Masataka Oishi

Methylaluminum bis(4-substituted-2,6-di-tert-butylphenoxide) as an efficient nonchelating Lewis acid: Application to asymmetric Diels-Alder reaction and diastereoselective alkylation to alkoxy carbonyl substrates

Abstract The exceptionally bulky methylaluminum bis(4-substituted-2,6-di- tert -butylphenoxide) such as MAD or MABR can be successfully utilized as a highly efficient nonchelating Lewis acid for achieving high stereoselectivity in 1,n asymmetric induction in cyclic as well as acyclic systems. Thus, Diels-Alder reaction of the acrylate of D-pantolactone and cyclopentadiene in the presence of such bulky organoaluminum reagents exhibits high diastereoselectivity not observable with ordinary Lewis acids. Furthermore, high levels of nonchelation controlled diastereoselectivity are present in Grignard- and organolithium-types of addition to α- and β-alkoxy cyclic ketones in the presence of MAD or MABR.

Highly efficient synthesis of 2,2′-anhydro-1-(3′-bromo-3′-deoxy-5′-O-trityl-β-D-arabinofuranosyl)thymine and its derivatives from an unsaturated thymine nucleoside

Reaction of 5′-O-trityl-2′,3′-thymidinene 1 with hypobromous acid gave (5R,6R)-2,2′-anhydro-5-bromo-1-(3′-bromo-3′-deoxy-5′-O-trityl-β-D-arabinofuranosyl)-6-hydroxy-5, 6-dihydrothymine 3a and its (5S,6S)-trans isomer 4a. Similarly, 6-methoxy analogues (3b and 4b) and 6-acetoxy analogues (3c and 4c) of 3a and 4a were synthesized. Compounds 3a and 4a were converted into the corresponding 5,6-epoxy derivatives, 5 and 6. Deoxygenation of oxiranes 5 and 6 with Ph3P gave 2,2′-anhydro-1-(3′-bromo-3′-deoxy-5′-O-trityl-β-D-arabinofuranosyl)thymine 7, which was also obtainable in excellent yields from compounds 3a, b or/and 4a, b by treatment with Ph3PNaHCO3, or directly from unsaturated furanose 1 by one-pot synthesis via methyl ethers 3b and 4b or acetates 3c and 4c. Compound 7 was deprotected to give the mother compound 8 and was also converted into the 2, 3-lyxo epoxy thymine furanosides, 11 and 12, in high yields.