oximes have been scrutinized in only a very limited way.9
Herein, we record several specific features associated with
proximal positioning of a carbonyl group to the spirocyclic
center and detail an unexpected interdependency involving
the acid initiator and ultimate migratory pathway.
Scheme 1
Oxidation of the known dextrorotatory diol 1010 with the
Dess-Martin periodinane11 furnished (-)-diketone 11 in
good yield (Scheme 1). Subsequent heating of (-)-11 with
hydroxylamine hydrochloride in ethanol containing pyridine
gave rise to a chromatographically separable 1:1 mixture of
(-)-9 and (-)-12. As a direct consequence of the C2
symmetry about the quaternary carbon in 11,12 the particular
carbonyl group undergoing oximation is irrelevant. The syn
and anti configurational assignments to the monoximes rest
on their ring-expansion chemistry (to be detailed below) and
additional intercorrelation with (+)-8.13,14
At this point, we addressed the response of 9 and 12 to
the action of PPA,15 Eaton’s reagent,16 PPE,17 and PPSE18
(1) Gawley, R. E. Org. React. 1988, 35, 1.
(2) Mazur, R. H. J. Org. Chem. 1961, 26, 1289.
(3) Wakabayashi, N.; Waters, R. M.; Law, M. W. Org. Prep. Proced.
Int. 1974, 6, 203.
(4) (a) Kuramoto, M.; Tong, C.; Yamada, K.; Chiba, T.; Hayashi, Y.;
Uemura, D. Tetrahedron Lett. 1996, 37, 3867. (b) Arimoto, H.; Hayakawa,
J.; Kuramoto, M.; Uemura, D. Tetrahedron Lett. 1998, 39, 861.
(5) Chou, T.; Kuramoto, M.; Otani, Y.; Shikano, M.; Yazawa, K.;
Uemura, D. Tetrahedron Lett. 1996, 37, 3871.
(6) For other synthetic studies relating to 6 and 7, consult: (a) Christie,
H. S.; Heathcock, C. H. Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 12079.
(b) Hayakawa, I.; Arimoto, H.; Uemura, D. Heterocycles 2003, 59, 441.
(b) Hayakawa, I.; Arimoto, H.; Uemura, D. Chem. Commun. 2004, 1222.
(c) Matsumura, Y.; Aoyagi, S.; Kibayashi, C. Org. Lett. 2003, 5, 3249. (d)
Hurley, P. B.; Dake, G. R. Synlett 2003, 2131. (e) Cason, M. W.; Kim, G.;
Danishefsky, S. J. Angew. Chem., Int. Ed. 2001, 40, 4453. (f) Carson, M.
W.; Kim, G.; Hentemann, M. F.; Trauner, D.; Danishefsky, S. J. Angew.
Chem., Int. Ed. 2001, 40, 4450. (g) Yokato, W.; Shindo, M.; Shishido, K.
Heterocycles 2001, 54, 871. (h) White, J. D.; Blakemore, P. R.; Korf, E.
A.; Yokochi, A. F. T. Org. Lett. 2001, 3, 413. (i) Trauner, D.; Churchill,
D. G.; Danishefsky, S. J. HelV. Chim. Acta 2000, 83, 2344. (j) Wright, D.
L.; Schulte, J. P., II.; Page, M. A. Org. Lett. 2000, 2, 1847. (k) Koviach, J.
L.; Forsyth, C. J. Tetrahedron Lett. 1999, 40, 8529. (l) Clive, D. L. J.;
Yeh, V. S. C. Tetrahedron Lett. 1999, 40, 8503. (m) Lee, S.; Zhao, Z.
Tetrahedron Lett. 1999, 40, 7921. (n) Lee, S.; Zhao, Z. Org. Lett. 1999, 1,
681. (o) Arimoto, H.; Asano, S. Uemura, D. Tetrahedron Lett. 1999, 40,
3583. (p) Keen, S. P.; Weinreb, S. M. J. Org. Chem. 1998, 63, 6739.
