Sterically Congested Molecules, 17. – Novel Syntheses of α,α,β‐Tri‐tert‐butyl Compounds

Abstract

Pivaloin (2), prepared from ethyl pivalate (1) or from dimethyl oxalate (3), reacts with tert-butyllithium by reduction (45% of 10) and addition (45 % of 9), whereas the corresponding Barbier variant takes a different course. Productive transformations of the a,a,P-tri-tert-butyl glycol 9 lead to a,p,p-tritert-butylethanone (17, overall 4 steps), or a,a,P-tri-tert-butyl-ethene (20, 3 or 4 steps), or a,p,P-tri-tert-butyl-P-hydroxyethanone (19, 3 steps, also by Grignard addition to bipivaloyl 4). Steric congestion is assessed by searches for restricted internal rotation.. The alkene 20 and its epoxide 27 are studied with respect to NMR assignments and chemical degradation.We describe short routes to several a,a,P-tri-tert-butyl compounds which are either new or have been previously prepared only by long or inefficient procedures. Some of their properties are reported to show how intramolecular mobility and chemical reactivity may depend on the overcrowding caused by three tert-butyl ("tBu") groups. A. Preparation and teut-Butylation of PivaloinPivaloin (2) is the common source of all material described in this work but is commercially no longer avail-abler2]. For its preparation from ethyl pivalate (1) and sodium metal, the leading references"] are rather laconic and do not mention the considerable amount (ca. 2.50/) of yellow bipivaloyl (4) generated in the process. We preferred to run this acyloin condensation on large scales in to provide for an easier separation of 4r41 and purification of 2 that yielded at least 52% of colourless pivaloin, with the 'H NMR doublet splitting typical"] of the very clean material. Diketone 4 was certainly formed by a protolytic disproportionation of its radical anion that would have either been present as one of the primary products or perhaps resulted from rapid oxidation[6] of the expectedr71 enediolate 5. Trapping of 5 with chlorotrimethylsilane did not appear yield. 4 Na i 25% o be helpful in view of a much lower reported[7]> 52%

Pivaloylmetals (tBu‐COM: M=Li, MgX, K) as Equilibrium Components

“…Pivaloylmagnesium : The deprotonation (Scheme ) of tri‐ tert ‐butylacyloin8–10 ( 1 ) by ( tert ‐butyl‐ or) methylmagnesium chloride in tetrahydrofuran (THF) produced two structurally undefined Mg alkoxides 5 (detected through 1 H NMR spectroscopy in situ) which approached their equilibrium ratio (ca. 75:25) with a first half‐life time ( t 1/2 ) of roughly 8 min at room temperature 11.…”

“…Pivaloyllithium : Two structurally undefined Li alkoxides 14 (population ratio ca. 20:80 by 1 H NMR in situ) resulted from deprotonation (Scheme ) of tri‐ tert ‐butyl acyloin8, 9, 10 ( 1 ) in THF by methyllithium, whereas only one kind of Li alkoxide 14 was formed from 1 in hydrocarbon solution with n ‐butyllithium ( n BuLi) 11. The cleavage of these alkoxides (“fission” in Scheme ) will generate pivaloyllithium7 ( 13 ) or its complex 13 & 7 with O=C t Bu 2 ( 7 ).…”

Deuterium Quantification through Deuterium‐Induced Remote1H and13C NMR Shifts

“…4‐ tert ‐Butyl‐4‐hydroxy‐2,2,5,5‐tetramethylhexan‐3‐one (“Parent” acyloin) : 1 H and 13 C NMR data can be found in Ref. 24.…”