Reactions of the carbanion of chloromethyl methyl sulfone with aldehydes and ketones

Article abstract of DOI:10.1016/S0040-4039(02)02825-3

Addition of the carbanion of chloromethyl methyl sulfone to aldehydes and ketones proceeds faster than its degradation via the Ramberg-Baecklund reaction. Chlorohydrins and oxiranes produced from aldehydes treated with an excess of base undergo the Ramber

Full text of DOI:10.1016/S0040-4039(02)02825-3

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 1473–1475
Reactions of the carbanion of chloromethyl methyl sulfone with
aldehydes and ketones
Mieczysław Ma˛kosza,* Natalia Urban´ska and Alexey A. Chesnokov
Institute of Organic Chemistry, Polish Academy of Sciences, ul. Kasprzaka 44, 01-224 Warszawa 42, POB 58, Poland
Received 21 October 2002; revised 2 December 2002; accepted 13 December 2002
Abstract—Addition of the carbanion of chloromethyl methyl sulfone to aldehydes and ketones proceeds faster than its
degradation via the Ramberg–Baecklund reaction. Chlorohydrins and oxiranes produced from aldehydes treated with an excess
of base undergo the Ramberg–Baecklund reaction giving allylic alcohols, whereas the reaction of ketones gives the oxiranes.
© 2003 Elsevier Science Ltd. All rights reserved.
Carbanions of chloromethyl sulfones are versatile reac-
tants of great value in organic synthesis widely used for
synthesis of oxiranes,1–3 vicarious nucleophilic substitu-
tion of hydrogen,4,5 etc. However only aryl or t-butyl
chloromethyl sulfones can be used as the carbanion
precursors since alkyl chloromethyl sulfones treated
with strong bases undergo rapid Ramberg–Baecklund
(R–B) reaction.6,7 A literature search revealed that there
is one example of an intermolecular reaction of the
carbanion of chloromethyl methyl sulfone 1, the sim-
plest representative of such sulfones. It’s reaction with
cyclohexanone gave the corresponding chlorohydrin
and oxirane.3
followed by the Ramberg–Baecklund reaction should
give an allylic alcohol.
Initial experiments in which benzaldehyde and
chloromethyl methyl sulfone 1 were reacted in the
presence of concentrated aqueous NaOH and tetra-
butylammonium chloride, under PTC conditions,8 gave
negative results, although these conditions were used
efficiently for the Darzens condensation of
chloromethyl aryl sulfones.2,8 On the other hand when
these reactants were treated with t-BuOK in THF at
low temperature (−78°C) the expected chlorohydrin was
produced in high yield. When the reaction mixture was
quenched with aqueous NH4Cl at −78°C the chlorohy-
drin 2a was isolated as a mixture of two diastereoiso-
mers (syn:anti:70:30 on the basis of NMR spectra
On the other hand reactions of such carbanions could
offer interesting possibilities in organic synthesis, for
example addition of the carbanion of 1 to an aldehyde
3
namely the magnitudes of the coupling constants JHH
Scheme 1.
Keywords: allylic alcohols; carbanions; chloromethyl methyl sulfone; Ramberg–Baecklund reaction.
* Corresponding author. Tel.: +48 22 6318788, fax: +48 22 6326681; e-mail: icho-s@icho.edu.pl
0040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02825-3

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M. Ma˛kosza et al. / Tetrahedron Letters 44 (2003) 1473–1475
for the HCCl and HCOH protons), but when the mix-
ture was warmed to 0°C before quenching, intramolec-
ular substitution took place to give the expected
methylsulfonyl oxirane 3a (trans:cis >98:2) on the basis
methylsulfonyl carbanion. The latter process is sup-
ported experimentally because the oxirane 3a, when
separately prepared, does undergo the intramolecular
reaction producing the allylic alcohol when treated with
an excess of base. The R–B reaction proceeding via
epoxide ring opening to give allylic alcohols has been
reported earlier.9
3
of NMR spectra-coupling constant values JHH for the
HCHPh and HCSO2CH3 protons) (Scheme 1).
