Cydic imines

Molgo, (., Girard, E., and Benoit, E. (2007) Cydic imines an insight into this emerging group of bioactive marine toxins, in Phycotoxins Chemistry and Biochemistry (ed. LM. Botana), Blackwell Publishing, Oxford, pp. 319-335. 

The CROP of 2-oxazolines was first reported in 1966 by four independent research groups [62-65]. The major advantage of the 2-oxazoline polymerization, compared to cationic cyclic ether polymerizations, is the large difference in nudeophihcity of the cydic imine of the 2-oxazoline monomer and the amide of the ring-opened... 

Reactions with seven- to nine-membered cydic allylic carbonates or halides give the corresponding cydic allyltitanium compounds. These reagents add to aldehydes and imines with moderate to excellent diastereoselectivities [59]. The allyltitanium compound generated from 1-vinylcyclopropyl carbonate reacts regioselectively with aldehydes and ketones at the less substituted carbon atom to provide alkylidenecydopropane derivatives, as shown in Scheme 13.29 [60], The regiochemical outcome of the reaction can be rationalized by assuming an equilibrium between two allyltitanium spedes that favors the less strained tertiary structure. 

Intramolecular nucleophilic displacements are sometimes better suited to difficult cyclizations than additions to C-C multiple bonds, because nucleophilic substitutions are usually irreversible. Some metalated 4-halobutyl imines cydize to yield cydobutanes rather than six-membered cydic enamines (Scheme 9.22). If alkoxides are used as bases, however, exclusive N-alkylation is observed. No examples could be found of the cydization of 4-halobutyl ketones to cyclobutyl ketones, but 5-halopen-... 

It is of some interest to speculate briefly oonocmiug the nature iH the peradd-imine reaction. It is quite possible that this reactkMi is analogous to the epoxidatkm olefins with peracids and involves a similar cydic transition state (X). An equally attractive if less obvious possibility is that the imine reaction proceeds throu additioti of t-ho pcracid to the azometlune followed by internal nucleophilic displace ment the haaic nitrogen atom on the peroxide bond. This reaction... 

A similar concept was applied to the two-component synthesis of indoles 164 via cydoisomerization of alkynyl imines 162 (Scheme 9.61) [220]. N-(Alkoxymethyl) indoles 164 were readily prepared through the Cu(I)-catalyzed cyclization-hydroxyla-tion reaction of the imine precursors 162 in the presence of a variety of external O-nucleophiles 163, such as alcohols and phenols, with good functional group compatibility. The authors believe that this domino reaction begins with the Cu( I)-activation of alkyne 162 toward 5-ewdo-digcyclization to form a cydic metal-containing azomethine... 

---