Synthesis of chiral aminosulfite and sulfite from optically active 2-naphthol derivatives

Article abstract of DOI:10.1080/10426507.2010.527310

Preparation of chiral cyclic aminosulfite and sulfite derived from diastereomerically pure 1-[α-N-1-phenylethyl]benzyl-2-naphthol and 1,1′-bi-2′-naphthol, respectively, are reported. The nucleophilic substitution on the sulfite substrate by using some selected nucleophiles is also discussed. Copyright Taylor and Francis Group, LLC.

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Phosphorus, Sulfur, and Silicon and the
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Synthesis of Chiral Aminosulfite and
Sulfite from Optically Active 2-Naphthol
Derivatives
Professor Jozef Drabowicz a b , Miss Dorota Krasowska a , Miss Anna
Aftyka a , Dr Bernard Marciniak b & Dr Ewa Rozycka-Sokolowska b
a Center of Molecular and Macromolecular Studies, Polish Academy
of Sciences , Łodz, Poland
b Jan Dlugosz University in Czestochowa , Czestochowa, Poland
Published online: 12 Jul 2011.
To cite this article: Professor Jozef Drabowicz , Miss Dorota Krasowska , Miss Anna Aftyka , Dr Bernard
Marciniak & Dr Ewa Rozycka-Sokolowska (2011) Synthesis of Chiral Aminosulfite and Sulfite from
Optically Active 2-Naphthol Derivatives, Phosphorus, Sulfur, and Silicon and the Related Elements,
186:5, 1263-1267, DOI: 10.1080/10426507.2010.527310
To link to this article: http://dx.doi.org/10.1080/10426507.2010.527310
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Phosphorus, Sulfur, and Silicon, 186:1263–1267, 2011
Copyright ꢀC Taylor & Francis Group, LLC
ISSN: 1042-6507 print / 1563-5325 online
DOI: 10.1080/10426507.2010.527310
SYNTHESIS OF CHIRAL AMINOSULFITE AND SULFITE
FROM OPTICALLY ACTIVE 2-NAPHTHOL DERIVATIVES
Jozef Drabowicz,1,2 Dorota Krasowska,1 Anna Aftyka,1
Bernard Marciniak,2 and Ewa Rozycka-Sokolowska2
1Center of Molecular and Macromolecular Studies, Polish Academy of Sciences,
Łodz, Poland
2Jan Dlugosz University in Czestochowa, Czestochowa, Poland
Abstract Preparation of chiral cyclic aminosulfite and sulfite derived from diastereomeri-
cally pure 1-[α-N-1-phenylethyl]benzyl-2-naphthol and 1,1ꢁ-bi-2ꢁ-naphthol, respectively, are
reported. The nucleophilic substitution on the sulfite substrate by using some selected nucle-
ophiles is also discussed.
Keywords Aminosulfites; BINOL; chiral cyclic sulfinyl derivatives; nucleophilic substitution;
sulfites
INTRODUCTION
An approach based on the two consecutive reactions between the chiral cyclic sulfiny-
lating agents 1a,b and two different nucleophiles constitutes an efficient way to afford chiral
sulfinyl derivatives (diastereomerically pure 2 and enantiomerically pure 3, respectively).1
Because a phenolate is known as a very efficient leaving group, cyclic aminosulfite or
sulfite structures derived respectively from aminophenols or biphenols should be expected
to be more efficient sulfinylating agents as the aliphatic aminoalcohols or diols derivatives.
Thus, we decided to synthesize as the model structures an aminosulfite derived from
Received 20 July 2010; accepted 22 September 2010.
The authors would like to thank one of the referees for very constructive comments. This work was financially
supported (grants to J.D.) by government found created to support science in the 2009–2012 period (grant N N204
144437).
Address correspondence to Jozef Drabowicz, Center of Molecular and Macromolecular Studies, Polish
Academy of Sciences, Sienkiewicza 112 90-363, Łodz, Poland. E-mail: draj@cbmm.lodz.pl
1263

