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** Unwanted bromide 13 was found to slowly isomerise to bromoallene
7 on standing as a neat liquid, or this could be induced by the action
of LiCuBr2 in refluxing THF. As a representative experiment, after 20 h
at reflux, allene 7 and bromide 13 were obtained as a 1.35 : 1 mixture
respectively.
†† Temperature control was found to be essential to prevent hydride
transfer to give products of the type RCOCRCAd and RCH2OH.
‡‡ Bromides 16 and 18 also isomerised on standing (tlc analysis) into
their respective bromoallenes.
§§ The regioisomeric structures of bromoallenes 7 and 8 follow by the
nature of the SN20 reaction in which they are formed (ref. 13). These
structures are further supported by characteristic NOE enhancements
and HMBC correlations.‡
1 For reviews see: (a) G. L’abbe, Angew. Chem., Int. Ed. Engl., 1980, 19,
276–289; (b) W. Smadja, Chem. Rev., 1983, 83, 263–320;
(c) T. H. Chan and B. S. Ong, Tetrahedron, 1980, 36, 2269–2289.
2 For computational studies see: B. A. Hess, Jr., U. Eckart and
J. Fabian, J. Am. Chem. Soc., 1998, 120, 12310–12315 and references
cited therein.
3 (a) R. L. Camp and F. D. Greene, J. Am. Chem. Soc., 1968, 90, 7349.
A contemporaneous report on the peracid epoxidation of isomeric
1,1-di-tert-butylallene showed that 2,2-di-tert-butylcyclopropanone
was formed instead: (b) J. K. Crandall and W. H. Machleder, J. Am.
Chem. Soc., 1968, 90, 7347–7349. 1,1-Di-tert-butylallene oxide
was later characterised in solution after low temperature epoxidation
(ref. 4).
¶¶ At the outset, in a simplistic model, we predicted that epoxidation of
a bromoallene would be electronically disfavoured at the D2,3 alkene
position due to the deactivating donation of its p-cloud into the
periplanar C–Br s* orbital. However, it was unclear whether the
mesomeric activating release of a bromine lone pair into the D1,2 alkene
would overcome its inductive deactivating effect.
88 The bromoallene oxides 19–21 showed characteristic allene oxide
vinyl resonances in their 1H NMR spectra (CDCl3) at 4.84, 4.97 and 4.83
ppm respectively allowing immediate identification of regiochemistry
of epoxidation. Their respective 13C NMR resonances (CDCl3) at C-3
(100.2, 100.3, 100.4 ppm) match perfectly with an allene oxide of the
type tBuCHQC–(–O–)CHR (100.3 ppm, ref. 6). Characteristic IR
stretchesꢀfor all bromides 19–21 at 1806 cmꢀ1 show them to be allene
oxides (see ref. 1c).
4 1,1,3-Tri-tert-butylallene oxide reported as a 10 : 1 mixture with
an oxetane by glpc, and 1,3-di-tert-butyl-1-methylallene oxide
as the major component of a four component mixture: J. K.
Crandall, W. W. Conover, J. B. Komin and W. H. Machleder, J. Org.
Chem., 1974, 39, 1723–1729. These trisubstituted allene oxides
were reported to be resistant to conversion to their isomeric
cyclopropanones.
5 1-tert-Butylallene oxide as a ‘reasonably pure compound’ by reduced
pressure bulb-to-bulb distillation: (a) T. H. Chan and B. S. Ong,
J. Org. Chem., 1978, 53, 2994–3001 and references cited therein. This
allene oxide was reported to polymerise on standing in solution.
This allene oxide has been prepared as a single enantiomer:
(b) T. Konoike, T. Hayashi and Y. Araki, Tetrahedron: Asymmetry,
1994, 5, 1559–1566.
*** We invoke the formation of bromodiketones 22–24 via further
epoxidation of bromoallene oxides 19–21 to give their respective
bromospirodiepoxides, followed by ring-opening rearrangement to
the diketones with bromide anion loss from C-1 and gain at C-3 (for
the ring-opening rearrangement of spirodiepoxides of trisubstituted
allenes with halide anions see ref. 10b). They were assigned these
structures on the basis of their characteristic diketone stretches in
their IR spectra (22: 1713, 1694 cmꢀ1; 23: 1719, 1690 cmꢀ1; 24: 1717,
1692 cmꢀ1), the presence of two carbonyl resonances in their 13C NMR
spectra (22: 206.3, 190.9 ppm; 23: 206.3, 191.0 ppm; 24: 205.9,
191.2 ppm), and a 13C NMR resonance at ca. 59 ppm (22: 58.8 ppm;
23: 58.2 ppm; 24: 59.1 ppm) that displays a bromine induced isotopic
shift (for 22, Dd = 1.6 ppb).‡ NOEs from H - R (22, NOESY; 23, 4.58%)
confirm the bromide has shifted rather than a possible hydride shift
(interchanging R and R0). However, their expected molecular ions with
the characteristic bromine isotope pattern could not be observed by
mass spectrometry, and only m/z 135 (Ad+) was observed by EI+ or CI+
methods (for 23, 24).
