The Influence of the 2-Alkoxy Group and of C-5 Substituents on the Direction of Reductive Cleavage of 2-Alkoxytetrahydrofurans by AlH₂Cl in Ether Solution

Abstract

The AIH,C1 hydrogenolysis of ether solutions of 2-alkoxytetrahydrofurans in which the alkoxy group is either CH,O, C,H50, i-C,H,O, or t-C4Hg0, gives only those products resulting from ring C 4 bond cleavage. However, substituents at C-5 of 2-methoxytetrahydrofuran exert a strong effect on the ratio of ring to exo C 4 bond cleavage. Thus, alkyl (electron donor) groups at C-5 promote an increase in the amount of exo cleavage, the proportion increasing from 62.5 to 100% as the C-5 alkyl group is changed from CH, to I-C,Hg. In contrast, electron withdrawing substituents, CH,OCH,-and C,H,, at C-5 favor ring cleavage to the extent of 93 and 84% respectively.The results are interpreted in terms of the influence that these substituents exert through their electronic properties on the relative ease of attainment of the transition state leading to either ring C 4 or exo C-0 bond cleavage. However, evidence is provided to show that the bulk steric effect of these substituents also controls, though to a minor extent, the proportion of ring to exo cleavage.Les hydrogenolyses par AIH,CI de solutions etherees de tdtrahydrofurannes alcoolates-2, oh le group alcoolate est soit CH,O, C,H,O, I-C,H,O, ou t-C4H,0, conduisent uniquement aux produits resultant de la rupture de la liaison C-0 du cycle. Cependant, les substituants sur C-5 dans le methoxy-2 tetrahydrofuranne, exercent un effet important sur le rapport: rupture de la liaison C 4 du cycle sur rupture de la liaison C-0 exocyclique. C'est ainsi que des groupes alkyles (donneurs d'tlectrons) sur C-5 favorisent le pourcentage de clivage exocyclique; les pourcentages augmentant de 62.5 a 100% si le groupe alkyle passe de CH, a t-C4Hg. Au contraire, des substituants en C-5 attracteurs d'electrons, CH,OCH,-et C,H5, favorisent la rupture du cycle jusqu'a des proportions de 93 et 84% respectivement.Les resultats sont interpretes en fonction de I'influence qu'exercent ces substituants, par leurs proprietes electroniques, sur la facilite relative de formation de I'btat de transition conduisant ulterieurement a la rupture de la liaison C 4 soit du cycle soit exocyclique. Cependant, des preuves ont ete apportks afin de montrer que I'encombrement sterique de ces substituants contrBle egalement, bien qu'a un degre moindre, les proportions de clivage cyclique et exocyclique.

A Comparison of Monocyclic and Bicyclic Phospholanes as Acyl-Transfer Catalysts

“…Furthermore, an attempt to improve enantioselectivity by introducing additional steric constraints quickly encountered reactivity limitations. Thus, 2- tert -butylphospholane 15a , available via a similar sequence from diol 13 , gave a small increase in enantioselectivity (Table , entry 4; s = 5.6). However, reactivity dropped considerably compared to that of 11a .…”

Reduction of Acetals, Azaacetals and Thioacetals to Ethers

“…With HAICl2 70 and H2AICI,71,72 comparable furanosides react more rapidly than pyranosides and tend to give more ring cleavage (Tables 4 and 5), consistent with the greater basicity of THF.73 Increased branching in the alkoxy group OR also promotes ring cleavage, but substituents on the other side of the acetal system (R I) promote side chain cleavage. 72 The LAH-BF3 reagent resembles the less-halogenated alanes (Table 5). These effects have been ascribed 7 1,72 to the electron-releasing effect of branched alkyl groups, which, located at the oxygen end of the oxocarbonium ion, would tend to stabilize it, thereby promoting cleavage at the other oxygen atom.…”