Stable bromoallene oxides †

The allene oxide functional group and its valence tautomeric cyclopropanone and oxyallyl cation forms are of significant interest. The first room-temperature stable allene oxide was reported in 1968 by peracid epoxidation of 1,3-di-tert-butylallene 1 to give epoxide 2.‡ 3 It was subsequently converted into its corresponding isomeric cyclopropanone 3 on heating thereby establishing their relative thermodynamic stabilities. However, despite this early success, only a handful of further allene oxides have been successfully characterised. Nevertheless, these studies have helped to establish that stable allene oxides can be obtained when (i) the epoxide is kinetically stabilised by steric protection against SN2 attack, and (ii) when cyclopropanone formation via the presumed intermediacy of an oxyallyl cation is non-favoured.

The allene oxide functional group and its valence tautomeric cyclopropanone and oxyallyl cation forms are of significant interest. 1,2The first room-temperature stable allene oxide was reported in 1968 by peracid epoxidation of 1,3-di-tert-butylallene 1 to give epoxide 2. ‡ 3 It was subsequently converted into its corresponding isomeric cyclopropanone 3 on heating thereby establishing their relative thermodynamic stabilities.][6][7][8][9][10] Nevertheless, these studies have helped to establish that stable allene oxides can be obtained when (i) the epoxide is kinetically stabilised by steric protection against S N 2 attack, and (ii) when cyclopropanone formation via the presumed intermediacy of an oxyallyl cation is non-favoured.1c We have recently reported 11 that DMDO epoxidation of 3-n-alkyl-1bromo-allenes 4 give rise directly to a,b-unsaturated carboxylic acids 5 by presumed spontaneous rearrangement of bromo-allene oxides -an unprecedented functional group in the literature 12 -to bromocyclopropanones and subsequent Favorskii rearrangement.
In that work, an analysis of the mechanism revealed that epoxidation of either olefin of the bromoallene would lead to the same product and so the site of initial epoxidation could not be identified.With the intention of identifying the preferred position of epoxidation in bromoallenes, we now report the first stable bromoallene oxides.
With the above literature precedents in mind, we selected known 1-bromo-1,3-di-tert-butylallene 6 -reported as a colourless liquidas a suitable substrate for epoxidation. 13However, in our hands it proved to be inseparable from its propargylic bromide isomer, was found to be somewhat volatile, and consequently epoxidation experiments proved inconclusive.Instead, we targeted novel adamantyl-containing bromoallenes 7-9, which proved to overcome these difficulties (vide infra).
Bromoallene 7 was prepared by the initial lithiation of terminal alkyne 10 and addition to adamantanecarboxaldehyde § to give propargylic alcohol 11 (Scheme 1).Temperature control in this transformation proved critical, otherwise significant quantities of ketone 12 and 1-adamantanemethanol were formed.¶8 Using the conditions of Corey, 13 alcohol 11 was transformed into bromoallene 7 along with the expected, but now separable, propargylic bromide 13.** Next, the action of the carbon tetrachloride-triphenylphosphine reagent combination 14 on adamantanecarboxaldehyde as a a,a,a-trisubstituted aldehyde provided ready access to vinyldichloride 14 15 free from any complicating dichloroalkane formation. 16Corey-Fuchs type acetylide anion formation, 17 and in situ trapping 18 with pivaldehyde and adamantanecarboxaldehyde gave propargylic alcohols 15 and 17 respectively in good yields.† † Bromoallenes 8 and 9 were subsequently obtained by subsequent reaction with thionyl bromide along with the corresponding expected, and again separable, propargylic bromides 16 and 18. ‡ ‡ The incorporation of adamantyl groupings rendered the three bromoallenes 7-9 to be solid, bromoallene 9 proved to be crystalline, and its structure was solved by X-ray crystallography.‡ § § With these compounds in hand, attention turned to epoxidation.¶ ¶ In the event, epoxidation of each of bromoallenes 7-9 with DMDO 19 provided monoepoxidation products as E-1-bromoallene oxides 19-2188 as single diastereoisomers respectively, along with bromodiketones 22-24,*** and recovered bromoallene starting materials after column chromatography (Scheme 2).† † † Importantly, under the conditions of the experiment and the isolation and purification regime, there was no evidence for the formation of any corresponding a,b-unsaturated carboxylic acids via intersecting bromoallene oxide-bromocyclopropanone-Favorskii rearrangement. 11These experiments therefore establish that (i) bromoallene oxides of this type are kinetically stabilised with respect to rearrangement by the bulky alkyl substituents; (ii) for these bromoallenes, epoxidation occurs preferentially at the bromine-bearing D 1,2 alkene and (iii) epoxidation occurs with complete face selectivity away from the alkyl grouping at C-3 of the allene.‡ ‡ ‡ Moreover, the uniformity of the product distributions obtained with the different bromoallenes 7-9 show that the tert-butyl and adamantyl groups behave as effectively identical and interchangeable substituents in this situation, but with the advantage that the incorporation of an adamantyl group increases the prospect of crystallinity.Indeed, bromoallene oxide 19 proved to be crystalline and its structure was determined by X-ray crystallography (Fig. 1).To the best of our knowledge this is the first X-ray crystallographic structural elucidation of any allene oxide.