Pd(II)-catalyzed rearrangement of propargyl phosphori-
midates F (Scheme 1, path f).9 A complementary strategy
relies on the [2,3]-sigmatropic rearrangement of propargyl
sulfimides G leading to N-allenylsulfenimides (Scheme 1,
path g).10 Another recently investigated class of precursors
are ynamides11 possessing a propargylic alcohol (hereafter
referred to as “ynamido-alcohols”), as illustrated with the
[2,3]-sigmatropic rearrangement of phosphites H leading
to R-aminoallenylphosphonates (Scheme 1, path h)12 and
the Pd(0)-catalyzed coupling of propargylic carbonates I
with arylboronic acids (Scheme 1, path i).13 However, the
preparation of enantiomerically enriched functionalized
allenamides with respect to axial chirality has only been
achieved byroute (c) relying on a chiral auxiliary,5 route(e)
using enantioenriched allenyl halides whose preparation is
not trivial,7b and routes (f) and (g) by chirality transfer.9,10
rearrangement leading to aminodienes L.16 This work
prompted us to disclose our results, and we report herein
the first synthesis of highly functionalized allenamides O
using the ester-enolate Claisen rearrangement of glycinates17
M derived from N-sulfonyl ynamido-alcohols as well
as their use for the synthesis of substituted pyrrolidines
(Scheme 2).
Scheme 2. Claisen Rearrangement of Ynamido-Alcohol
Derivatives
Scheme 1. Synthetic Routes toward Allenamides
Propargylicglycinate2awas selectedasthetestsubstrate
and was readily prepared by copper-catalyzed cross-cou-
pling between bromoalkyne 1a, derived from but-3-yn-2-
ol, and N-benzyl sulfonamide.18 As reported recently,12
this coupling reaction could be carried out with the free
alcohol, but to avoid long reactions times and obtain
satisfactory yields of the coupling products in all the
investigated cases, we found that a 3-fold increase of the
copper salt and ligand loadings was beneficial. Subsequent
esterification of the intermediate ynamido-alcohol with
N-Boc glycine provided glycinate 2a (63%, two steps from
1a). The chelated R-amino zinc enolate P was generated
from glycinate 2a by treatment with LiHMDS (THF,
ꢀ78 °C) followed by the addition of ZnCl2.17b,c Subse-
quent enolate-Claisen rearrangement proceeded smoothly
(ꢀ78 °C, 2 h) and led to the corresponding stable car-
boxylic acid 3a which did not undergo decarboxylation, by
contrast with the behavior of compounds J.19 Carboxylic
acid 3a was converted to the corresponding methyl ester
(MeI, K2CO3, DMF, rt) to afford allenamide 4a, but the
diastereoselectivity of the rearrangement was difficult to
evaluate due to the presence of rotamers (Boc group).
Cyclization of the crude allenamide 4a could be accom-
plished under remarkably mild conditions by treatment
Despite the synthetic potential of Claisen rearrangements
involving derivatives of propargyl alcohols as a route to
allenes,14 the possibility to access allenamides by a [3,3]-
sigmatropic rearrangement involving ynamido-alcohol
derivatives has not been demonstrated yet.15 Recently,
Carbery and Heffernan reported that an IrelandꢀClaisen
rearrangement applied to arylacetates J did not lead to the
expected allenamide carboxylic acids K because these
compounds underwent spontaneous decarboxylative
(9) Danowitz, A. M.; Taylor, C. E.; Shrikian, T. M.; Mapp, A. K.
Org. Lett. 2010, 12, 2574–2577.
(10) (a) Armstrong, A.; Cooke, R. S.; Shanahan, S. E. Org. Biomol.
Chem. 2003, 1, 3142–3143. (b) Armstrong, A.; Emmerson, D. P. G. Org.
Lett. 2009, 11, 1547–1550.
(11) For reviews on ynamides, see: (a) DeKorver, K. A; Li, H.;
Lohse, A. G.; Hayashi, R.; Lu, Z.; Zhang, Y.; Hsung, R. P. Chem. Rev.
2010, 110, 5064–5106. (b) Evano, G.; Coste, A.; Jouvin, K. Angew.
Chem., Int. Ed. 2010, 49, 2840–2859.
(16) Heffernan, S. J.; Carbery, D. R. Tetrahedron Lett. 2012, 53,
5180–5182. Rearrangement of a propionate derived from an ynamido-
alcohol also led to an aminodiene instead of an allenamide.
(12) Gomes, F.; Fadel, A.; Rabasso, N. J. Org. Chem. 2012, 77, 5439–
5444.
(17) (a) Castelhano, A. L.; Horne, S.; Taylor, G. J.; Billedeau, R.;
€
Krantz, A. Tetrahedron 1988, 44, 5451–5466. (b) Kazmaier, U.; Gorbitz,
(13) Cao, J.; Kong, Y.; Deng, Y.; Lai, G.; Cui, Y.; Hu, Z.; Wang, G.
Org. Biomol. Chem. 2012, 10, 9556–9561.
C. H. Synthesis 1996, 1489–1493. (c) Zumpe, F. L.; Kazmaier, U. Synlett
1998, 434–436. (d) Mitasev, B.; Brummond, K. M. Synlett 2006, 3100–
3104.
(18) Zhang, Y.; Hsung, R. P.; Tracey, M. R.; Kurtz, K. C. M.; Vera,
E. L. Org. Lett. 2004, 6, 1151–1154.
(14) (a) The Claisen Rearrangement. Methods and Applications;
Nubbenmeyer, U., Hiersemann, M., Eds.; Wiley-VCH: Wienheim, 2007.
ꢀ
(b) For a recent review, see: Trejedor, D.; Mendez-Abt, G.; Cotos, L.; García-
Tellado, F. Chem. Soc. Rev. 2013, 42, 458–471.
(19) The different reactivity seems to be due to the nature of
the electron-withdrawing group on the nitrogen atom since the
IrelandꢀClaisen rearrangement of an arylacetate derived from a
N-tosyl ynamido-alcohol was not followed by decarboxylation; see
Supporting Information for a comparison of the reactivity.
(15) For sigmatropic rearrangements of the related enamido allylic
alcohols, see: (a) Ylioja, P. M.; Mosley, A. D.; Charlot, C. E.; Carbery,
D. R. Tetrahedron Lett. 2008, 49, 1111–1114. (b) Barbazanges, M.;
Meyer, C.; Cossy, J.; Turner, P. Chem.;Eur. J. 2011, 17, 4480–4495.
Org. Lett., Vol. 15, No. 7, 2013
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