1037069-29-6Relevant articles and documents
Spiro- and Bicycloannulation of Sulfoximine-Substituted 2-Hydroxy-dihydropyrans: Enantioselective Synthesis of Spiroketals, Spiroethers, and Oxabicycles and Structure of Dihydropyran Oxocarbenium Ions
Lejkowski, Michal,Banerjee, Prabal,Raabe, Gerhard,Runsink, Jan,Gais, Hans-Joachim
, p. 529 - 553 (2014)
A modular enantioselective synthesis of spiroketals, spiroethers, and oxabicycles, each containing a dihydropyran subunit, is described. It is based on the 2,2-spiro- and 2,6-bicycloannulation of sulfoximine-substituted 2-hydroxy-dihydropyrans. Key steps of the spiroannulations are the ring-closing metathesis of the corresponding 2,2-oxadienyl and 2,6-dienyl dihydropyrans and Prins cyclization of 2-alkenyl 2-hydroxy-dihydropyrans. Ring-closing metathesis of the corresponding 2,6-dienyl dihydropyrans gave oxabicycles with oxabicyclo[4.3.1]decane skeletons. These routes were extended to the synthesis of spiroketals and spiroethers incorporating additional annulated six-membered rings. Diastereoselective Prins cyclization of mono- and bicyclic 2-alkenyl-2-hydroxy-dihydropyrans was highly selective and afforded chloro-substituted spirocycles. Substituted 2-hydroxy-dihydropyrans were obtained through cyclization of δ-hydroxy ketones, which were synthesized from enantiomerically pure sulfoximine-substituted homoallylic alcohols through lithiation and trapping of the α-lithioalkenylsulfoximines with unsaturated aldehydes, followed by allylic oxidation. Inter- and intramolecular glycosidations of the 2-hydroxy-dihydropyrans with O- and C-nucleophiles proceeded with high stereoselectivities and furnished 2,6-trans-configured glycosides. Dihydropyran oxocarbenium ions are most likely intermediates in the glycosidations. According to ab initio calculations, sulfoximine- and trimethyl-substituted dihydropyran oxocarbenium ions adopt a half-chair-like conformation. The energy difference between the oxocarbenium ion with pseudoaxial and the one with pseudoequatorial methyl groups is very small. A transition state model for their reactions with nucleophiles is proposed. It features a half-chair-like conformation, a pseudoequatorial C6 substituent, and an anti-addition of the nucleophile along an axial trajectory to C2 that produces an anti-periplanar lone pair at the O atom. A similar transition state model allows a general explanation for the trans stereoselectivity of the reactions between C6-substituted dihydropyran oxocarbenium ions and nucleophiles.
Spiro- and bicycloannulation of sulfoximine-substituted 2-hydroxy-dihydropyrans: Enantioselective synthesis of spiroketals, spiroethers, and oxabicycles and structure of dihydropyran oxocarbenium ions
Lejkowski, Michal,Banerjee, Prabal,Raabe, Gerhard,Runsink, Jan,Gais, Hans-Joachim
, p. 529 - 553 (2014/02/14)
A modular enantioselective synthesis of spiroketals, spiroethers, and oxabicycles, each containing a dihydropyran subunit, is described. It is based on the 2,2-spiro- and 2,6-bicycloannulation of sulfoximine-substituted 2-hydroxy-dihydropyrans. Key steps of the spiroannulations are the ring-closing metathesis of the corresponding 2,2-oxadienyl and 2,6-dienyl dihydropyrans and Prins cyclization of 2-alkenyl 2-hydroxy-dihydropyrans. Ring-closing metathesis of the corresponding 2,6-dienyl dihydropyrans gave oxabicycles with oxabicyclo[4.3.1]decane skeletons. These routes were extended to the synthesis of spiroketals and spiroethers incorporating additional annulated six-membered rings. Diastereoselective Prins cyclization of mono- and bicyclic 2-alkenyl-2-hydroxy-dihydropyrans was highly selective and afforded chloro-substituted spirocycles. Substituted 2-hydroxy-dihydropyrans were obtained through cyclization of δ-hydroxy ketones, which were synthesized from enantiomerically pure sulfoximine-substituted homoallylic alcohols through lithiation and trapping of the α-lithioalkenylsulfoximines with unsaturated aldehydes, followed by allylic oxidation. Inter- and intramolecular glycosidations of the 2-hydroxy-dihydropyrans with O- and C-nucleophiles proceeded with high stereoselectivities and furnished 2,6-trans-configured glycosides. Dihydropyran oxocarbenium ions are most likely intermediates in the glycosidations. According to ab initio calculations, sulfoximine- and trimethyl-substituted dihydropyran oxocarbenium ions adopt a half-chair-like conformation. The energy difference between the oxocarbenium ion with pseudoaxial and the one with pseudoequatorial methyl groups is very small. A transition state model for their reactions with nucleophiles is proposed. It features a half-chair-like conformation, a pseudoequatorial C6 substituent, and an anti-addition of the nucleophile along an axial trajectory to C2 that produces an anti-periplanar lone pair at the O atom. A similar transition state model allows a general explanation for the trans stereoselectivity of the reactions between C6-substituted dihydropyran oxocarbenium ions and nucleophiles. Spiroannulation of 2-hydroxy-dihydropyrans through RCDEM of the corresponding 2,2-dienyl dihydropyrans and Prins cyclization of 2-alkenyl dihydropyrans gave sulfoximine-substituted unsaturated spiroketals and spiroethers. RCDEM of 2,6-dienyl dihydropyrans afforded oxabicycles. A transition state model for the 2,6-trans-stereoselective glycosidation of dihydropyran oxocarbenium ions is proposed. Copyright
