Radical cyclisations of methylenecyclopropane derivatives

This thesis is concerned with the synthesis of compounds containing a methylenecyclopropane moiety and their intramolecular radical cyclisations, in an effort to develop new approaches to ring systems. The first chapter describes the synthesis of monosubstituted methylenecyclopropane radical precursors (82) and (95), and their radical cyclisation with tributyltin hydride and catalytic AIBN to give the unexpected cyclohexene (83) and methylenecyclohexane (84). A mechanism for the formation of compounds (83) and (84) is proposed. vskip 1.5cm Chapter two describes the synthesis and radical cyclisation of disubstituted methylenecyclopropylalkyl derivatives (108) to (110) and (118) to (120). vskip 1.5cm We found that methylenecyclopropylpropyl radicals cyclise in a 5-exo fashion, followed by a ring expansion to produce six-membered rings. In the case of methylenecyclopropylbutyl radicals, depending on the substitution of the cyclopropane ring, exo or endo cyclisation is favoured. If there is initial exo cyclisation, there is exo or endo opening of the intermediate cyclopropylmethyl radical depending on the substitution of the cyclopropane ring. No cyclised products were obtained with methylenecyclopropyl pentyl radicals under these conditions. Chapter three describes the use of malonyl radicals with various chain lengths and substitution. Using the atom transfer methodology, methylenecyclopropylpropyl radicals cyclise almost exclusively in a 5-exo fashion, followed by endo opening of the intermediate cyclopropylmethyl radical to produce six-membered rings. Methylenecyclopropylbutyl and pentyl radicals cyclise preferentially in an endo fashion. Finally, chapter four describes our preliminary approach to bicyclic systems by tandem cyclisation of methylenecyclopropylpropyl radical (207). vskip 1.7cm</p

Cleavage of N−O Bonds Promoted by Samarium Diiodide: Reduction of Free or N-Acylated O-Alkylhydroxylamines

2 páginas, 1 tabla.Financial support provided by DGICYT (grant nos. SAF94-0818-C02-02 and PB93- 0127-C02-01), CICYT (grant no. CE93-0023), Comunidad Autónoma de Madrid-Consejería de Educación y Cultura (grant no. AE-0094/94), and EU (Human Capital and Mobility Program; Contract ERBCHRXCT 92- 0027) is also gratefully acknowledged.Peer reviewe

A New Synthetic Approach to the Carbocyclic Core of Cyclopentane-Type Glycosidase Inhibitors: Asymmetric Synthesis of Aminocyclopentitols via Free Radical Cycloisomerization of Enantiomerically Pure Alkyne- Tethered Oxime Ethers Derived from Carbohydrates

9 páginas, 7 esquemas.-- Supporting Information Available: Experimental procedures and 1H and 13C NMR spectra for compounds 21b, 21c, 22,25a 26-29, 35-44 (13 pages).The synthesis of compounds 6-8, derived from 2,3:5,6-bis-O-isopropylidene-d-mannofuranose (3), and the preparation of products 16 and 17, obtained from 2,3-O-isopropylidene-d-ribose (13) is reported. The first free radical cyclization of enantiomerically pure alkyne-tethered oxime ethers derived from carbohydrates (6, 8, 16, and 17) is described. These radical precursors have been submitted to cyclization with tributyl or triphenyltin hydride plus triethylborane to yield, after ring closure, the aminocyclopentitols 9−12 and 18−20, respectively. These carbocycles have been obtained as mixtures of Z and E vinyltin isomers, but with excellent diastereoselection at the new stereocenter formed during the ring closure. After protodestannylation, only one diastereoisomer was detected and isolated. The absolute configuration at the new stereocenter formed during the carbocyclization has been established by detailed 1H NMR analysis. The specific transformation of compound 19 (or 20) into aminocyclitol 24 is described. Compound 24 is an analogue of the aminocyclopentitol moiety of trehazolin (1a), a known and powerful glycosidase inhibitor of trehalase. From these results, we can conclude that a new method for the asymmetric synthesis of aminocyclitols of biological interest is now available.The authors thank DGICYT (SAF94-0818-C02-02), CICYT (CE93- 0023), Comunidad Autónoma de Madrid-Consejería de Educación y Cultura-(AE-0094/94), and EU (Human Capital and Mobility; Contract no. ERBCHRXCT 92- 0027) for generous financial support.Peer reviewe

Palladium-catalyzed reduction of a propargylic acetate derived from a sugar with SmI2. Some unexpected

