title: An approach toward homocalystegines and silyl-homocalystegines. acid-mediated migrations of acetates in seven-membered ring systems.
abstract: A short access to homocalystegine analogues silylated at C7 is described. The synthesis involves the desymmetrization of a (phenyldimethylsilyl)methylcycloheptatriene using osmium-mediated dihydroxylation, followed by the diol protection and a cycloaddition involving the remaining diene moiety and an acylnitroso reagent. Additions of the osmium and acylnitroso reagents were shown, through X-ray diffraction studies of the resulting major isomers, to occur anti and syn, respectively, relative to the SiCH(2) substituent. N-O bond cleavage on the resulting cycloadduct then produces the aminopolyol having a silylmethyl substituent. Oxidation of the C-Si bond also afforded an access to unusual amino-heptitols having five contiguous stereogenic centers. In the course of this work, we finally observed a unusual rearrangement taking place on cycloheptanone 18 substituted by two acetyl groups and a neighboring Boc-protected amine. A profound reorganization of the substituents on the seven-membered ring effectively took place under acidic conditions (TFA) leading to the thermodynamically more stable homocalystegine-type compound. DFT calculations of the conformational energy of isomeric silyl homocalystegines indicated that the product observed upon the acid-mediated rearrangement was the most stable of a series of analogues with various distributions of substituents along the seven-membered ring backbone. A tentative mechanism is proposed to rationalize the acetate migrations and inversions of the stereochemistry at various stereocenters.
authors.affiliation: Université de Bordeaux, Institut des Sciences Moléculaires, UMR-CNRS, Talence, France.
authors.forename: Redouane
authors.initials: R
authors.lastname: Beniazza
authors.forename: Valérie
authors.initials: V
authors.lastname: Desvergnes
authors.forename: Goverdhan
authors.initials: G
authors.lastname: Mehta
authors.forename: Nicolas
authors.initials: N
authors.lastname: Blanchard
authors.forename: Frédéric
authors.initials: F
authors.lastname: Robert
authors.forename: Yannick
authors.initials: Y
authors.lastname: Landais
mesh_terms: D000085:Acetates / Q000737:chemistry*; D003508:Cycloheptanes / Q000138:chemical synthesis* / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D017646:Organosilicon Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D014961:X-Ray Diffraction
chemical_list: D000085:Acetates; D003508:Cycloheptanes; D017646:Organosilicon Compounds; C000363:cycloheptanone