Regioselective Reductive Ring Opening of 2‐(2‐Hydroxyphenyl)‐3‐[(trimethylsilyl)oxy]oxetanes at the More Substituted C‐2 Position

Abstract

The title compounds 7 were prepared in situ by deprotection of the corresponding pivaloyl-substituted oxetanes 3 with lithium aluminium hydride in tetrahydrofuran. Under these conditions a reductive ring opening at C-2 (hydrodealkoxylation) occurred which was initiated by a nucleophilic hydride attack and which yielded the triols 8 (64-85%). The facility of the reaction and its high regioselectivity can be explained by the directing ability of the hydroxy group at the aromatic substituent. The reaction proceeds stereospecifically, as shown by deuterium labelling experiments. The prerequisite 2-(2-pivaloyloxyphenyl) -3 -[ (trimethylsilyl)oxy]oxetanes 3 were prepared by the Paterno-Biichi reaction of the protected salicylaldehyde 1 and various silyl enol ethers 2. The 2-hydroxyphenyl substituent at the C-3 position of oxetane 6 directed the hydride attack to the C-4 position and yielded the trio1 10 in 85% yield.2-aryloxetanes are readily available since the [2 + 21-photocycloaddition of aromatic aldehydes to various alkenes has been shown to proceed cleanly and in good yields [']. Most transformations which employ these compounds for regioselective ring opening reactions at the aryl-substituted carbon atom C-2 make use of the fact that a positive charge at C-2 is stabilized by the adjacent arylIn the initial step, Lewis or Bronsted acids coordinate to the ring oxygen atom and activate the oxygen-carbon bond which is eventually to be broken. The subsequent nucleophilic attack occurs at C-2, mostly by an SNl-type mechanism. Alternative routes for a regioselective ring opening at the C-2 position of 2-aryloxetanes include reductive metalation with aromatic radical anions[3], transition-metal-catalyzed carbonylati~n [~I, methylenation['], and catalytic hydrogenolysisr6]. We became interested in possible ways of opening the ring in 2-aryl-3-silyloxyoxetanes at the more substituted C-2 position in connection with our studies on the Paterno-Buchi reaction of silyl enol ethers and aromatic aldehydesr']. We realized quickly, however, that the acidic conditions which are necessary for many regioselective ring openings (vide infra) are not compatible with the silyloxy group at C-3. Upon attempted activation of the carbon-oxygen bond, a pinacol-type rearrangement occurs yielding a-hydroxy ketones [s]. A possible remedy to avoid the alkyl shift appeared to be a nucleophilic substitution reaction which was to be directed to the desired C-2 posi- To this end, 2-(2-hydroxyphenyl)-substituted oxetanes were chosen as promising candidates. The hydroxy group was considered to be an effective device for the precomplexation of a metal ion M which in turn may deliver the nucleophile NuL91. The following account, in which the hydride ion is the nucleophile of choice, describes the results of our synthetic efforts in this areal'"].

Photocycloaddition of N-Acyl Enamines to Aldehydes and Its Application to the Synthesis of Diastereomerically Pure 1,2-Amino Alcohols

“…The parent 3-oxetanols, however, do undergo these reactions with ease . It was postulated that the free hydroxy group in these oxetanes is able to coordinate the metal that carries the potential nucleophile, thus rendering the reaction intramolecular. , If similar arguments were applicable to 3-aminooxetanes, the secondary 3-oxetanylamides 5a and 5b should be amenable to nucleophilic substitution at C-4. Indeed, the formamide 5a readily reacted with LiAlH 4 to yield a ring-opened product that was identified as pseudoephedrine ( 8 ) by comparison with authentic material (Scheme ).…”

Stereoselective Intermolecular [2 + 2]-Photocycloaddition Reactions and Their Application in Synthesis

“…221 If a polar group is situ-ated on one of the former substituents of the carbonyl compound it may direct a nucleophilic attack to the higher substituted position and thus facilitate a ring-opening according to path a. 222 The preeminent importance of the furan photocycloaddition (cf. Scheme 38) for stereoselective synthesis rests in part on the facile ring opening of its products according to path b.…”

Synthesis of Three‐Membered and Four‐Membered Heterocycles with the Assistance of Photochemical Reactions

“…This example showed the formation of oxetanes by photochemical cycloaddition of carbonyl compounds to olefins (Scheme ).…”

“…However, under the same conditions, Jerry Gao found that several cycloadducts were formed upon irradiation of methylstyrene and benzaldehyde (Scheme 40). This example showed the formation of oxetanes by photochemical cycloaddition of carbonyl compounds to olefins [168][169][170][171][172][173][174][175][176]…”