and 4-phenylbutyronitrile (R3 = PhCH2CH2)
gave adducts 23 as a mixture of diastereomers in quantitative
yields. Treatment of adducts 23 with i-PrMgCl in toluene gave
the desired 2-chlorocyclobutanones 24a to 24c in up to 54% yield.
The cyanocyclopropanes, which were worried about to be pro-
duced by the intramolecular SN2 reaction as described in the intro-
duction, were not observed. The reason why the yields of 24 were
chloroalkane 19 and the results are summarized in Table 1. Entry 1
shows the result described above. As shown in entries 2–4, when
the reaction was conducted in THF, a significant amount of 19
was obtained. Using toluene and i-PrMgCl in ether for 10 min
was found to be much better condition (entry 5). When i-PrMgCl
or i-PrMgBr in THF solution was used in this reaction, the desired
18 was obtained in up to 84% yield (entries 6 and 7). Finally, using

H. Saitoh et al. / Tetrahedron Letters 53 (2012) 3004–3008
3007
Table 3
Synthesis of 4-chloro-2,2,3-trisubstituted cyclobutanones 27 from aldehydes
(CH3)2CHCN (5 equiv),
LDA
i-PrMgCl
(3 equiv)
H3C CH3
H3C
R
CH3
R
H
S(O)Tol
Cl
R
CN
RCHO
O
H
Toluene,
0 °C, 10 min
H
S(O)Tol
THF, -78 °C
Cl
27
Cl
25
26
Entry
Aldehyde
R
25
26/Yield (%)
27/Yield (%)
1
2
PhCH2CH2
PhCH2CH2
Z-25a
E-25a
26aA (95)
26aB (96)
27a (51)a
H3C
H
CH3
27a (32)b,c
Ph
O
Cl
3
4
Ph
Ph
Z-25b
E-25b
26bA (95)
26bB (81)
H3C
Ph
27b (59)a
CH3
27b (trace)d
O
H
Cl
H3C
CH3
5
6
Z-25c
E-25c
26cA (74)
26cB (80)
27c (44)a
1-Naph
O
H
Cl
27c (trace)e
a
b
c
Single isomer (configuration not determined).
About 1:1 mixture of two diastereomers.
Cyclopropane 28 (1,3-CH insertion product of the magnesium carbenoid intermediate) was obtained in 39% yield.
Olefin 29 (1,2-CC insertion product of the magnesium carbenoid intermediate) was obtained in 74% yield.
Olefin 30 (1,2-CC insertion product of the magnesium carbenoid intermediate) was obtained in 34% yield.
d
e
CN
CH3
H
Ph
H
1-Naph
Ph
CN
CN
H
H
H3C
H3C
H3C
CH3
CH3
28
29
somewhat low is due to the formation of about 15% of protonated
chloroalkanes and some structurally unknown byproducts.
26bB and 26cB gave olefins 29 and 30 as major products with trace
amount of the desired products (entries 4 and 6). Olefins 29 and 30
are the 1,2-CC insertion products (aryl group migration product) of
the magnesium carbenoid intermediates. The mechanism of this
stereospecificity of the reactions is unclear at present.11,12
Synthesis of 4-chloro-2,2,3-trisubstituted cyclobutanones from
aldehydes
a
-Chlorocyclobutanones are quite interesting intermediates in
organic synthesis. Two known reactions of the -chlorocyclobuta-
none were applied to 18 (Scheme 5). Thus, treatment of 18 with so-
dium methoxide in methanol gave cyclopropane bearing
a
Finally, the procedure was carried out starting from aldehydes
(Table 3). Thus, 1-chlorovinyl p-tolyl sulfoxides 25 were synthesized
from 3-phenylpropanal, benzaldehyde, and 1-naphthaldehyde in
two steps as a mixture of easily separable two geometrical isomers.
a
methoxycarbonyl group 31 in 85% yield via the quasi Favorskii
rearrangement.13 Reduction of the chlorine atom of 18 with zinc
Additionreaction of lithium a-cyano carbanionofisobutyronitrileto
25 gave high yields of adducts 26.
Treatment of 26aA, derived from Z-25a, with i-PrMgCl resulted in
the formation of the desired 4-chloro-2,2-dimethyl-3-(2-phenyl-
ethyl)cyclobutanone 27a in 51% yield as a single isomer (entry 1).
Interestingly, the reaction of adduct 26aB, derived from E-25a, gave
27a as about 1:1 mixture of two diastereomers with a significant
amount of cyclopropane 28, derived via the 1,3-CH insertion of mag-
nesium carbenoid intermediate.10 Entries 3–6 show the results ob-
tained from adducts 26 derived from aromatic aldehydes.
Interestingly, the reaction of the adducts 26bA and 26cA (derived
from Z-25b and Z-25c, respectively) gave the desired 3-aryl-4-
chloro-2,2-dimethylcyclobutanones 27b and 27c in moderate yields
as both single isomers (entries 3 and 5). However, the reaction of
H3C
H3C CH3
CH3
NaOCH3
O
O
O
O
O
CH3OH, r.t.,
overnight, 85%
COOCH3
Cl
31
18
H3C CH3
H3C CH3
Zn
O
O
18
O
+
O
O
AcOH, 50 °C,
overnight
32 (25%)
33 (63%)
Scheme 5. Two reactions of
a
-chlorocyclobutanone 18.

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
http://dx.doi.org/10.1016/j.tetlet.2012.03.127.
References and notes
1. For reviews on the chemistry, synthesis, and synthetic uses of cyclobutanes: (a)
Demuth, M.; Mikhail, G. Synthesis 1989, 145; (b) Inoue, Y. Chem. Rev. 1992, 92,
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