(7) (a) Conley, R. T.; Annis, M. C. J. Org. Chem. 1962, 27, 1961. (b)
Ibuka, T.; Mitsui, Y.; Kayashi, K.; Minakata, H.; Inubushi, Y. Tetrahedron
Lett. 1981, 22, 4425. (c) Ibuka, T.; Minakata, H.; Mitsui, Y.; Hayashi, K.;
Taga, T.; Inubushi, Y. Chem. Pharm. Bull. 1982, 30, 2840.
(8) Hill, R. K.; Conley, R. T. J. Am. Chem. Soc. 1960, 82, 645.
(9) (a) Bird, C. W.; Naidoo, K. Synth. Commun. 1988, 18, 1119. (b)
Mellor, J. M.; Pathirana, R.; Stibbard, J. H. A. J. Chem. Soc., Perkin Trans.
1 1983, 2541.
(Table 1). In the presence of polyphosphate ester or poly-
phosphate silyl ester, the isomeric oximes underwent ste-
reospecific rearrangement to form (+)-8 and (+)-13, respec-
tively. The yields given by PPE were notably superior. Chiral
HPLC analysis demonstrated that the integrity of the ste-
reogenic center of the spirocyclic core was fully preserved
during the concerted 1,2-shift. In striking contrast, the use
of PPA as promoter resulted in the formation of (+)-13
(predominantly from (-)-9 or exclusively from (-)-12). This
departure from the norm is observed to a lesser extent with
Eaton’s reagent. These data provide decisive insight into the
fact that not all acidic Beckmann initiators are equivalent.
Polyphosphoric acid gives evidence of inducing the most
extensive departure from anti migration. No loss of optical
activity was evident for either product in entries 1-8.
Table 1. Acid-Promoted Beckmann Rearrangements of (-)-9
and (-)-12a
(10) Nieman, J. A.; Keay, B. A. Synth. Commun. 1999, 29, 3829.
(11) (a) Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277.
(b) Ireland, R. E.; Gleason, J. L.; Gegnas, L. D.; Highsmith, T. K. J. Org.
Chem. 1966, 61, 6856.
entry
keto oxime
promoter
lactam product(s)
yield,%
(12) (a) Nakazaki, M.; Chikamatsu, H.; Asao, M. J. Org. Chem. 1981,
46, 1147. (b) Harada, N.; Takada, K.; Uda, H. J. Chem. Soc. Chem.
Commun. 1977, 495. (c) Gerlach H. HelV. Chim. Acta 1968, 51, 1587.
(13) Racemic 8 has been reported previously, but with minimal
spectroscopic characterization: Evans, D. A.; Thomas, E. W.; Cherpeck,
R. E. J. Am. Chem. Soc. 1982, 104, 3695.
(14) Chemical intercorrelation was also achieved by transforming i
exclusively via its anti oxime to ii, followed by desilylation and oxidation
of this lactam:
1
2
3
4
5
6
7
8
(-)-9
(-)-12
(-)-9
(-)-12
(-)-9
(-)-12
(-)-9
PPA
PPA
Eaton
Eaton
PPE
PPE
PPSE
PPSE
(+)-8, (+)-13
(+)-13
(+)-8, (+)-13
(+)-8
(+)-8
(+)-13
4, 30
23
25, 8
20
70
70
(+)-8
(+)-13
19
34
(-)-12
a Product analysis was accomplished by analytical HPLC on a Chiralpak
AD column using either 25% or 60% ethanol in hexanes. The following
retention times were recorded; (+)-8, 12.8 min; (-)-8, 20.8 min; (+)-13,
12.7 min; (-)-13, 11.0 min. No racemization was operational in all eight
examples documented here.
(15) Horning, E. C.; Stromberg, V. L. J. Am. Chem. Soc. 1953, 74, 2680.
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