Intramolecular amidoalkylation

In the intramolecular amidoalkylation of certain (Z)-allylsilanes, piperidine derivatives (n = 2) are formed less stereoselectively than the corresponding pyrrolidines (n = 1). The complete regiocontrol is induced by the /3-effect of the silicon atom. 

The cycloaddition of alkynes and alkenes to nitrile oxides has been used in the synthesis of functionalised azepine systems <96JHC259>, <96T5739>. The concomitantly formed isoxazole (dihydroisoxazole) ring is cleaved by reduction in the usual way. Other routes to 1-benzazepines include intramolecular amidoalkylation <96SC2241> and intramolecular palladium-catalysed aryl amination and aryl amidation <96T7525>. Spiro-substituted 2-benzazepines have been prepared by phenolic oxidation (Scheme 5) <96JOC5857> and the same method has been applied to the synthesis of dibenzazepines <96CC1481>. 

Imidazo[2,l-fl]isoindolone 187 is the product of an intramolecular a-aza-amidoalkylation of N-acyliminium species 186. Nevertheless, when the jS-substituent is an aromatic moiety, a competing a-amidoalkylation takes place and isoindolo[l,4]benzodiazepine 188 is obtained under thermodynamic control (Scheme 37 (2004T11029)). 

Various methods are available for the preparation of the foregoing precursors to V-acyliminium ions. The most straightforward synthesis of V-(l-hydroxyalkyl)-amides or -carbamates (2 X = OH) involves the addition of primary or secondary amides (carbamates) to aldehydes or ketones. This reaction is an equilibrium process and usually disfavors the adduct except for two special cases. The first involves very reactive aldehydes like formaldehyde, chloral and glyoxylic acid and its esters (equation 4) compounds (4)-(6) are fairly stable compounds that are frequently used in amidoalkylation reactions. The second special case is the intramolecular variant (ring-chain tautomerism), if it leads to five- or six-membered rings (equations 5 and 6). Thus, for n = 1 or 2, (7) and (8) cyclize to (9) and (10), respectively, although the nature of R has an influence on this process. " ... 

Phthalimides and Related Compounds - 4-Amino-./V-methylphthalimide has been studied by laser flash photolysis. The photophysical parameters have been established by this approach and this study has supported the results obtained from steady state irradiations. Intramolecular photoelectron transfer photochemistry of the A-[(JV-acetyl-./V-trimethylsilyl-methyI)amidoalkyl]phthali-mides has been demonstrated. The yields obtained on irradiation in methanol range from low to medium. 

Vovk MV, Dorokhov VI, Bol but AV (1997) Intramolecular Amidoalkylation of N-Aryl-N -(l-aryl-2,2,2-trifluoroethylidene)ureas. Synthesis of 4-Aryl-4-trifluoromethyl-l,2,3,4-tetrahydroquinazolin-2-ones. Russ J Org Chem 33 1666-1668... 

Recently, Suh and coworkers have reported a new method of entry into functionalized cycloalkylamines via a diastereoselective intramolecular amidoalkylation of N, 0-acetal trimethylsilyl ether possessing allylsilane (104), under the effect of BF3 OEt2, to give the corresponding cyclic amine (105) in high diastereoselectivity (Equation 62) [61]. 

Kim et al. reported a diastereoselective intramolecular amidoalkylation of N,0-acetal trimethylsilyl (TMS) ethers possessing an allylsilane part in the presence of SnCU (Scheme 10.33) [58]. 

---