Thus avoiding an excess of base and working at low
temperature it was possible to execute a typical car-
boanionic reaction of the carbanion of chloromethyl
methyl sulfone: addition to the carbonyl group produc-
ing chlorohydrin 2 and subsequently the formation of
oxirane 3 which proceeded much faster than the R–B
reaction. It should be stressed that the carbanion of 1 is
relatively stable at −78°C. When 1 was treated at −78°C
with t-BuOK, and benzaldehyde added after 5 s and
the mixture quenched, 2a was obtained in 96% yield.
Further conversion of the chlorohydrin or the oxirane
via the R–B reaction proceeds when they are treated
with an excess of strong base: t-BuOK. Thus direct
treatment of a mixture of benzaldehyde and 1 with
t-BuOK (3 equiv.) at −78°C and subsequently warming
the mixture to 0°C gave 1-phenylallyl alcohol 4a. The
same alcohol was obtained upon treatment of the iso-
lated chlorohydrin 2a or oxirane 3a with 2 equiv. of
t-BuOK. Other aromatic aldehydes: o-chloro- and p-
methoxybenzaldehyde and also aliphatic aldehydes, e.g.
isobutyraldehyde react with 1 in a similar way to give
the corresponding allylic alcohols 4b–d (Scheme 2). In
the latter cases the reaction was carried out in the
presence of a threefold excess of t-BuOK at −78“0°C
as a one-pot procedure, the corresponding allylic alco-
hols being obtained as the only products.
In order to clarify whether conversion of the chlorohy-
drin 2a to the alcohol 4a proceeds via the intermediate
oxirane 3a, chlorohydrin 2a (a mixture of syn and anti)
was treated with 3 equiv. of t-BuOK at −50°C. Quench-
ing the mixture after 5 min gave 4a (40%), unreacted 2a
(45%) and oxirane 3a (15%). In a separate experiment it
was shown that under such conditions the oxirane 3a is
converted into 4a to a much lower degree (20%), the
majority of the oxirane (80%) being recovered. Thus in
the presence of an excess of base, 2a is converted
directly into 4a much faster than the conversion of
2a“3a and then 3a“4a.
A facile one-pot synthesis of allylic alcohols in the base
promoted reaction of 1 with aldehydes indicates that
addition of the carbanion of 1 to aldehydes proceeds
faster than the competing R–B reaction and that this
carbanion can be considered as a synthetic equivalent
of a vinyl carbanion.10,11
The carbanion of 1 can also be trapped efficiently by
aliphatic ketones, the corresponding oxiranes being the
final products. These reactions were conducted as
described for the synthesis of chlorohydrin 2a.11 Stan-
dard workup gave analytically pure compounds 5a,b12
(Scheme 3).
The allylic alcohols can be produced in the reactions of
aldehydes with 1 via the R–B reaction in two ways
(Scheme 2).
Contrary to the observations reported earlier,3 where
lithium bases were used, in this case the reaction cannot
be stopped at the chlorohydrin stage because further
cyclization of its potassium salts to oxiranes is a very
fast process. These oxiranes do not enter the R–B
reaction under these conditions as do the oxiranes
produced from aldehydes. We have not observed for-
mation of allylic alcohols when these oxiranes were
treated with an excess of t-BuOK even at room
temperature.
The intermediate chlorohydrin 2a on treatment with an
excess of base can undergo direct intramolecular substi-
tution of the halogen with the methylsulfonyl carbanion
to form a substituted episulfone and subsequently the
allylic alcohol 4a. Alternatively cyclization of the
chlorohydrin anion may give the oxirane 3a, which
undergoes intramolecular epoxide ring opening with the
Scheme 2.

M. Ma˛kosza et al. / Tetrahedron Letters 44 (2003) 1473–1475
1475
Scheme 3.
