Oximes, mesylation

Organoaluminum-promoted Beckmann rearrangement/methylation of cyclohexanone oxime mesylate, followed by allylation of ketimine 40a and Mannich cyclization of the intermediate iminium-allylsilane, provides piperidine 40b possessing cxo-unsaturation (08BKC1669). 

In many of these cases, the nucleophile is a C=C double bond (usually an alkenic group and less frequently an aromatic group). Alkenic oxime mesylates enable intramolecular cyclization by an electrophihc addition of the double bond to the electrophilic intermediate. These reactions are terminated by a proton loss. 

Another synthetic route via the Beckmann rearrangement, which is promoted by organoaluminum reagent along with alkylation, involves a new stereoselective reduction of the imino group. The starting oxime sulfonate (228) was synthesized from cyclopentanone (226) in three steps Reaction of 226 with 1-undecene in the presence of silver oxide produced the a-undecylcyclopentanone (227) which on successive treatment with hydroxylamine and methanesulfonyl chlo-ride-triethylamine gave the mesylate (228). Treatment of the oxime mesylate... 

The benzenesulfonate of cycloheptanone oxime rearranges readily at room temperature to give the very electrophilic O- benzenesulfonate (7), which reacts with pyridine to give the salt (8) (67CB3024). Treatment of (8) with water gives (2), and with H2S the thione (9) is produced (58CB972). The reaction of aluminum alkyls with cycloheptanone oxime mesylate provides a direct route to 2-alkyl-substituted octahydroazocines (81JA7368). 

Imidoyl iodides. Reaction of oxime mesylates (or carbonates) of ketones with (C2H5)2A11 effects Beckmann rearrangement to imidoyl iodides, which can be directly alkylated with Grignard reagents and then reduced (DIBAH) to a-alkylated amines. Examples ... 

Enaminones. Coupling of enol silyl ethers with oxime mesylates can be effected via a Beckmann rearrangement with diethylaluminum chloride. 

For example, treatment of oxime mesylate (191) with MesAl (2 equiv.) in CH2CI2 (-78 °C) followed by allylmagnesium bromide (2 equiv., -78 to 0 C) yields amine (192 equation 23). ... 

The isolable imine (39), which is obtainable by the rearrangement of 2-undecylcyclopentanone oxime mesylate with MesAl, can be transformed to either the cis or trans isomer with high stereoselectivity depending on the choice of the reducing agents (Scheme 3). Reduction of (39) with MesAl-LiAlHt completes a short synthesis of solenopsin A (40). ... 

Trapping of the Beckmann intermediates with enol silyl ethers affords facile entry to a variety of en-amino ketones. This condensation takes place with retention of regiochemical integrity in both oxime sulfonates and enol silyl ethers. Reaction of 6-methyl-l-(trimethylsiloxy)-l-cyclohexene (41) or 1-methyl-2-(trimethylsiloxy)-l-cyclohexene (42) with cyclohexanone oxime mesylate furnishes (43) or (44), respectively, as the sole isolable products (equation 25). Another striking feature of the reaction is the high chemospecificity. The condensation of the enol silyl ether (45), derived from p-acetoxyaceto-phenone, occurs in a chemospecific fashion with cyclododecanone oxime mesylate, the acetoxy moiety remaining intact (equation 26). Oxime sulfonates of aromatic ketones and cyclopentanones are not employable since complex reaction mixtures are formed. 

The efficient activation of oxime sulfonates by organoaluminum reagents enables the intramolecular cyclization of alkenic oxime mesylates, which involves the electrophilic addition of the intermediate ni-trilium ion to the double bond. This results in the direct formation of a wide variety of structurally diverse carbocyclic and heterocyclic systems. Four distinct cyclization modes, i.e. endo(B)-endo, endo(B)-exo, exo(B)-endo and exo(B)-exo are possible, as shown in Scheme 4P The values in parentheses refer to the yields obtained using SnCU. 

The alkenic cyclizations described above are terminated by deprotonation, yielding unsaturated im-ines. The intermediate carbocations, however, may also be captured by carbon nucleophiles to afford saturated imines. For example, treatment of the oxime mesylate (47) with Me Al followed by reduction with DIB AH predominantly produces the methylated product (48 equation 31). ... 

The Beckmann rearrangement of oxime mesylates initiated by TiCU has been applied to the preparation of 1,2-dehydro-1-aminoalkylphosphonates, e.g. 201, through trapping of the intermediate with triethyl phosphite. Oximes of a-ketophosphonates are often difficult to reduce to the corresponding 1-aminoalk-... 

In summary, the known preparative methods for the synthesis of [l,2,3]triazolo[l,5-a]pyridines prior to 1983 have been extensively reviewed in a number of different reviews <61CHE749,83AHC(34)80, 84CHEC-I(5)847>. These reviews reveal that the most straightforward methods involves an oxidation of the hydrazone of a pyridine-2-carbaldehyde or ketone, treatment of a tosylhydrazone with a base, cyclization of Af-aminopyridinium oxime mesylates, pyrolysis of pyridyldiazoalkanes, and diazo group (tosyl azide as source of the diazo group) transfer to an active methylene group (e.g., 2-methylpyridines) under basic conditions. 

The Beckmann rearrangement of 2-methoxy-5/f-benzo[a]cyclo-hepten-5-one oxime mesylate (51) in the presence of ArMgBr in dry toluene afforded 8-methoxy-2-phenyl-l-benzazocine (52). ... 

Ketone 57 upon reaction with hydroxylamine hydrochloride and subsequently with MeS02Cl afforded the oxime mesylate isomers 58 and 59, respectively. These mesylates separately underwent the Beckmann rearrangement in the presence of KH2PO4 in THF affording the tricyclic amides 60 and 61, respectively. ... 

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