6 For a stable 3-tert-butylallene oxide from a fulvene endo-peroxide
isolated by preparative tlc see: I. Erden, J. Drummond, R. Alstad and
F. Xu, Tetrahedron Lett., 1993, 34, 1255–1258.
7 Some non tert-butylallene oxides could be generated photo-
chemically and detected by 1H NMR methods in solution:
(a) L. E. Breen, N. P. Schepp and C.-H. E. Tan, Can. J. Chem.,
2005, 83, 1347–1351. See also: (b) M. D. Clay, J. Durber and
N. P. Schepp, Org. Lett., 2001, 3, 3883–3886; (c) M. W. Konecny
and N. P. Schepp, Org. Biomol. Chem., 2009, 7, 4437–4443 and
references cited therein.
8 For the isolation and characterization of a natural allene oxide as an
unstable intermediate in the metabolism of lipid hydroperoxides
see: (a) A. R. Brash, S. W. Baertschi, C. D. Ingram and T. M. Harris,
Proc. Natl. Acad. Sci. U. S. A., 1988, 85, 3382–3386 and references
cited therein. For E vs. Z isomers see: (b) A. R. Brash, W. E. Boeglin,
D. F. Stec, M. Voehler, C. Schneider and J. K. Cha, J. Biol. Chem.,
2013, 288, 20797–20806. See also: (c) N. V. Medvedeva, S. K. Latypov,
A. A. Balandina, L. S. Mukhtarova and A. N. Grechkin, Russ. J. Bioorg.
Chem., 2005, 31, 595–596.
9 For representative use of allene oxides as intended transient inter-
mediates see: (a) M. Shipman, H. R. Thorpe and I. R. Clemens,
Tetrahedron, 1998, 54, 14265–14282; (b) I. R. Clemens, M. Shipman
and H. R. Thorpe, Synlett, 1995, 1065–1066; (c) S. J. Kim and
J. K. Cha, Tetrahedron Lett., 1988, 29, 5613–5616 and references
cited therein.
††† The yields represent the optimized yields for the bromoallene
oxides using 3.0 equivalents of DMDO where the total mass recoveries
from these experiments are 490%. The use of 1.5 equivalents gave the
bromoallene oxides 19–21 in 21%, 19% and 21% isolated yield respec-
tively, with (for 7 and 8) 8% and 6% of 22 and 23, and recovered starting
materials 7 (68%) and 8 (74%) for 495% total mass recovery. The use of
5.0 equivalents (for 7 and 8) led instead to the predominant formation
of the corresponding bromodiketones 22 and 23 where no bromoallene 10 For the first report of a stable spirodiepoxide (from bisepoxidation
oxides were observed.
of allenes) see: (a) J. K. Crandall, W. H. Machleder and M. J. Thomas,
J. Am. Chem. Soc., 1968, 90, 7346–7347. For a recent representative
use of spirodiepoxides in cascade reactions see: (b) R. Sharma,
M. Manpadi, Y. Zhang, H. Kim, N. G. Ahkmedov and L. J. Williams,
Org. Lett., 2011, 13, 3352–3355.
‡‡‡ These results are also congruent with the reported epoxidations of
tri(alkyl)substituted allenes (ref. 4 and 10b) where (i) the most sub-
stituted alkene is epoxidised, and (ii) the epoxidation occurs with face
selectivity for the resulting E-olefin.
§§§ A search of the Cambridge Structural Database (version 5.37, Feb- 11 D. C. Braddock, J. Clarke and H. S. Rzepa, Chem. Commun., 2013, 49,
2016 update) for an allene oxide moiety returned only 3 hits, all of 11176–11178.
which are epoxyC60fullerenes. The O–C bond lengths in the epoxide 12 Ethyl 2-bromo-3-(diphenylmethylene) oxirane-2-carboxylate (i.e., a
moiety of bromoallene oxide 19 show a marked asymmetry. Whilst that
to the sp3 carbon [O1–C1 1.453(6) Å] is close to the average C–O bond
length in epoxides with two sp3 carbon centres [1.446 Å], that to the sp2
bromoallene oxide ester) was reported in a study of ketenes and
aliphatic diazo compounds: H. Staudinger and T. Reber, Helv. Chim.
Acta, 1921, 4, 3–23.
carbon of the adjacent CQC double bond is significantly shorter [O1–C2 13 E. J. Corey and N. W. Boaz, Tetrahedron Lett., 1984, 25, 3055–3058.
1.388(7) Å]. The C–C bond of the epoxide moiety [C1–C2 1.435(8) Å] is 14 R. Appel, Angew. Chem., Int. Ed., 1975, 14, 801–811.
also shorter than the average for epoxides with two sp3 carbon centres 15 This useful building block has only been reported once previously
[1.467 Å]. The C2–C3 double bond [1.304(8) Å] is unchanged from the
average seen in allene systems [1.317 Å] (data for average bond lengths
(by a different method): J. Buendia, B. Darses and P. Dauban, Angew.
Chem., Int. Ed., 2015, 54, 5697–5701.
of CQC double bonds in allene units, and in epoxides with two sp3 carbon 16 The CCl4–PPh3 combination on aldehydes typically gives rise to
centres came from statistical analyses of searches of the Cambridge
Structural Database).
dichloromethane and dichloroalkene mixtures: R. Rabinowitz and
R. Marcus, J. Am. Chem. Soc., 1962, 84, 1312–1313.
¶¶¶ The question of the preferred site of epoxidation in 1-bromo-3-alkyl 17 There are surprisingly only limited literature precedents for the
allenes (ref. 11) remains experimentally unresolved however.
alkyl lithium mediated conversion of 1,1-dichloroalkenes into
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Chem. Commun.