A configurationally stable alkoxy allenyl zinc reagent, en route to anti-anti vicinal amino diols

Article abstract of DOI:10.1021/ol015941a

(formula presented) The reaction of an alkoxyallenyl zinc reagent with benzyl imines derived from lactic and mandelic acids proceeds highly diastereoselectively and leads to 2-amino-1,3-diol derivatives with an anti-anti pattern.

Full text of DOI:10.1021/ol015941a

ORGANIC
LETTERS
2001
Vol. 3, No. 12
1889-1891
A Configurationally Stable Alkoxy
Allenyl Zinc Reagent, en Route to
anti-anti Vicinal Amino Diols
Jean-Franc¸ois Poisson and Jean F. Normant*
Laboratoire de Chimie des Organoe´le´ments, UniVersite´ Pierre et Marie Curie,
4 place Jussieu 75252 Paris ce´dex 05, France
normant@moka.ccr.jussieu.fr
Received April 5, 2001
ABSTRACT
The reaction of an alkoxyallenyl zinc reagent with benzyl imines derived from lactic and mandelic acids proceeds highly diastereoselectively
and leads to 2-amino-1,3-diol derivatives with an anti-anti pattern.
We have recently shown that allenylzinc reagents derived
from lithiated 1-trimethylsilyl-1-alkynes react diastereo-
selectively with chiral R-alkoxy imines.1 Those imines were
used first to demonstrate the good configurational stability
of the allenylzinc species at temperatures up to -10 °C2 and
second to form an enantioenriched allenyl zinc by kinetic
resolution.3 To extend the scope of this methodology, we
were then interested in studying the case of allenylzinc
reagents derived from propargylic ethers. These reagents have
been little studied so far.
tivities (d.r. < 4:1).4 More recently, Yamamoto et al. have
obtained analogous selectivities.5
To our knowledge, reagents of type 1 have not yet been
reacted with imines. We started up with alkoxyallenylzinc
2. This organozinc is prepared from its lithiated analogue,
which is kept at -70 °C during the Li/Zn exchange to avoid
any Wittig [1,2] rearrangement (Scheme 2).6
As could be anticipated from our previous studies1 (and
the above-mentioned results),4,5 the reaction of alkoxy-
allenylzinc 2 with a silyl-protected R-alkoxy aldehyde
derived from (()-mandelic acid led to a low diastereo-
selectivity: three diastereomers (48:33:19) were formed. We
Epsztein et al. have shown that reagents 1 (Scheme 1) react
with aldehydes in good yields but with low diastereoselec-
(1) Poisson, J.-F.; Normant, J. F. J. Org. Chem. 2000, 65, 6553-6560.
(2) Poisson, J.-F.; Chemla, F.; Normant, J. F. Synlett 2001, 305-307.
(3) Poisson, J.-F.; J. F. Normant J. Am. Chem. Soc. 2001, 123, 4639-
4640.
Scheme 1
(4) (a) Mercier, F.; Epsztein, R.; Holland, S. Bull. Soc. Chim. Fr. 1972,
690-696. (b) Chwastek, H.; Epsztein, R.; Le Goff, N. Tetrahedron 1973,
29, 883-889. For an addition to a ketone, see: (c) Evans, D. A.; Nelson,
J. V. J. Am. Chem. Soc. 1980, 102, 774-780.
(5) (a) Ishiguro, M.; Ikeda, N.; Yamamoto, H. J. Org. Chem. 1982, 47,
2225-2227. (b) Hiraoka, H.; Furuta, K.; Ikeda, N.; Yamamoto, H. Bull.
Chem. Soc. Jpn. 1984, 57, 2777-2780.
(6) Tomooka, K.; Yamamoto, H.; Nakai, T. Liebigs Ann./Recueil 1997,
1275-1281.
10.1021/ol015941a CCC: $20.00 © 2001 American Chemical Society
Published on Web 05/12/2001

