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Phosphorus, Sulfur, and Silicon
and the Related Elements
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and subscription information:
http://www.tandfonline.com/loi/gpss20
Highly Stereoselective Tandem
Pummerer Reaction/-Hydroxy
Imine Rearrangement of E.P. -
Sulfinylenamines
Pierfrancesco Bravo , Marcello Crucianelli , Alessandro
Volonterio & Matteo Zanda
a
C.N.R. - C.S.S.O.N. Dipartimento di Chimica del
Politecnico , via Mancinelli 7, I-20131 Milano, Italy
b
C.N.R. - C.S.S.O.N. Dipartimento di Chimica del
Politecnico , via Mancinelli 7, I-20131 Milano, Italy
c
C.N.R. - C.S.S.O.N. Dipartimento di Chimica del
Politecnico , via Mancinelli 7, I-20131 Milano, Italy
d
C.N.R. - C.S.S.O.N. Dipartimento di Chimica del
Politecnico , via Mancinelli 7, I-20131 Milano, Italy
Published online: 17 Mar 2008.
To cite this article: Pierfrancesco Bravo , Marcello Crucianelli , Alessandro Volonterio &
Matteo Zanda (1997) Highly Stereoselective Tandem Pummerer Reaction/-Hydroxy Imine
Rearrangement of E.P. -Sulfinylenamines, Phosphorus, Sulfur, and Silicon and the Related
Elements, 120:1, 353-354, DOI: 10.1080/10426509708545545
To link to this article: http://dx.doi.org/10.1080/10426509708545545
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Phosphorus. Sulfur, and Silicon. 1997, Vol. 120 & 121, pp. 353-354 e 1997 OPA (Overseas Publishers Association)
Reprints available directly from the publisher Amsterdam E.V. Published in The Netherlands
Photocopying permitted by license only under license by Gordon and Breach Science Publishers
Printed in Malaysia
Highly Stereoselective Tandem Pummerer Reaction/
a-Hydroxy Imine Rearrangement of E.P. P-Sulfinylenamines
PIERFRANCESCO BRAVO, MARCELLO CRUCIANELLl/
ALESSANDRO VOLONTERIO AND MATTEO ZANDA
C.N.R. - C.S.S.O.N. Dipartimento di Chimica del Politecnico, via Mancinelli
7, 1-20131 Milano, Italy.
f
Dipartimento di Chimica, Ingegneria Chimica e
Materiali, Universita di L'Aquila, Via Vetoio, 1-67010, Italy
Abstract. The highly stereoselective tandem Pummerer reaction/a-hydroxy
imine rearrangement of E.P. a-fluoroalkyl-p-sulfmylenamines affording chiral
non-racemic fluoropyruvaldehydes iV.S-ketals is described.
The synthesis of fluorosubstituted organic fine chemicals is an important goal, owing
to the outstanding chemical and biomedicinal properties induced by the insertion of
fluorine. However, the stereoselective synthesis of fiuoroorganic molecules
represents a significant challenge for the chemist.
We have recently reported the synthesis of enantiomerically pure <x-
fluoroalkyl-p-sulfinylenamines 1, new useful fluorinated chiral templates.
1
Treatment of 1 with trifluoroacetic anhydride, followed by addition of silica gel
or of an aqueous NaHCC>3 solution, gives rise to a stereoselective tandem Pummerer
reaction/arylthio group migration, producing the corresponding fluoro
pyruvaldehydes /V,S-ketals 2 in high enantiomeric excess (figure 1 and table I).
2
*t O NHR j
NR
^ ? ' pTolS
. STEP1
1 a '. Re ~ CFi j R ~ Cbz ^ a p r
1
!? . T?
1
r*k-
r 3 -, t a . Kp Cr
3
; K Cuz
l b : R
F
= CF
3
; R = H 2 b : R p = CF
3
; R' = COCF
l c : R p = CF
2
H;R = Cbz 2 C : Rp = CF
2
H; R' = Cbz
1 d : Rp = CF
2
C1; R = Cbz 2 d : Rp = CF
2
C1; R' = Cb;
3
FIG. 1. Key: (i) TFAA, THF, 0C, 1 min; (ii) NaHCO
3
5% or SiO
2
/H
2
O (see table 1), 0C, 10 min.
353
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354 P. BRAVO, M. CRUCIANELLI, A. VOLONTERIO AND M. ZANDA
TABLE 1. Stereoselective formation of fluoropyruvaldehydes A^-ketals 2 from sulfoxides 1.
Enamine R
F
Product NaHCO
3
5%; e.e. (yield) SiO
2
thenH
2
Q; e.e. (yield)
(R)-(Z)-la CF
3
(+)-(R)-2a 68% (85%)
(5)-(Z)-la CF
3
(-)-(S)-2a 68 % (85 %)
CF
3
(+)<R)-2b 67% (88%)
CF
2
H (+)-(R)-2c 42 % (86 %)
CF
2
H (+)-(^)-2c 6% (86%)
(/?)-(Z)-ld CF
2
C1 (+)-(R)-2d not performed
74 % (49 %)
not performed
73 % (71 %)
62% (58%)
8 % (56 %)
79 % (70 %)
The formation of the intermediate imine 3 was confirmed by performing the
reaction in a NMR tube. Indeed, addition of trifluoroacetic anhydride (1 equiv) to a
THF-d
8
solution of enamine 1, resulted in the clean formation of 3, stable for several
days at room temperature.
In the light of these results, a reasonable mechanism for the stereoselective formation
of the aldehydes 2 from 1 involves a Pummerer reaction (step 1), followed by an a-
hydroxy imine rearrangement (step 2), both occurring with high stereoselection.
H^olS^X^
A
H OOCCFj
3
- CFjCOOH
FIGURE 2
H3C JH
The absolute stereochemistry of the aldehydes 2 has been determined by X-ray
crystallographic analysis of the enantiomerically
pure molecule 4, obtained by addition of
CUMgCl to (/J)-2a and subsequent
esterification with (+)-(5)-a-phenylpropionic
acid (figure 3).
CbzHN SpTol
4 FIGURE 3
REFERENCES
1. Arnone, A.; Bravo, P.; Capelli, S.; Meille, S. V.; Zanda, M; Cavicchio, G.;
Crucianelli, M., J. Org. Chem., 61, 3375 (1996).
2. Bravo, P.; Crucianelli, M.; Fronza, G.; Zanda, M., Synlett, 249 (1996).
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