A Short Olefin Metathesis-Based Route to Enantiomerically Pure Arylated Dihydropyrans and α,β-Unsaturated δ-Valero Lactones

Abstract

The synthesis of arylated dihydropyrans and unsaturated lactones starting from enantiomerically pure alpha-hydroxy ketones (prepared by an enzyme-catalyzed benzoin condensation) is described. The key steps are a highly diastereoselective addition of vinyl metal compounds under chelate control and a ruthenium-catalyzed ring-closing olefin metathesis reaction. Elucidation of the relative configuration of the final products was achieved by NOE experiments.

One‐Flask Tethered Ring Closing Metathesis–Electrocyclic Ring Opening for the Highly Stereoselective Synthesis of Conjugated Z/E‐Dienes

“…For practical purposes, we aimed at the development of a one-flask sequence to avoid isolation and purification of the RCM product. The removal of highly colored Ru residues from olefin metathesis reactions by distillation or chromatography is often a serious problem, [44] and we knew from previous work [45][46][47] that this is particularly true for the metathesis-based synthesis of unsaturated lactones due to their high polarity. Furthermore, for operational simplicity, a one-flask sequence should ideally proceed without exchange or removal of solvents, simply by addition of the appropriate catalysts and reagents at the appropriate time.…”

Palladium‐Catalyzed O‐Allylation of α‐Hydroxy Carbonyl Compounds

“…Spectroscopic data are identical to those reported in the literature. [7] rac-Acetic acid 2-allyloxy-3-oxo-3-phenyl-propyl ester (11g): Obtained from 10g [49] (104 mg, 0.5 mmol) as a colorless liquid; yield: 65 mg (52%).…”

“…[4] The same phenomenon was observed for a-hydroxy ketones such as benzoin. [7] Racemization and undesired Wittig rearrangements can be avoided by using trichloroacetimidates as allylating agent [21] or allyl bromide in the presence of excess silver oxide. [22,23] We have successfully used the latter method for a-hydroxy esters.…”

“…For 3-hydroxypropiophenone (6) and substituted derivatives this side reaction becomes a serious limitation, as approximately 50% of the starting material are converted via this pathway (Scheme 2). [7] This observation, together with the economical (overstoichiometric amounts of expensive Ag 2 O are required) and ecological (generation of heavy metal-containing waste in large quantities) drawbacks of this method led us to evaluate the potential of a Pd-catalyzed allylation process for this transformation. The Pd-catalyzed allylation has been widely applied to C-nucleophiles and is one of the most important C À C bond-forming reactions.…”

Preparation of γ-trimethylsilylallyldibutylstannane grafted on solid support: a clean and easily recyclable reagent for the synthesis of 2,6-disubstituted dihydropyrans

“…1 In addition, the olefin function of these compounds is particularly attractive since it could serve as useful building blocks for further functionalization in order to obtain polysubstituted tetrahydropyrans. 2,3 As a result, several approaches have been reported for the construction of cis-2,6-disubstituted dihydropyrans such as the hetero Diels-Alder cycloadditions, 4-7 the intramolecular silylmodified Sakurai reaction (ISMS), 8 the olefin metathesis, [9][10][11] and the Prins-cyclization. 12 The Prins-cyclization, which involves the coupling of homoallylic alcohols with simple carbonyl compounds under acid catalysis is one of the most effective reaction for the preparation of either tetrahydropyran or dihydropyran rings.…”