Scheme 2a
Scheme 4a
a (a) HF‚(NEt3)3, CH3CN, rt, 70%; (b) HCl (12 N), MeOH, 90%;
(c) (MeO)2CMe2, CSA.
a (a) sec-BuLi, THF, -70 °C; (b) ZnBr2 (1 M/THF), -70 °C.
The anti-anti relationship in aminodiols 5 and 6 corre-
sponds to the general outcome already observed with non-
oxygenated allenyl zinc reagents.1 This diastereoselectivity
can similarly be explained by the attack of the imine function
according to the Felkin-Ahn model and by a cyclic transition
state, where the imine nitrogen is chelated by the Zinc atom,
leaving the substituent of the allene (OMOM) and the imine
in anti position in order to minimize the steric interaction
(Figure 1).
thus turned to the corresponding benzylimines 3 and 4
derived from mandelic and lactic aldehydes. To our delight,
a unique diastereomer is formed in good yield in each case
(Scheme 2). We then checked the relative configuration of
the obtained aminodiols. Aminodiol 6 was converted into
trifluoroacetamide 7, and the resulting product was treated
with TBAF, leading to crystalline oxazolidinone 8 via a ring
closure with liberation of fluoroform (Scheme 3).7 The X-ray
Scheme 3a
Figure 1.
We then tried to evaluate the configurational stability of
reagent 1 by means of the Hoffmann test. Historically, this
test was first performed on an alkoxy allenyl titanate.8
Subsequently, Hoppe et al. studied metalated propargylic
carbamates and have shown that the organotitanates are
configurationally more stable than their lithio counterparts.9
In our case, the slow addition of enantiomerically enriched
imine 3 to reagent 2 in THF, at -70 °C, led to a 75:25
mixture of two diastereomers in 53% yield, accompanied
by 30% of the starting material. The large proportion of
unreacted product could point to a possible kinetic resolution
due to the low reactivity of the mismatched pair. To avoid
such a drawback, Hoffmann recommends to carry out an
inverse addition, so that the organometallic is maintained in
an excess of electrophile.10 Indeed, slow addition of 2 to the
imine (R)-3, at -50 °C, gives a 50:50 mixture of both
isomers in 65% yield (Scheme 5).
a (a) (CF3CO)2O, DIEA, CH2Cl2, 95%; (b) TBAF (1 M/THF),
80%
pattern of this oxazolidinone shows a cis relationship between
the two substituents in the cycle (confirming the 1H spectral
data) and an anti relationship between the two other
asymmetric centers. The relative configuration of 5 is
therefore anti-anti.
For compound 6 our strategy relied on the formation of
acetonide 10, obtained by desilylation of 6, followed by HCl-
mediated deprotection of the MOM ether, and treatment with
the dimethoxy acetal of acetone under acid catalysis (Scheme
3
4). The J coupling constants of 9.9 Hz between the three
hydrogens lying on this 1,3-dioxane showed that all substit-
uents on the cycle occupied equatorial positions, demonstrat-
ing the anti-anti relationship in 6.
(8) Hoffman, R.; Lanz, J.; Metternich, R.; Tarara, G.; Hoppe, D. Angew.
Chem., Int. Ed. Eng. 1987, 26, 1145-1146.
(9) Dreller, S.; Dyrbusch, M.; Hoppe, D. Synlett 1991, 397-400.
(10) Hoffmann, Configurationally Stable and Configurationally Labile
Chiral R-Substituted Organolithium Compounds in Stereoselective Trans-
formation. In Organic Synthesis Via Organometallics (OSM4); Enders, D.,
Gais, H.-J., Keim, W., Eds.; Vieweg: Braunschweig, 1993; pp 79-91.
(7) For reactions of CF3 with amides see: (a) Folle´as, B.; Marek, I.;
Normant, J. F.; Saint-Jalmes, L. Tetrahedron 1998, 39, 2973-2976. (b)
Large, S.; Roques, B.; Langlois, B. R. J. Org. Chem. 2000, 65, 8848-
8856.
1890
Org. Lett., Vol. 3, No. 12, 2001

