Opening of a vinyl aziridine with p-toluenesulfonamide under TBAF catalysis: Synthesis of 3,4-diamino-3,4-dideoxy-L-chiro-inositol

Article abstract of DOI:10.1016/S0040-4039(01)01298-9

3,4-Diamino-3,4-dideoxy-L-chiro-inositol has been prepared from bromobenzene by a chemoenzymatic approach. The key chemical step was a tetrabutylammonium fluoride (TBAF) catalyzed vinyl aziridine opening employing p-toluenesulfonamide as a nucleophile, es

Full text of DOI:10.1016/S0040-4039(01)01298-9

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 6433–6435
Opening of a vinyl aziridine with p-toluenesulfonamide under
TBAF catalysis: synthesis of
3,4-diamino-3,4-dideoxy- -chiro-inositol
L
Bernhard J. Paul, Elizabeth Hobbs, Pablo Buccino and Tomas Hudlicky*
Department of Chemistry, University of Florida, PO Box 117200, Gainesville, FL 32611, USA
Received 9 July 2001; revised 17 July 2001; accepted 18 July 2001
Abstract—3,4-Diamino-3,4-dideoxy-L-chiro-inositol has been prepared from bromobenzene by a chemoenzymatic approach. The
key chemical step was a tetrabutylammonium fluoride (TBAF) catalyzed vinyl aziridine opening employing p-toluenesulfonamide
as a nucleophile, establishing the 1,2-trans relationship of the amino groups. © 2001 Elsevier Science Ltd. All rights reserved.
Unnatural inositol derivatives with amino groups sub-
stituted for one or more hydroxyl groups have attracted
interest as probes for the investigation of the inositol-
phosphate cycle as well as potential glycosidase
inhibitors, and several diaminocyclitol aminoglycosides
possess antibiotic activities. The aminocyclitol unit in
the great majority of these aminoglycoside antibiotics is
either 2-deoxystreptamine (1) or streptamine (2),1 both
featuring a 1,3-arrangement of the two amino groups
(Fig. 1).
Bromocyclohexadiene-cis-diol 38–10 was produced by
whole-cell fermentation of bromobenzene with E. coli
JM109(pDTG601) and converted in two steps to the
previously reported11–13 vinyl aziridine 4. Because the
three-step procedure for the vinyl aziridine opening
with azide, reduction and subsequent protection lacked
the desired brevity and was hampered by low yields, we
searched for alternatives to establish the desired 1,2-
trans relationship of the nitrogen atoms. The C2-sym-
metry of the target molecule prompted us to attempt
ring opening with p-toluenesulfonamide, despite its low
nucleophilicity, thus introducing nitrogen already in its
protected form and limiting deprotection to a single
step for both nitrogen moieties.
Several syntheses of streptamine derivatives containing
either a 1,3-2,3 or a 1,4 relationship4 of the nitrogen
atoms have been reported. The preparation of 1,2-
diamino analogs has been reported for muco-inositol,5
DL-chiro-6 and myo-inositol.7
TBAF14 is a powerful catalyst for the opening of epox-
ides with thiols,15 and it has been suggested that protic
substances can form hydrogen-bonded complexes with
fluoride ion, thus vastly enhancing the nucleophilicity
of the attacking species.16–18 TBAF has also been
reported to be an excellent catalyst for the opening of
aziridines with trialkylsilyl halides and pseudohalides.19
When an equimolar solution of vinyl aziridine 4 and
p-toluenesulfonamide (5) in DMSO was treated with
two equivalents of TBAF,20 the mixture was converted
to bis-sulfonamide 6 in a matter of minutes in 95%
yield (Scheme 1).
In this manuscript we wish to report a chemoenzymatic
approach to 3,4-diamino-3,4-dideoxy-L-chiro-inositol
by an unusual vinyl aziridine opening using p-toluene-
sulfonamide as the nucleophile and catalyzed by tetra-
butylammonium fluoride (TBAF).
This transformation was also accomplished with only
0.5 equivalents of the catalyst; however, the reaction
took several hours. With catalyst concentrations lower
than 20 mol%, some product resulting from the open-
ing of the vinyl aziridine with residual water was also
observed.
Figure 1. The structures of 2-deoxystreptamine (1) and strep-
tamine (2).
* Corresponding author. Tel.: (352)-392-9844; fax: (352)-846-1203;
e-mail: hudlicky@chem.ufl.edu
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)01298-9

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B. J. Paul et al. / Tetrahedron Letters 42 (2001) 6433–6435
Scheme 1. Reagents and conditions: (i) Refs. 11–13; (ii) 5, TBAF, DMSO; (iii) AIBN, Bu3SnH, THF; (iv) OsO4(cat.)/NMNO,
acetone, H2O; (v) DMP, H+; (vi) Na, NH3(l); (vii) HCl, MeOH.
Vinyl bromide 6 was then reduced under radical condi-
tions to provide alkene 7 (90%). The latter compound
was hydroxylated (OsO4(cat.)/NMNO) and the resulting
diol protected as its acetonide to yield the fully hydroxy-
lated species 8 in 75% yield over two steps. The
sulfonamide groups in 8 were removed under the condi-
tions of dissolving metal reduction (Na/NH3), followed
by deprotection of the ketals (HCl/MeOH) to provide
the title compound (9) as its bis-hydrochloride (47%
over two steps).21
catalysis to give 10 (route A). Furthermore, we have
found23 that benzylamine is also a suitable nucleophile
for the Yb(OTf)3-catalyzed ring opening to give 11
(route C). Finally, the (pseudo)-symmetric approach
described in this manuscript allows for the construction
of protected diamine 6, which has two identical protect-
ing groups (route B). These strategies enable us to
construct differently protected diamines from the same
precursor, thus allowing further functionalization of
either of the two amino groups.
This procedure further expands the scope of conditions
for vinyl aziridine openings, as shown in Scheme 2. As
we have recently shown,22 the opening of vinyl aziridine
4 can be accomplished with ammonia under Yb(OTf)3
In conclusion, we have shown that vinyl aziridine open-
ing can be accomplished with p-toluenesulfonamide as
the nucleophile by employing TBAF as catalyst.
Diamine 9 was synthesized from vinyl aziridine 4 in
four steps (six operations) in an overall yield of 34%.
The current focus of our research includes expanding
the scope of the TBAF-catalyzed aziridine opening, the
investigation of 9 as a potential glycosidase inhibitor,24
as well as the incorporation of derivatives of 9 into
potentially water-soluble salen-type catalysts. Progress
in these areas will be reported in due course.
Acknowledgements
The authors are grateful to the NSF (CHE-9615112,
CHE-9910412), the US Environmental Protection
Agency (R 826113) and TDC Research, Inc. for sup-
port of this work. P.B. wants to thank the Department
of Chemistry at the University of Florida for support of
the REU program.
References
Scheme 2. Different strategies for vinyl aziridine opening;
reagents and conditions: (i) NH3(l), Yb(OTf)3, sealed tube; (ii)
5, DMSO, TBAF; (iii) Yb(OTf)3, 1,4-dioxane, BnNH2.
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B. J. Paul et al. / Tetrahedron Letters 42 (2001) 6433–6435
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