Aminochlorination intramolecular

An intramolecular version offers useful synthetic methods for heterocycles. The total syntheses of a- and 7-lycoranes (373 and 374) have been carried out by applying the intramolecular aminochlorination of the carbamate of 5-(2-aminoethyl)-l,3-cyclohexadiene (372) as a key reaction[312,313]. Interestingly, the 4,6- and 5,7-diene amides 375 and 377 undergo the intramolecular amina-tion twice via x-allylpalladium to form alkaloid skeletons ofpyrrolizidine (376) and indolizidine (378), showing that amide group is reactive[314]. 

In another reaction, in the presence of TMSCl and FeCla catalyst, decomposition of propargyloxycarbonyl azide results in the formation of an intramolecular syn-aminochlorination product under mild conditions (eq 58). ... 

Michael recently described aminochlorination reactions from intramolecular aminopalladation follotved by reaction tvith N-chlorosuccinamide (NCS) [17]. Initial reactions made use of Michael s earlier observation on stabilization of aminopallada-tion intermediates starting from 5 mol% ligated Pd complex A [18], but further tvork shotved that simple palladium salts such as Pd(NCMe)2Cl2 could also be employed, albeit in higher catalyst loadings of 10 mol% (Eq. (4.7)). The reaction tvorks well for a series of amides and carbamates, but not for tosylates. 

Michael used a sequence of nucleopalladation followed by chlorination with N-chlorosucdnimide (NCS) as an alternative protocol for intramolecular aminochlorination. This protocol works with excellent selectivity, providing pyrrolidine formation from a metal-free chlorine source. In contrast, a cyclization attempt to a six-membered product led to product mixtures including a 3-chloro azepin. Azepin was the only product that was produced using N-bromosuccinimide (NBS)... 

A direct synthesis of these aminochlorination products was developed by Liu et al. [85], who reported a highly regio- and diastereoselective intramolecular aminochlorination of unactivated alkenes 122 to arrive at substituted piperidines 123 (Scheme 16.30). This reaction is synthetically interesting because it uses hydrogen... 

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