§ § § 20 We probed the origins of the observed regioselectivity and diastereoselectivity using DFT theory (oB97XD/TZVP,QZVP/C PCM = acetone as continuum solvent). 21An NBO analysis on representative reactant bromoallene 6 reveals the D 2,3 localized occupied p-orbital is higher in energy (by 0.014 Hartree) than the D 1,2 orbital, suggesting that the intrinsic electronic nucleophilic reactivity of the allene is at the 2,3 position.However, transition state models of the reaction with DMDO as electrophile reveals the 1,2 isomers are 1.2 (QZVP) or 1.4 (TZVP) kcal mol À1 lower in DG y 298 for bromoallene 6 and 1.2 (TZVP) for bromoallene 9.For the simplest possible bromoallene (H 2 CQCQCHBr, not shown) the 2,3 transition state at the p-face anti-periplanar to the Br is favoured by 0.4 kcal mol À1 over the 1,2 isomer and by 1.3 kcal mol À1 over 2,3-syn-periplanar attack (TZVP).Taken together, these calculations reveal that although the bromine atom is inherently deactivating for the D 1,2 olefin, it also acts to sterically protect the syn-periplanar face of the D 2,3 olefin.For bromoallenes 7-9, since the bulky alkyl group on C-1 protects the other face of D 2,3 olefin and the C-3 alkyl group inhibits Z-1-bromoallene oxide formation, D 1,2 attack leading to the E-1-bromoallene oxides 19-21 emerges as the most facile.
In conclusion, we have demonstrated that stable bromoallene oxides can be obtained by DMDO epoxidation of 1-bromo-1,3-di-tert-alkylallenes, and the first X-ray crystal structural elucidation of any allene oxide has thereby been accomplished.The epoxidation for these bromoallenes is selective for the bromine-bearing D 1,2 alkene, and with exclusive face selectivity to produce E-1-bromoallene oxides.¶ ¶ ¶ The thermal stability of these bromoallene oxides is the subject of current investigations and will be reported in due course.
We thank Mr Jaren Soo for preliminary investigations with compound 6.
Notes and references ‡ Interestingly, a definitive structure for allene oxide 2 was not given in the original report and two geometrical isomeric structures were proffered.Our results (vide infra) support this to be the E-allene oxide as drawn.§ Readily prepared from 1-adamantanemethanol by PCC oxidation.‡ ¶ See ESI † for experimental details.See also ref. 21.  8 We invoke an unprecedented irreversible hydride transfer from the initially formed secondary lithium alkoxide AdCH(CRC t Bu)OLi to still unreacted AdCHO in a concerted six-membered TS to explain this observation.In this process steric compression of the adamantylbearing sp 3 centre is relieved, and the formation of conjugated ynone 12 acts as a thermodynamic driving force.Formation of the lithium alkoxide from alcohol 11 by the action of n-BuLi, and subsequent addition of AdCHO gave also ynone 12.  ** 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 LiCuBr 2 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 RCH 2 OH.‡ ‡ 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 S N 2 0 reaction in which they are formed (ref.13).These structures are further supported by characteristic NOE enhancements and HMBC correlations.‡ ¶ ¶ At the outset, in a simplistic model, we predicted that epoxidation of a bromoallene would be electronically disfavoured at the D 2,3 alkene position due to the deactivating donation of its p-cloud into the periplanar C-Br s* orbital.However, was unclear whether the mesomeric activating release of a bromine lone pair into the D *** 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 cm À1 ; 23: 1719, 1690 cm À1 ; 24: 1717, 1692 cm À1 ), the presence of two carbonyl resonances in their 13 C NMR spectra (22: 206.3, 190.9 ppm; 23: 206.3, 191.0 ppm; 24: 205.9, 191.2 ppm), and a 13 C 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 R 0 ).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).
† † † 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 respectively, 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 oxides were observed.‡‡‡These results are also congruent with the reported epoxidations of tri(alkyl)substituted allenes (ref.4and10b) where (i) the most substituted 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-2016 update) for an allene oxide moiety returned only 3 hits, all of which are epoxyC60fullerenes.The O-C bond lengths in the epoxide moiety of bromoallene oxide 19 show a marked asymmetry.Whilst that to the sp 3 carbon [O1-C1 1.453(6) Å] is close to the average C-O bond length in epoxides with two sp 3 carbon centres [1.446 Å], that to the sp 2 carbon of the adjacent CQC double bond is significantly shorter [O1-C2 1.388(7) Å].The C-C bond of the epoxide moiety [C1-C2 1.435(8) Å] is also shorter than the average for epoxides with two sp 3 carbon centres [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 of CQC double bonds in allene units, and in epoxides with two sp 3 carbon centres came from statistical analyses of searches of the Cambridge Structural Database).¶ ¶ ¶ The question of the preferred site of epoxidation in 1-bromo-3-alkyl allenes (ref.11) remains experimentally unresolved however.