References
CHSO2CH); 3.1 (s, 3H, CH3). 13C NMR: l 132.3; 129.6;
128.7; 126.0; 69.7; 56.8; 38.9. MS (EI 70 eV); m/z (5) 198
(1.9); 119 (34); 91 (100); 65 (19.5). Calcd for C9H10SO3:
C, 54.54; H, 5.09; S, 16.14. Found: C, 54.39; H, 5.16; S,
16.00%. When t-BuOK was used in threefold excess (0.7
g) and the mixture warmed to 0°C before quenching, the
standard workup (Et2O (3×5 ml), Na2SO4) gave 1-phenyl-
allyl alcohol 4a (0.17 g, 63%): 1H NMR: l 7.3–7.5 (m,
5H, Ph), 6.1 (m, 1H, CHꢀCH2), 5.4 (:dt, J1=17.1 Hz,
J2:1.6 Hz, 1H, CH(OH)), 5.2 (m, 2H, CHꢀCH2), 2.2
(br. s, 1H, OH). 13C NMR: l 142.5; 140.1; 128.4; 127.6;
126.2; 114.9; 75.2. Data for the other allylic alcohols
obtained in the reaction of 1 with o-chlorobenzaldehyde,
p-methoxybenzaldehyde and isobutyraldehyde (Scheme
1. Simpkins, N. S. Sulphones in Organic Synthesis; Perga-
mon Press: Oxford, 1993.
2. (a) Jon´czyk, A.; Ban´ko, K.; Makosza, M. J. Org. Chem.
1974, 40, 266; (b) Hewkin, C. T.; Jackson, R. F. W.
Tetrahedron Lett. 1990, 31, 1877.
3. Durst, T.; Tin, K.-Ch.; Reinach-Hirtzbach, F.; Decesare,
J. M.; Ryan, M. D. Can. J. Chem. 1979, 57, 258.
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272; (b) Ma˛kosza, M.; Wojciechowski, K. Liebigs Ann/
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5. Ma˛kosza, M.; Kwast, A. J. Phys. Org. Chem. 1998, 11,
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6. Ramberg, L.; Baecklund, B. Ark. Kem. Mineral. Geol.
1940, 13A N.27; Chem. Abstr. 1940, 34, 4725.
7. Paquette, L. A. Org. React. 1977, 25, 1.
8. (a) Ma˛kosza, M.; Fedoryn´ski, M. Adv. Catal. 1987, 35,
375; (b) Dehmlov, E.; Dehmlov, S. Phase Transfer Catal-
ysis; 3rd ed.; VCH, 1993.
9. Evans, P.; Taylor, R. J. K. Tetrahedron Lett. 1997, 38,
3055.
10. Potassium t-butoxide (0.27 g, 2.4 mmol. 1.2 equiv.) was
added to a cooled (−78°C) solution of 1 (0.26 g, 2 mmol)
and benzaldehyde (0.21 g, 2 mmol) in dry THF (2 ml).
The mixture was stirred for 30 min at −78°C and
quenched with an excess of aqueous NH4Cl. Standard
work-up (EtOAc (3×5 ml), Na2SO4) gave pure chlorohy-
drin 2a (0.46 g, 98%) as a mixture of two diastereoiso-
mers (syn:anti=68:32). Double recrystallization from
CH2Cl2/pentane gave a single diastereoisomer syn-2a: mp
142–143°C (racemic mixture). 1H NMR (200 MHz,
CDCl3): l 7.3–7.5 (m, 5H, Ph), 5.8 (d, J=1.3 Hz, 1H,
CH(OH)); 4.7 (d, J=1.3 Hz, 1H, CH(SO2CH3)); 3.2 (s,
3H, CH3); 1.7 (br.s, 1H, OH). 13C NMR (50 MHz,
CDCl3): l 138.0; 128.8; 128.7; 126.0; 78.1; 70.3; 38.7. MS
(EI 70 eV): m/z (%) 236 (0.9); 234 (2.5); 156 (1.9); 154
(5.9); 107 (100); 91 (17.2); 79 (37.9); 78 (10.4); 77 (16.7).
