Organic & Biomolecular Chemistry
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intermediate II, where elimination precedes ROH attack, in which
case the bonding with the alcohol would fix the stereochemistry.
Alternatively, in a concerted process for attack of ROH and
elimination of PhI (I →SN), the sulfur configuration would be
expected to be set in the initial nitrene attack. Therefore, considering
the observed (Ss)-stereochemistry of 6c, it is reasonable to consider
two possible stereo-determining steps – the attack of N or the attack
of O.
reaction, the two faces of the LUMO orbital have been considered
DOI: 10.1039/D0OB00647E
(Figure 3). Since one of the faces is easily accessible while the other
is affected by the steric hindrance and, perhaps, also by electronic
repulsion of the CH2OAc group, it is reasonable to assume that the
nucleophile could discriminate between the two faces. However, this
result cannot alone distinguish between the two proposed pathways
(Scheme 3), which remains an unanswered question.20, 21
Conclusions
In conclusion, a method for the synthesis of new glycosyl NH-
sulfoximines has been developed by using a highly chemo and
stereoselective one-pot O and NH transfer to the sulfur atom of β-
thioglycosides. This method allows for a straightforward preparation
of carbohydrate structures bearing a sulfoximine group bound to the
anomeric carbon. This protocol was applied to diverse
thioglycosides, and proved to be feasible to disaccharides such as
lactose, and to glycosylsulfenamides. X-Ray analysis confirmed the
structure and established the stereochemistry of one glycosyl
sulfoximine, while DFT calculations helped to rationalise the
stereoselectivity of the transformation. Further investigations are
ongoing on the use of these new and interesting glycosyl
sulfoximines.
Acknowledgements
We would like to thank the University of Bari for supporting this
research, and Ms. Arianna Franco for the precious synthetic
contribution. We thank The Royal Society for a University Research
Fellowship, UF140161 (to J.A.B.).
Notes and references
1
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Scheme 3. Proposed mechanism and stereoselectivity.
To shed some light on this stereoselective reaction, we ran DFT
calculations at (SMD(MeOH)/B3LYP/6-311++g** level, Gaussian 09),
on the thioglycoside 5c, and on the corresponding SN intermediate
II (Scheme 3). In both cases, it is possible to identify in the optimized
structures a less hindered side with lower steric demand around the
S atom (Scheme 3). Interestingly, the approach from the less
hindered side of the iodonitrene on 5c, or the solvent ROH on
intermediates II, would both lead to the observed (S)S
stereochemistry in the final product 6c. The geometry of II was
optimized by minimizing the energy with respect to all the
geometrical parameters, without imposing any molecular symmetry
constraints. Vibrational analysis, HOMO-LUMO orbitals calculations
and NPA analysis were also carried out. In the optimized structure,
the geometry around the sulfur atom is almost planar, with two
similar C-S bonds lengths (1.93 and 1.94 Å) while the C-N is a multiple
bond (1.48 Å). Moreover, according to the NPA analysis the S atom
bears the maximum positive charge (see Supplementary material).
The small HOMO-LUMO energy gap reflects the high reactivity of the
intermediate with tree HOMO orbitals almost degenerates, and the
LUMO well separated from the other virtual orbitals. The
corresponding 3-D plots showed that the HOMO orbitals are all
delocalized over the molecule while the LUMO orbital is a localized
2
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