Stereoselective syntheses of (+)- isoretronecanol and (+)-5-epi-tashiromine via addition of chiral titanium (iv) enolates to cyclic n-acyliminium ions

Abstract

Recebido em 4/1/08; aceito em 14/3/08; publicado na web em 9/4/08The stereoselective addition of the titanium (IV) enolates derived from (S)-4-isopropyl-N-4-chlorobutyryl-1,3-thiazolidine-2-thione (8) and from (S)-4-isopropyl-N-4-chloropentanoyl-1,3-thiazolidine-2-thione (9) to N-Boc-2-methoxypyrrolidine (5b) afforded the addition products (+)-10 and (+)-11 in 84% yield in both cases, as 8.6:1 and 10:1 diastereoisomeric mixtures, respectively. A threestep sequence allowed to convert these adducts to (+)-isoretronecanol (1) and (+)-5-epi-tashiromine (2) in 43% and 49% overall yield, respectively.

Scaffold Diversity from N-Acyliminium Ions

“…69 Starting from acyclic precursors, Dobbs and co-workers reported the synthesis of analogous bicyclic [6,5] and [6,6] aza scaffolds relying on aza-Prins and aza-silyl-Prins reactions with concomitant incorporation of halo, phenyl, and amido substituents. Substrates 27a and 27b, containing both amide and aldehyde functional groups, the latter masked with an acetal protecting group, underwent intramolecular NAI formation and subsequent aza-Prins (28) or aza-silyl-Prins cyclization (29). Iron chloride, indium trichloride, and indium tribromide were used as Lewis acids to promote the double cyclization process (Scheme 10).…”

“…NAI chemistry has also been widely applied for the functionalization of monocyclic pyrrolidines and piperidines at the α-position; − however, reactions used for the introduction of substituents on monocyclic scaffolds are also outside the scope of this review. It must be mentioned that a plethora of intermolecular NAI reactions, typically deriving from hydroxylactams or other NAI precursors, − have been reported in the past decade. It is also noteworthy that a range of NAI cyclization reactions have been demonstrated on solid supports, especially for the synthesis of peptides and constrained peptidomimetics, but many of these reactions have been reviewed elsewhere. − …”