Rearrangement aminoalcohols

Carbocation rearrangement of (3-aminoalcohols via diazotization to afford carbonyl compounds through C-C bond migration. 

A syn displacement of the bromine by benzylamine in the presence of triethylamine led, by a Sn2 reaction, to the a and p amino compounds which were separated into 326 (18%) and 327 (81%) respectively. The dichloroacetamide 328 derived from the latter, when subjected to the action of tri-n-butyltinhydride (2eq) and 2,2 -azobisisobutyronitrile underwent a 5-ero ring closure to furnish via the radical 329, the hydrooxindole 330 (51%) and significant amount of the rearrangement product 331 (30%). The latter is believed to be formed by fragmentation of the cyclohexadienyl radical 332 generated from the cyclohexyl radical 329. On diborane reduction, 330 provided the cis hydroindole 333, which on 0,N-debenzylation afforded ( )-c -fused bicyclic aminoalcohol 334, a compound that had been previously cyclised with formaldehyde to ( )-elwesine (320) by Stevens et al [85]. 

Hydroxymethylaziridine 67 undergoes ring opening in the presence of either carbon- or heteroatom-based nucleophiles upon treatment with 2 equiv of potassium hydride to provide the t)7aminoalcohol derivative 69. The key step of the reaction is considered to be an aza-Payne rearrangement of the deprotonated aziridine methanol to the... 

The stereochemistry of cyclic primary amines or aminoalcohols dramatically influences the product distribution of their respective Demjanov and Tiffeneau-Demjanov rearrangements. P. Vogel and co-workers have studied the ring-expansion of 2-aminomethyl-7-oxabicyclo[2.2.1]heptane derivatives upon treatment with nitrous acid. Some of their findings are shown below. ... 

It should be noted that the 2-oxazolines are connected directly with enamides, being their products of cyclization on the one hand ", as well as being the heterocyclic precursors of W-acylenamines on the other . However, it is no less important that the 2-oxazolines are cyclic derivatives (and precursors also) of the 1,2-aminoalcohols. In essence, the reactions 117 122 (equation 41) and 125- 128 (equation 43) are the transformations of ketones to 1,2-aminoalcohols, i.e. they are the reversal of one of the pinacol rearrangement variants, i.e. the Tiffeneau and MacKenzie reactions . These transformations which proceed via the iV-acyliminium intermediates 118, 126 are examples of a real retropinacol rearrangement according to structural, functional and redox features (see Section III.B.3). 

Cationic rearrangement (ring enlargement) of 1,2-aminoalcohols by diazotization (see 1st edition). 

A more convenient procedure for the synthesis of (113) from (5) was later elaborated <9UOM(4l2)l>. It is based on the intramolecular version of the reaction of organoboranes with organic azides. The THF complex of 1-boraadamantane (5a) is treated with iodine in the presence of an excess of sodium azide. The iodine atom in the intermediately formed borabicycle (118) undergoes an easy nucleophilic substitution by azide ions. The subsequent anionotropic rearrangement in the borabicyclic azide (119) leads (after the oxidation of the reaction mixture) to aminoalcohol (120), which is smoothly converted to 1-azaadamantane (113). The yield of (113) in this synthesis is 40-45% based on (5a), or 20-22% based on triallylborane (Scheme 44). 

Any other reaction, such as deamination of a /3-aminoalcohol, that generates a carbonium ion of similar structure will normally be followed by a pinacol-type rearrangement. 

SchPTTip 1 S.21 r2.31-Meisenheimer rearrangement with an aminoalcohol-based chiral auxiliary. 

Somfai s group demonstrated the use of a Lil-promoted vinylaziridine-3-pyrroline rearrangement in the formal synthesis of the antibiotic (-)-anisontycia The commercially available 2-(4-methoxyphenyl)acetaldehyde 43 was subjected to Brown allylation followed by aminolysis of the resulting chlorohydrin to afford the enantioenriched aminoalcohol 44 f Scheme 11.34). The enantiopure cis-vinylaziridine 45 was then prepared by O- and N-tosylation of the chiral aminoalcohol followed by KOH-promoted ring closure. Microwave-assisted rearrangement of vinylaziridine 45 using Lil as an additive afforded enantioenriched 3-pyrroline 46 in excellent yield, and this was converted to the natural product in several steps tScheme 11.34T ... 

Linalool 54 was similarly synthesized through a [2,3]-Meisenheimer rearrangement by taking advantage of the facile cleavage of N—O bonds in the O-allylhydroxylamine rearrangement products (Scheme 15.111. Aminoalcohol 51 was converted to amine iV-oxide 52, which was transformed to O-allylhydroxylamine 53 under thermal conditions. This intermediate was subjected to reductive conditions, which selectively cleaved the N—O bond to unveil linalool 54. 

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