Facile Synthesis of Various 1-Azabicyclo[n.4.0]alkanes via Beckmann Rearrangement/Allylsilane Cyclization

Abstract

The carbon-carbon bond formation by the reaction of allylsilanes with electrophiles has been widely used in organic synthesis.1 Particulary, intramolecular cyclization of allysilanes bearing an electrophilic terminus has an extensive application for the highly regio-and stereo-selective synthesis of various ring compounds.The bismetallic reagent 3-stannyl-2-(silylmethyl)propene 1 2 should be a versatile conjunctive reagent since the allylstannane and the allylsilane moieties of 1 could be manipulated sequentially and in a controlled manner.3 Indeed, the allylstannane moiety of 1 selectively react with an aldehyde to yield hydroxy allylsilane 2. 4 The reactions of 2 with either vinyl ethers or α-halo ethers give acetals which are subsequently cyclized to afford 2,6-cis-disubstituted-4-methylenetetrahydropyrans 3. 5Enantioselective synthesis of the tetrahydropyrans 3 was achieved by using the hydroxy allylsilanses 2 generated from the catalytic asymmetric allylation of 1 with aldehydes. 6 This annulation reaction enabled an efficient synthesis of the biologically active tetrahydropyran natural products.7 Various 2,6-disubstituted 4-methylenepiperidines were also prepared in one-pot by the sequential reactions of aldimines with bismetallic reagent 1 followed by aldehydes. 8 We described herein the synthesis of 1-azabicyclo[n.4.0]-alkanes using bismetallic reagent 1. Reaction of α-tetralone oxime mesylate 6a with 2 equivalents of trimethylaluminum resulted in the formation of cyclic ketimine 8a. Methylation of intermediate iminocarbocation 7a, which was generated from the organoaluminum-promoted Beckmann rearrangement 9 of oxime mesylate 6a, with trimethylaluminum afforded cyclic imine 8a. Allylation of cyclic ketimine 8a with allyllithium 9 gave cyclic amino allylsilane 10a in good yield.10 2-(Trimethylsilylmethyl)allyllithium 9 was generated by treating bismetallic reagent 1 with methyllithium.This easy and one-pot reaction has a wide generality. Other synthetic examples of this type are given in Table 1. It permits the introduction of an allylsilane moiety into a substrate with a simultaneous ring expansion.In the synthesis of ketimines 10a and 10b, rigorous regioselectivities were observed. The phenyl group anti to departing mesylate group migrated preferentially. 9 For some reasons, this process did not work for all the oxime mesylated tested. For example, reaction of 1-indanone oxime mesylate 6i with trimethylaluminum and followed allyllithium 9 under standard reaction condition gave only diallylation product 11 in low yield.11 Even with larger excess of trimethylaluminum (4 equiv) and after prolonged reaction time, the expected monoallylation product 10i was not produced. It is not clear why such anormalous behavior was observed for 1-indanone oxime mesylate only.Mannich cyclization of iminium-vinyl and allylsilanes is to provide an attractive method for the regio-controlled production of piperidines possessing either endo-or exo- 1670 Bull. Korean Chem. Soc. 2008 Communications to the Editor cyclic unsa...

An Interrupted Schmidt Reaction: C–C Bond Formation Arising from Nitrilium Ion Capture

“…In the intervening decades, very few examples of intercepting the nitrilium ion with other oxygen or nitrogenbut not carbonnucleophiles have been noted . In contrast, similar intermediates obtained through the Beckmann rearrangement of oximes are known to react with allylsilanes, organometallics, and other reagents . Such “interrupted” reactions, a class that also includes Nazarov, Pummerer, Fischer, and Bischler–Napieralski variations, enhance synthetic efficiency by combining multiple bond formations in a single step.…”