Heterocycles via intramolecular platinum-catalyzed propargylic substitution

Abstract

We report a Pt(II)-catalyzed cyclization of nucleophile-tethered propargylic acetates yielding substituted heterocycles containing multiple heteroatoms including morpholines, dioxanes and sulfamates with high cis-selectivity.

Studies of Highly-Ordered Heterodiantennary Mannose/Glucose-Functionalized Polymers and Concanavalin A Protein Interactions Using Isothermal Titration Calorimetry

“…39 Furthermore, this polymerizable scaffold 4 increases the structural rigidity of the neoglycopolymers and allows efficient access to the corresponding copolymers between α-mannose and β-glucose units. 39 Accordingly, the Mitsunobu coupling of 4 with alcohol linker 5 40 provided 6 in 98% yield (Scheme 1). Removal of the tert -butyl silyl (TBS) ether group afforded 82% yield of primary alcohol 7 , which served as a glycosyl acceptor in the glycosylation with trichloroacetimidate donor 8 mediated by 20 mol% of trimethylsilyl triflate (TMSOTf).…”

Scope and advances in the catalytic propargylic substitution reaction

“…Brabander and co-workers in 2011 demonstrated that uhydroxy propargylic acetates 342 with a side chain containing Boc-protected nitrogen atom underwent intramolecular substitution in presence of 2.5 mol% Zeise's dimer in THF medium to form 2,6-disubstituted morpholines 343 with the predominance of the cis-isomer in good yields at room temperature, Scheme 169. 209 The methodology has been extended to synthesize cis-2,6disubstituted-1,4-dioxanes 344 from oxygen tethered u-hydroxy propargylic acetates under similar reaction conditions in good yield and high diastereoselectivity. Other classes of molecules synthesized using this methodology included 3-substituted morpholines 345 and cyclic sulfamates 346 from various heteroatom tethered propargylic acetates, Fig.…”

“…One classic example reported in 2008 was Zeise's dimer [(CH 2 CH 2 )Cl 2 Pt] 2 catalyzed intramolecular cyclization of ω-substituted propargylic acetates to furnish heterocycles. 209 Despite the therapeutic importance of the cis -2,6-disubstituted morpholines there are only a few synthetic methodologies available for them.…”

“…Brabander and co-workers in 2011 demonstrated that ω-hydroxy propargylic acetates 342 with a side chain containing Boc-protected nitrogen atom underwent intramolecular substitution in presence of 2.5 mol% Zeise's dimer in THF medium to form 2,6-disubstituted morpholines 343 with the predominance of the cis -isomer in good yields at room temperature, Scheme 169 . 209 …”

Transition‐Metal‐Catalyzed Propargylic Substitution of Propargylic Alcohol Derivatives Bearing an Internal Alkyne Group

“…De Brabander's group also revealed that the platinum catalyst system can be leveraged to the synthesis of internal alkyne‐substituted heterocyclic compounds (Scheme 49). [66] This method allowed the access to a number of morpholine, 1,4‐dioxane, and cyclic sulfamate derivatives bearing the propargyl substituent.…”