aminals derived from (3S,4E,aR)-8 and (3R,4E,aR)-12 may be
rationalised by conformational minimisation of both syn-
pentane10 and 1,3-diaxial interactions in the chair transition
state. In this model, the nitrogen lone pair is assumed to occupy
preferably a position between the largest C(a)Ph and C(a)Me
substituents, anti to C(a)H, minimising the dominant syn-
pentane interaction with the trimethylsilyloxy group of the
ketene aminal. For rearrangement of the (Z)-N,O-silyl ketene
aminal from (3S,4E,aR)-8, this conformation enables the largest
C(a)Ph substituent to occupy a position anti to the N-allyl
fragment, with the C(a)Me group eclipsing the C(3)R sub-
stituent.11
Application of this transition state model to the mismatched
rearrangement indicates that the expected chair transition states
18 and 19 would be destabilised by 1,3 diaxial interactions
between the C(3)R group and the trimethylsilyloxy group in 18,
or syn-pentane interactions with the C(a)Ph substituent in 19.
The difference in energy between these and any alternative
transition states for the rearrangement is therefore diminished,
resulting in the observed low levels of diastereoselectivity upon
rearrangement.
In conclusion, the matched rearrangement configuration for
the substrates is readily achievable via the diastereoselective
conjugate addition of lithium (R)-N-allyl-N-a-methylbenzyla-
mide to a,b,g,d-unsaturated esters and its application to total
synthesis is being investigated further within our laboratory.12
The authors wish to thank the EPSRC and Rhoˆne-Poulenc
Rorer for funding (E. D. S) and New College, Oxford for a
Junior Research Fellowship (A. D. S).
Fig. 3 Chem 3D representation of the X-ray crystal structure of
(2S,3R,4E,aR)-13 (some H removed for clarity).
(2S,3R,4E,aR) configuration following from the known (R)-
configuration of N-a-methylbenzylamine.
To determine whether this highly diastereoselective re-
arrangement represented the matched or mismatched reaction
manifold, diastereomeric benzyl ether (3R,4E,aR)-12 was
subjected to rearrangement under identical conditions. Al-
though the reaction proceeded to high conversion by 1H NMR
spectroscopy, a complex inseparable mixture of three of the
possible eight diastereomeric g,d-unsaturated amide products
14–16 were produced in a 50 : 30 : 20 ratio. The relative
configurations contained within the diastereomeric products
14–16 were not unambiguously identified, but the mixture was
isolated in 51% yield after purification by chromatography
(Scheme 3).
Notes and references
† Crystal data for 13, C24H31NO2, M = 365.52, orthorhombic, space group
P212121, a = 4.9041(8), b = 14.4817(15), c = 31.335(7) Å, U = 2225.4
Å3, Z = 4, m = 0.532 mm. 2766 unique reflections (23 < q < 43); 2107
reflections used. wR2 = 0.0747; R1 = 0.0595 [I > 3s(I)]. CCDC 190887.
data in CIF or other electronic format.
1 For a review on [3,3]-sigmatropic rearrangements see D. Enders, M.
Knopp and R. Schiffers, Tetrahedron: Asymmetry, 1996, 7, 1847.
2 For a review on asymmetric Claisen rearrangements see H. Ito and T.
Taguchi, Chem. Soc. Rev., 1999, 28, 43.
3 T. Yamazaki, J. T. Welch, J. S. Plummer and R. H. Gimi, Tetrahedron
Lett., 1991, 32, 4267; J. T. Welch and S. Eswarakrishnan, J. Am. Chem.
Soc., 1987, 109, 6716; M. J. Kurth, O. H. W. Decker, H. Hope and M.
D. Yanuck, J. Am. Chem. Soc., 1985, 107, 443.
4 T. Tsunoda, O. Sasaki and S. Itoˆ, Tetrahedron Lett., 1990, 31, 727; T.
Tsunoda, S. Tatsuki, Y. Shiraishi, M. Akasaka and S. Itoˆ, Tetrahedron
Lett., 1993, 34, 3297.
5 P. Metz and B. Hungerhoff, J. Org. Chem., 1997, 62, 4442; P. Metz and
B. Hungerhoff, Tetrahedron, 1999, 55, 14941.
6 T. P. Yoon and D. W. C. Macmillan, J. Am. Chem. Soc., 2001, 123,
2911.
7 T. Tsunoda, S. Tatsuki, K. Kataoka and S. Itoˆ, Chem. Lett., 1994, 543;
S. Itoˆ and T. Tsunoda, Pure Appl. Chem., 1994, 66, 2071.
8 T. Tsunoda, M. Sakai, O. Sasaki, Y. Sako, Y. Hondo and S. Itoˆ,
Tetrahedron Lett., 1992, 33, 1651.
9 S. G. Davies and D. R. Fenwick, Chem. Commun., 1995, 1109.
10 The minimisation of syn-pentane interactions as a stereocontrol strategy
is well documented. For representative examples see W. R. Roush, J.
Org. Chem., 1991, 56, 4151; S. L. Schreiber and Z. Wang, J. Am. Chem.
Soc., 1985, 107, 5303; E. D. Mihelich, K. Daniela and D. J. Eickhoff, J.
Am. Chem. Soc., 1981, 103, 7690; I. Paterson and J. P. Scott, J. Chem.
Soc., Perkin Trans. 1, 1999, 1003.
Scheme 3 Reagents and Conditions: (i) LHMDS (1.5 eq), TMSCl (2 eq),
toluene, D.
These experiments clearly indicate that rearrangement of
(3S,4E,aR)-8 represents the synergistically matched reaction,
while rearrangement of the corresponding (3R,4E,aR)-12 the
mismatched case. The high levels of diastereoselectivity
observed upon rearrangement of (3S,4E,aR)-8 may be ration-
alised by the reaction proceeding via the (Z)-N,O-silyl ketene
aminal through the chair transition state 17 in which all alkyl
substitutents occupy pseudo-equatorial sites, which gives rise to
the observed (2S,3R,4E,aR)-configuration of g,d-unsaturated
amide 13. The double diastereoselectivity observed in the
rearrangement of the diastereomeric (Z)-N,O-silyl ketene
11 For a related rationale concerning the diastereoselectivity observed
upon rearrangement of a constrained N-allylketene N,O-acetal see M. J.
Kurth and O. H. W. Decker, J. Org. Chem., 1986, 51, 1377.
12 One of the referees required further proof that the N-a-methylbenzyl
group has
a beneficial effect upon the matched rearrangement
diastereoselectivity. The d.e.s obtained upon rearrangement of the N-
benzyl and N-isopropyl amide analogues were 84% and 75% d.e.
respectively and, as expected, fall in between those for the matched and
mismatched cases described herein.
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