Calcd for C9H11SO3Cl: C, 46.15; H, 4.74; S, 13.66; Cl,
14.94. Found: C, 46.29; H, 4.88; S, 13.47; Cl, 15.01%.
1
2). 4b: 68% H NMR: l 7.5–7.6 (m, 1H, Ar), 7.2–7.4 (m,
3H, Ar), 6.0 (m, 1H, CHꢀCH2), 5.6 (d, J=4 Hz, 1H,
CHOH), 5.3 (m, 2H, CH2ꢀCH), 3.1 (br. s., 1H, OH). 13C
NMR: l 140.4; 138.9; 130.0; 129.3; 128.2; 127.7; 116.2;
71.9. 4c: 1H NMR l 6.9–7.4 (m, 4H, Ar), 6.1 (m, 1H,
CHꢀCH2), 5.3 (m, 3H, CHꢁCHꢀCH2), 3.8 (s, 3H,
1
OCH3), 2.2 (br.s, 1H, OH). 4d: H NMR: l 5.9 (m, 1H,
CHꢀCH2), 5.2 (m, 2H, CH2ꢀCH), 3.9 (m, 1H, CHOH),
2.6 (br.s, 1H, OH), 1.8 (m, 1H, CH(CH3)2), 1.1 (m, 6H,
CH3); 13C NMR: l 139.4; 115.4; 78.6; 33.6; 17.8; 15.2.
11. Although episulfones are considered short lived interme-
diates in the R–B reaction, they can be deprotonated at
low temperature. The carbanions produced react with
aldehydes to form the aldols, with loss of SO2 giving
allylic alcohols, thus, episulfones behave as vinyl anion
equivalents.
Muccioli, A. B.; Simpkins, N. S. J. Org. Chem. 1994, 59,
5141.
1
12. 5a: H NMR: l 3.8 (s, 1H, CHSO2CH3), 2.9 (s+m, 3H,
SO2CH3), 2.0 (m, 2H, Cy), 1.5 (m, 8H, Cy). 13C NMR: l
73.0; 68.2; 40.8; 34.9; 28.0; 24.8; 24.7; 24.6. MS (EI 70
eV): m/z (%) 111 (20.0); 99 (31.3); 93 (100); 81 (90.0); 67
(67.7); 39 (44.4); 41 (43.7); 43 (31.8); 55 (71.3). Calcd for
C8H14SO3: C, 50.51; H, 7.42; S, 16.82. Found: C, 50.37;
H, 7.25; S, 16.76%. 5b: 1H NMR: l 3.8 (s, 1H,
CHSO2CH3), 3.0 (s, 3H, SO2CH3), 2.1 (m:qd, J1=7.5
1
Hz, J2:2.1 Hz, 2H, CH2CH3), 1.7 (:q, J% =7.4 Hz, 2H,
anti-2a: H NMR: l 7.3–7.5 (m, 5H, Ph); 5.2 (d, J=8.4
1
(CH2CH3)%), 1.1 (t, J1=7.5 Hz, 3H, CH2CH3), 0.9 (t,
Hz, 1H, CH(OH)); 4.8 (d, J=8.4 Hz, 1H, CH(SO2CH3));
3.1 (s, 3H, CH3), 1.7 (br. s, 1H, OH). 13C NMR: l 137.8;
129.1; 128.4; 127.4; 75.2; 73.8; 39.7. When the mixture
was warmed to 0°C before quenching, pure oxirane 3a
(trans:cis>98:2) was obtained (0.38 g, 96%). Recrystalliza-
tion from hexane/CH2Cl2 gave pure trans-3a: mp 86–
J% =7.4 Hz, 3H, (CH2CH3)%). 13C NMR: l 72.3; 70.8;
1
41.0; 27.1; 22.3; 9.7; 8.2. MS (EI 70 eV); m/z (%) 99
(12.0); 87 (13.4); 81 (17.6); 69 (30.8); 57 (36.1); 55 (32.3);
43 (100); 41 (61.3); 39 (15.3). Calcd for C7H14SO3: C,
47.17; H, 7.92; S, 17.6. Found: C, 47.10; H, 7.75; S,
17.70%. Molecular ions are absent in the MS of 5a and
5b.
1
87°C. H NMR: l 7.4 (m, 3H, Ph), 7.3 (m, 2H, Ph), 4.6
(d, J=1.6 Hz, 1H, PhCH), 4.3 (d, J=1.6 Hz, 1H,