4 páginas, 3 esquemas.We describe here the unexpected result that we have observed in the palladium-catalyzed reduction of the propargylic acetate 3 derived from a sugar with samarium diiodide. In addition to traces of the expected allene derived product 4, we have obtained mostly α-elimination leading to enynes 5 in moderate yield.The authors thank the DGICYT (SAF 94-0818-C02) and Comunidad Autónoma de Madrid-Consejería de Educación y Cultura- (AE-0094/94) and EU (Human Capital and Mobility; Contract no. ERBCHRXCT 92-0027) for generous financial support.Peer reviewe

Intramolecular reductive coupling of carbonyl-tethered oxime ethers promoted by samarium diiodide: A powerful method for the stereoselective synthesis of aminocyclopentitols

2 páginas, 3 esquemas.-- A part of this work was presented at the XVIIth International Carbohydrate Symposium, Ottawa, July 1994.-- Supporting Information Available: Experimental procedures and characterization data for all new compounds and tables of lH NMR and 2D NOESY cross-peak intensities for cyclopentane products (8 pages).Financial support by DGICYT (Grant Nos. PB93-0127-C02-01 and SAF94-0818-CO2- 02), CICYT (Grant No. CE93-0023), Comunidad Autónoma de Madrid (Grant No. AE-0094/94), and the European Union (Human Capital and Mobility Programme; contract ERBCHRXCT 92-0027) is gratefully acknowledged.Peer reviewe

Free radical cycloisomerization of enantiomerically pure alkyne-tethered oxime ethers: A new method for the asymmetric synthesis of aminocyclopentitols

4 páginas, 4 esquemas.We describe for the first time the free radical cyclization of enantiomerically pure alkyne-tethered oxime ethers obtained from carbohydrates. The synthesis of compounds 6 and 7, obtained from 2,3-O-isopropylidene-D-ribose 3 is reported. These radical precursors have been submitted to cyclization with tributyl or triphenyltin hydride plus triethylborane, to yield, after ring closure, the aminocyclopentitols 8–10. These carbocycles have been obtained as mixtures of Z and E vinyltin isomers, but with excellent diastereoselection. After protodestannylation only one diastereoisomer was detected. The absolute configuration at the new stereocenter formed during the ring closure has been established by detailed 1H NMR analysis. The specific transformation of compound 9 (or 10) into aminocyclitol 14 is described. From these results, we can conclude that a new method for the asymmetric synthesis of aminocyclopentitols of biological interest is now available.The authors thank the DGICYT (SAF 94-0818-C02-02), CICYT (CE93-0023), Comunidad Autónoma de Madrid-Consejería de Educación y Cultura-(AE-0094/94) and EU (Human Capital and Mobility Programme; Contract no. ERBCHRXCT 92-0027) for generous financial support.Peer reviewe

Synthesis of Aminocyclitols by Intramolecular Reductive Coupling of Carbohydrate Derived δ- and ε-Functionalized Oxime Ethers Promoted by Tributyltin Hydride or Samarium Diiodide

16 páginas, 2 figuras, 18 esquemas, 1 tabla.-- Supporting Information Available: Experimental procedures and characterization data for compounds 7b-e, 23, 54, and 56, and tables of 1H NMR and 2D NOESY cross-peak intensities for the carbocyclic products 39, 43, 44a-c, 45, 50ad, 51a,b, 52a,b, 65a-c (8 pages).The intramolecular reductive coupling of a series of simple or polyoxygenated oxime ethers δ- or ε-functionalized with bromide, α,β-unsaturated ester, aldehyde, or ketone groups is reported. The cyclization of a nitrile-tethered aldehyde is also studied. These reductive couplings are promoted by tributyltin hydride or samarium diiodide. The reactions proceed under mild conditions, in good chemical yield, and with high stereoselectivity. When applied to highly functionalized substrates derived from carbohydrates, this approach provides a selective entry to enantiomerically pure aminocyclitols of varying regio- and stereochemistry. In particular, the reductive coupling reaction of carbonyl-tethered oxime ethers promoted by samarium diiodide can be performed in a one-pot sequence, following a Swern oxidation step, allowing the direct transformation of hydroxyl-tethered oxime ethers into the corresponding aminocyclitols. Moreover, the resultant O-benzylhydroxylamine products of these cyclizations can be further reduced in situ with excess samarium diiodide, in the presence of water, to the corresponding amino alcohols in excellent yields. Some transformations of these compounds are discussed.Financial support from DGICYT (grants PB93-0127-C02-01, SAF97-0048-C02-02 and SAF94-0818-C02-02), CICYT (grant CE93-0023), Comunidad Autónoma de Madrid (grant AE-0094/94), and the European Union (Human Capital and Mobility Programme; contract ERBCHRXCT 92-0027) is greatefully acknowledged.Peer reviewe