Scheme 5
Scheme 6a
a (a) BH3.Me2S, NaBH4 cat., THF, 80%; (b) TBDMSCl, imid-
azole, DMAP cat., DMF, quant; (c) PPTS, MeOH, 75%; (d) PCC,
CH2Cl2, 80%; (e) BnNH2, MgSO4, toluene, 0 °C, quant.
resolution would be sufficiently high, so that the slow
addition of the imine (S)-12, to a slight excess of reagent 2,
would deliver a unique enantiomer of 13. Such is the case
using 4 equiv of the alkoxyallenylzinc (2 equiv of one
enantiomer): 13 is obtained in an excellent 86% yield as a
single diastereomer, enantiomerically enriched, with the
desired O-N-O-connections (Scheme 7).
The configuration of the second diastereomer has not been
determined but is considered to be analogous (anti-syn) to
those previously studied with non-oxygenated allenyl zinc
reagents.2,11 We can thus conclude that the configurational
stability of 2 is important at a temperature up to -50 °C.
At this point we have shown that alkoxyallenylzinc 2 reacts
diastereoselectively with racemic R-chiral imines and is
configurationally stable at a temperature up to -50 °C. The
addition of this organozinc to R-alkoxy imines leads to anti-
anti 1,3-diamino-2-hydroxy derivatives, a scaffold present
in many important classes of natural products, particularly
when heterocycles are involved, for instance, polyhydroxyl-
ated pyrolizidines such as castanospermine, australine or
casuarine, which are known glycosidase inhibitors.12 Our
approach should prove straightforward, for example, in the
elaboration of the first three stereocenters of 10, a known
precursor of 1-epicastanospermine (Figure 2).12a
Scheme 7
In summary, the configurationally stable alkoxyallenylzinc
2 displays an excellent kinetic resolution in its reaction with
a non-racemic R-silyloxyimine and allows a straightforward
access to 1,3-dialkoxy-2-amines, presenting an anti-anti
pattern. Further synthetic applications of this approach are
underway.
Figure 2.
Acknowledgment. We gratefully acknowledge Rhoˆne-
Poulenc Rorer for financial support to J.-F. P.
To illustrate such a strategy, we first prepared enantio-
enriched imine (S)-12,13 from (S)-methylmalate 11, according
to Scheme 6. Knowing that organozinc reagent 2 was
configurationally stable, we anticipated that the kinetic
Supporting Information Available: Spectral data for all
compounds, Ortep diagram and crystallographic table of 8.
This material is available free of charge via the Internet at
http://pubs.acs.org.
(11) Marshall, J. A.; Chobanian, H. R. J. Org. Chem. 2000, 65, 8357-
8360.
OL015941A
(12) (a) Kibayashi, C.; Ina, H. J. Org. Chem. 1993, 58, 52-61. (b)
Denmark, S. E.; Martinborough, E. A. J. Am. Chem. Soc. 1999, 121, 3046-
3056. (c) Denmark, S. E.; Hurd, A. R. J. Org. Chem. 2000, 65, 2875-
2886. (d) Denmark, S. E.; Herbert, B. J. Org. Chem. 2000, 65, 2887-
2896. (e) Romero, A.; Wong, C. H. J. Org. Chem. 2000, 65, 8264-8268.
(13) For another preparation of the aldehyde, see: (a) Singer, R. A.;
Shepard, M. S.; Carreira, E. M. Tetrahedron 1998, 54, 7025. (b) Solladie´,
G.; Wilb, N.; Bauder, C.; Bonini, C.; Viggiani, L.; Chiummiento, L. J.
Org. Chem. 1999, 64, 5447-5452.
Org. Lett., Vol. 3, No. 12, 2001
1891