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J. DRABOWICZ ET AL.
diastereomeric, enantiopure 1-[α-N-1-phenylethyl]benzyl-2-naphthol2 and sulfite derived
from 1,1ꢁ-bi-2-naphthol3 (racemic or enantiopure) and to study the reactivity of the later
towards some selected nucleophilic reagents. The outcome of these preliminary experiments
will be presented below.
RESULTS AND DISCUSSION
Aminosulfites Derived from Enantiopure
1-[α−N-1-Phenylethyl]benzyl-2-naphthol
Earlier, small scale reactions of thionyl chloride with the (R,R) enantiomer of aminon-
aphthol 4 performed in the presence of a tertiary amine at temperatures from −70◦C to room
temperature in diethyl ether, were found to give the expected aminosulfite 5 as a mixtures
of diastereomers in yields above 90% and with diastereomeric excesses (de) below 30%.
All attempts to isolate a pure diastereoisomer from these mixtures (or a mixture strongly
enriched in a particular diastereomer) by typical crystallization have been unsuccessful.
However, it was possible to isolate, in some experiments, the pure diastereomers by par-
tition of the diastereomers in petroleum ether (due to the different solubility) occurring
effectively during a few hours stirring of their suspensions in this solvent.4 We were able
to carry out an X-ray structural analysis for the pure diastereomer having optical rotation
equal to [α]D = −75.2 (CH2Cl2). It showed a slightly distorted tetrahedral rearrangement
of the substituents (two oxygens, one nitrogen, and a lone electron pair) and the (S) abso-
lute configuration at the sulfinyl sulfur atom.5 To isolate the pure diastereomer having the
(R) absolute configuration at the sulfinyl sulfur atom, we carried out reactions of thionyl
chloride with the (S,S) enantiomer of aminonaphthol 4 under various reaction conditions
(given in Table 1). In this case, the expected amidosulfite 5 was formed now as a mixture
of diastereomers with, again, diastereomeric excesses (de) below 30% (see Table 1). The
almost pure diastereomer S,S,SS-5 (de > 95%) having optical rotation equal to [α]D = +
289.8 (CH2Cl2) was isolated in 19% yield by column chromatography of the crude sample
having 24% de (Scheme 1).
The Sulfite Derived from Binol and Its Reactions
with Selected Nucleophiles
The cyclic sulfite derived from enantiopure BINOL can be envisioned as a good
substrate for the generation of acyclic, diasteromeric sulfinyl derivative via the stereose-
lective nucleophilic substitution at the sulfinyl sulfur atom due to good leaving ability of
Table 1 Reactions of thionyl chloride with the (S,S) enantiomer of aminonaphthol 4 under various reaction
conditions
Base
Temp (◦C)
Yielda (%)
drb
i-PrMgBr
NaH:Et3N
1:1,05
NaH:Et3N
1:1,05
0◦C
0◦C
12
72
55:45
55:45
−78◦C
65
79
57:43
62:38
Et3N (4 eq mol)
0◦C
aFor a crude product.
bFrom the 1H NMR recorded for a crude product.

SYNTHESIS OF CHIRAL AMINOSULFITE AND SULFITE
1265
Scheme 1
a naphthoxy residue. In order to verify this expectation, we worked out an independent
protocol for the preparation 1,1ꢁ-binaphthyl-2,2ꢁ-diyl sulfite 7 starting from racemic and
enantipure (+)-(R)-BINOL-6 and carried out the model nucleophilic substitution reactions.
The synthesis of 1,1ꢁ-binaphthyl-2,2’-diyl sulfite 7 as (+)-isomer (from (-)-(S)-BINOL)
was described in the literature by Zhang et al.5 However, the product was obtained in poor
yield (18%) and only after column chromatography. It should be noted here that informa-
tion on that synthesis (published in Chinese) is still not available in the Beilstein database,
though we did find it in the SciFinder scholar database unexpectedly, only after working
out our procedure, in which we used diethyl ether as a solvent and triethylamine as a
base (insead of methylene chloride and pyridine). Our procedure gave both racemic and
optically active (R)-(-)- isomer almost quantitatively (Scheme 2). Racemic and optically
active derivatives are stable and could be stored at ambient temperature for months. We
were able to redetermine the crystal structure of the optically active (R)-(-) sulfite isomer
with an optical rotation [α]D = −647 (2.7, THF).
Scheme 2
Reactions of the Sulfite 7 with Selected Nucleophiles
Knowing from our previous work6 that it is possible to stop the reaction of dialkyl sul-
fites with Grignard reagents at the stage of a sulfinate formation if tertiary Grignard reagents
are used, we decided to find the reaction of sulfite 7 with tert-butylmagnesium chloride,
hoping that it will result in the highly diastereoseletive formation of the corresponding O-
aryloxy tert-butanesulfinate 8 (Scheme 3). The presence of the expected tert-butylsulfinate

1266
J. DRABOWICZ ET AL.
Scheme 3
8 (from traces to 33% yield) was confirmed by 1H NMR and MS spectra in crude reaction
products of all reactions which were carried out with two (or more) equivalents of tert-
butylmagnesium chloride. Unfortunately, all attempts to isolate and fully characterize this
sulfinate were until now unsuccessful. Very low yields of the desired sulfinate 8 in crude
reaction mixtures are undoubtedly due to its greater reactivity towards tert-butylmagnesium
chloride as compared with that of the starting sulfite. This should lead to the formation of
di-tert-butylsulfoxide, the presence of which in the crude reaction mixtures was supported
by their 1H NMR spectra.
Sodium methoxide, diisopropylamine, and triethylamine were also checked as nu-
1
cleophiles in the reaction with the sulfite 7. The reaction courses followed by H NMR
and polarymetry (based on analyzing the chemical shifts of selected aromatic absorption
and dramatic changes in the observed optical rotations of the sample solutions) suggested
the very rapid formation of acyclic, diastereomeric sulfinyl derivatives 9–11 as reaction
intermediates (Scheme 4).
Scheme 4
CONCLUSIONS
The reactions of diastereiomeric enantiopure 1-[α-N-1-phenylethyl]benzyl-2-
naphthols or the racemic or enantipure BINOL with thionyl chloride led to the
corresponding aminosulfite or sulfite diastereomers, respectively. The sulfite was found
to be very reactive towards selected nucleophilic reagents. The reaction courses that were
followed by means of 1H NMR and polarimetry revealed very rapid formation of acyclic,
diasteomeric sulfinyl derivatives 9–11 as the reaction intermediates.

SYNTHESIS OF CHIRAL AMINOSULFITE AND SULFITE
1267
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