Tandem Conjugate Addition−Elimination for the Diastereoselective Synthesis of 4E-Alkenyl syn-1,3-Diols

Abstract

We have developed a tandem conjugate addition-elimination sequence for the diastereoselective synthesis of protected allylic syn-1,3-diols, starting from vinyl sulfones. The sulfonyl group was then reduced with sodium amalgam to furnish the E-olefin as the major isomer. This method was applied to the synthesis of a trisubstituted alkene modeling the C21-C25 fragment of Dolabelide C.

Syntheses of (−)-Cryptocaryolone and (−)-Cryptocaryolone Diacetate via a Diastereoselective Oxy-Michael Addition and Oxocarbenium Allylation

“…With this retrosynthetic plan in mind, our initial focus was to prepare acetate 14 , the precursor for the oxocarbenium allylation. As shown in Scheme , treatment of the previously reported TBDPS monoprotected homoallylic alcohol 9 (prepared by an asymmetric allylboration of 3-(( tert -butyldiphenylsilyl)oxy)propanal) with methyl acrylate ( 10 ) in the presence of Grubbs’ second-generation catalyst ( 11 ) under standard olefin cross-metathesis conditions provided the δ-hydroxy-( E )-α,β-unsaturated methyl ester 12 in 83% yield as a single diastereomer. ,, Following the Evans-acetal formation protocol, the δ-hydroxy enoate 12 was converted to the syn -benzylidene acetal 8 by addition of PhCHO and KO t Bu over 2 h in 67% yield as a single diastereomer, as determined by 1 H NMR analysis . Subsequent hydrogenolysis of 10 in the presence of H 2 and Pearlman’s catalyst [Pd(OH) 2 ] at rt in HOAc followed by cyclization/transesterfication led to the formation of the hydroxy lactone 13 in 71% yield.…”

Divergent Reactivity of Thioalkynes in Lewis Acid Catalyzed Annulations with Donor–Acceptor Cyclopropanes

“…Thio‐substituted five‐membered rings exhibit a bioactivity against diabetes, HIV, as wells as psychological, neurological, and proliferative disorders . Furthermore, the sulfur atom allows numerous unique chemical transformations, in addition to the hydrolysis to ketones, which is also possible with enamides and enolethers For example, vinyl sulfides are easily turned into electron‐deficient vinyl sulfones by oxidation,– which gives access to reductive desulfonylations,– and Michael additions –. Recently, we developed a new chemoselective alkynylation of thiols with cyclic hypervalent iodine reagents, making thioalkynes easily accessible starting materials, and therefore even more attractive partners for [3+2] annulations.…”

Synthesis of 1,3-Diols by O-Nucleophile Additions to Activated Alkenes

“…To circumvent this problem, Prunet and co-workers devised a cascade oxa-Michael/elimination sequence. 9 Condensation with the required aldehyde or ketone for the Julia olefination was performed on the vinyl sulfone, before the conjugate addition reaction, and the resulting alcohol was transformed into a good leaving group (OLG in Scheme 4). Treatment of these compounds with excess benzaldehyde and a full equivalent of base led to the benzylidene acetals flanked by a vinyl sulfone moiety.…”