Inés Pérez-Martín

Synthesis of oxa-aza spirobicycles by intramolecular hydrogen abstraction promoted by n-radicals in carbohydrate systems

The nitrogen-centred radical generated by reaction of an N-phosphoramidate or N-cyanamide, attached to a tri- or tetramethylene tether extended from the C-1 of a carbohydrate, with (diacetoxyiodo)benzene (DIB) and iodine can undergo a regio- and stereoselective intramolecular hydrogen atom transfer (HAT) reaction to furnish four different oxa-azaspirobicyclic systems: 1-oxa-6-azaspiro[4.4]nonane, 1-oxa-6-azaspiro[4.5]decane, 6-oxa-1-azaspiro[4.5]decane and 1-oxa-7-azaspiro[5.5]undecane. A tandem 1,5- or 1,6-HAT-oxidation-nucleophilic cyclisation mechanism is proposed.

Synthesis of oxa-aza spirobicycles by intramolecular hydrogen atom transfer promoted by N-radicals in carbohydrate systems

The nitrogen-centred radical generated by reaction of an N-phosphoramidate or N-cyanamide, attached to a tri- or tetramethylene tether extended from the C-1 of a carbohydrate, with (diacetoxyiodo)benzene (DIB) and iodine can undergo a regio- and stereoselective intramolecular hydrogen atom transfer (HAT) reaction to furnish four different oxa-azaspirobicyclic systems: 1-oxa-6-azaspiro[4.4]nonane, 1-oxa-6-azaspiro[4.5]decane, 6-oxa-1-azaspiro[4.5]decane and 1-oxa-7-azaspiro[5.5]undecane. A tandem 1,5- or 1,6-HAT-oxidation-nucleophilic cyclisation mechanism is proposed.

Easy Access to Modified Cyclodextrins by an Intramolecular Radical Approach

A simple method to modify the primary face of cyclodextrins (CDs) is described. The 6(I)-O-yl radical of α-, β-, and γ-CDs regioselectively abstracts the H5(II), located in the adjacent D-glucose unit, by an intramolecular 1,8-hydrogen-atom-transfer reaction through a geometrically restricted nine-membered transition state to give a stable 1,3,5-trioxocane ring. The reaction has been extended to the 1,4-diols of α- and β-CD to give the corresponding bis(trioxocane)s. The C2-symmetric bis(trioxocane) corresponding to the α-CD is a stable crystalline solid whose structure was confirmed by X-ray diffraction analysis. The calculated geometric parameters confirm that the primary face is severely distorted toward a narrower elliptical shape for this rim.

Intramolecular 1,8-Hydrogen Atom Transfer Reactions in Disaccharide Systems Containing Furanose Units

A previously developed 1,8-hydrogen atom transfer (HAT) reaction promoted by 6-O-yl alkoxyl radicals between the two pyranose units in Hexp-(1→4)-Hexp disaccharides has been extended to other systems containing at least a furanose ring in their structures. In Penf-(1→3)-Penf (A) and Hexp-(1→3)-Penf (B) disaccharides, the 1,8-HAT reaction and concomitant cyclization to a 1,3,5-trioxocane ring are in competition with radical β-scission of the C4-C5 bond and formation of dehomologated products. The influence of the stereoelectronic β-oxygen effect on the β-scission and consequently on the 1,8-HAT reaction has been studied using the four possible isomeric d-furanoses. d-xylo- and d-lyxo-derivatives afforded preferentially 1,8-HAT products, whereas d-arabino- and d-ribo-derivatives gave exclusively direct β-scission of the alkoxyl radical. When the 6-O-yl radical is on a pyranose ring, as occurs in Penf-(1→4)-Hexp (C), it has been shown to provide the cyclized products exclusively.

Sequential alkoxy radical fragmentation-intermolecular allylation in carbohydrate systems

The C-radical originated by β-fragmentation of carbohydrate anomeric alkoxy radicals, generated under reductive conditions by treatment of N-phthalimido glycosides with allyltri-n-butyltin/AIBN, may subsequently undergo an intermolecular allylation to give hept-1-enitol derivatives. These compounds can be useful chiral synthons for the synthesis of polyhydroxylated compounds.

Sequential Norrish Type II Photoelimination and Intramolecular Aldol Cyclization of α‐Diketones: Synthesis of Polyhydroxylated Cyclopentitols by Ring Contraction of Hexopyranose Carbohydrate Derivatives

The excitation of the innermost carbonyl of nono-2,3-diulose derivatives by irradiation with visible-light initiates a sequential Norrish type II photoelimination and aldol cyclization process that finally gives polyfunctionalized cyclopentitols. The rearrangement has been confirmed by the isolation of stable acyclic photoenol intermediates that can be independently cyclized by a thermal 5-(enolexo)-exo-trig uncatalyzed aldol reaction with high diastereoselectivity. In this last step, the large deuterium kinetic isotope effect found for the 1,5-hydrogen atom transfer seems to indicate that the aldol reaction runs through a concerted pericyclic mechanism. Owing to the ready availability of pyranose sugars of various configurations, this protocol has been used to study the influence of pyranose ring-substituents on the diastereoselectivity of the aldol cyclization reaction. In contrast with other pyranose ring contraction methodologies no transition-metal reagents are needed and the sequential rearrangement occurs simply by using visible light and moderate heating (0 to 60 °C).

Photochemistry of α‐Diketones in Carbohydrates: Anomalous Norrish Type II Photoelimination and Norrish–Yang Photocyclization Promoted by the Internal Carbonyl Group

A series of four α-diketones placed as 1α-pyruvoyl tethers on D-glucopyranose and D-glucopyranosiduronic acid skeletons was prepared in order to determine the influence of captodative and stereoelectronic effects on the regioselectivity of the hydrogen atom transfer (HAT) in Norrish type II photochemical processes. We observed that the 1,5-HAT regioselectivity can be switched between the two potentially abstractable syn-1,3-diaxial hydrogens at H6 and H8. Highly unusual photoproducts from Norrish type II photoelimination and Norrish-Yang photocyclization initiated by the excited internal carbonyl group were obtained, in some cases in excellent synthetic yield. The 1,5-HAT transition state in the Norrish type II photoelimination was investigated by photochemical experiments in the crystalline state.

Reductive Radical Cascades Triggered by Alkoxyl Radicals in the β-Cyclodextrin Framework

The generation and fate of 2I-VII,3I-VII,6II-VII-icosa- O-methyl-β-cyclomaltoheptaos-6I- O-yl radical under reductive conditions is described. Two radical cascade reactions are involved: the main one is triggered by a 1,8-HAT of the hydrogen at 5VIIC. The radical can reach the anomeric hydrogen at 1VC three sugar units ahead using a six-step sequence. The different hydrogen donor ability of the group 14 hydrides permits one to selectively stop the cascade at 5VIIC, 2VIC, and 4VIC to obtain β-CD with a β-l-Ido p unit, acyclic hepta-, and hexa-saccharide structures, respectively.