Synthesis of Polyketide Stereoarrays Enabled by a Traceless Oxonia‐Cope Rearrangement

Abstract

Polyketide antibiotics bearing skipped polyols represent a synthetic challenge. A SiCl4‐promoted oxonia‐Cope rearrangement of syn,syn‐2‐vinyl‐1,3‐diols was developed to forge an array of 1,5‐pentenediols, thus providing versatile motifs for the preparation of 1,2,3,5‐stereoarrays in a highly stereoselective manner. Further exploration with Sn(OTf)2 realized the rearrangement of a cross‐aldehyde which tactically warrants the utility of the current approach to access complex polyketides. The origin of high stereoselectivity is attributed to a chairlike anti‐conformation of the oxonium ion intermediate.

A Modular Synthesis of Antitumor Macrolide (–)‐Lasonolide A†

“…We envisioned that both enantiomers of racemic allenic alcohol can be evolved to form the individual fragments (Scheme 3). Following our previous exploration on the construction of tetrahydropyrans, [ 3c ] the quaternary carbon center in the A‐ring could be derived from the hydroboration‐allylation of R ‐ 11 , while the acetate form of S ‐antipode 12 is engaged into the preparation of the B‐ring ( vide infra ). However, the latter clearly requires an unprecedented sequential oxidation to install two hydroxy groups in a stereoselective manner.…”

“…In the continuing interest in the field of polyketide synthesis, our laboratory has embarked on the development of novel methods and efficient strategies to assemble complex bioactive polyketides. [ 3 ] During the hydroboration of allenic alcohol 1 (Scheme 1), we noticed a selection of different alkylboranes would provide various 1,3‐diols 2 in a highly diastereoselective manner after the allylation of the aldehydes, which were attributed to the stereodefined E ‐ or Z ‐allyboranes derived from the hydroboration of allenes. Moreover, a generally found boratropic rearrangement ([1,3]‐boratropic shift) [ 4 ] in allylboranes was largely suppressed due to the steric bulkiness of the alkyl substituents on boron.…”

“…The superior reactivity of disiamylborane (Sia 2 BH) to the alkene (the terminal olefin in allenes) and the slow 1,3‐shift of boron facilitate the kinetic hydroboration‐allylation to deliver an anti,anti ‐1,3‐diol motif with an all‐carbon quaternary center. [ 3c ] Moreover, the subsequent transformations, including a bidirectional oxa‐Michael cyclization, were able to produce diastereoisomers of tetrahydropyrans 3 in just 3—4 steps with excellent overall yields.…”

Stereodivergent Synthesis of Functionalized Tetrahydropyrans Accelerated by Mechanism‐Based Allylboration and Bioinspired Oxa‐Michael Cyclization

“…10:1) via an E-allylborane,w hich is derived from thermodynamic hydroboration of the allene (40 8 8Cf or 4h)( Scheme 1a). [7,8] Although bis(cyclohexyl)borane (Chx 2 BH) was effective in the work of Ariza and co-workers for the preparation of simpler anti,anti-1,3-diols in ak inetic fashion (0 8 8C, 3h), [9] thehydroboration of the 5 was slow,and at an elevated temperature formation of syn,syn-4a increased because of the increased presence of the E-allylborane arising from a1 ,3-boratropic shift. [10] Fortunately,u pon surveying other boranes and varying the reaction parameters (see the Table S2 in the Supporting Information), [8] disiamylborane (Sia 2 BH) was identified as as uperior kinetic borane reagent to afford anti,anti-4b,v ia afavorable transition state with Zallylborane (TS2 in Scheme 1b), in 90 %y ield and excellent diastereoselectivity (d.r.…”

Stereodivergent Synthesis of Functionalized Tetrahydropyrans Accelerated by Mechanism‐Based Allylboration and Bioinspired Oxa‐Michael Cyclization

“…[7,8] Although bis(cyclohexyl)borane (Chx 2 BH) was effective in the work of Ariza and co-workers for the preparation of simpler anti,anti-1,3-diols in ak inetic fashion (0 8 8C, 3h), [9] thehydroboration of the 5 was slow,and at an elevated temperature formation of syn,syn-4a increased because of the increased presence of the E-allylborane arising from a1 ,3-boratropic shift. It was known that 9-borabicyclo[3.3.1]nonane (9-BBN) would deliver syn,syn-4awith good diastereoselectivity (84 %y ield, d.r.…”