Oxabicyclo[3.2.1]octenes in Organic SynthesisDirect Ring Opening of Oxabicyclo[3.2.1] Systems Employing Silyl Ketene Acetals in Concentrated Solutions of Lithium Perchlorate−Diethyl Ether:  Application to the Synthesis of the C(19)−C(27) Fragment of Rifamycin S

Abstract

[figure: see text] The direct opening at the bridgehead of oxabicyclo[3.2.1]octenes employing silyl ketene acetals in 4.0-5.0 M lithium perchlorate in diethyl ether has been realized, which gives rise to highly functionalized cycloheptadienes that can be further manipulated for use in natural product synthesis. The bridgehead opening reaction has been employed in the construction of the C(19)-C(27) fragment of Rifamycin S.

Taking Up the Cudgels for Perchlorates: Uses and Applications in Organic Reactions under Mild Conditions

“…Since two exhaustive reviews have recently appeared in the literature, [13] here we report only a few more recent applications. Grieco [14] reported the direct opening of oxabicyclo[3.2.1]octenes 1 (Scheme 1) at the bridgehead on treatment with silyl ketene acetals in LPDE (4.0 ), giving the highly functionalized cycloheptadienes 2, which can be fur- Scheme 1. ther manipulated for use in natural product syntheses. The bridgehead opening reaction has been employed in the construction of the C(19)-C(27) fragment of Rifamycin S. [14] Saidi [15] described a highly diastereoselective one-pot, three-component method for the preparation of several secondary amines and amino esters.…”

“…Grieco [14] reported the direct opening of oxabicyclo[3.2.1]octenes 1 (Scheme 1) at the bridgehead on treatment with silyl ketene acetals in LPDE (4.0 ), giving the highly functionalized cycloheptadienes 2, which can be fur- Scheme 1. ther manipulated for use in natural product syntheses. The bridgehead opening reaction has been employed in the construction of the C(19)-C(27) fragment of Rifamycin S. [14] Saidi [15] described a highly diastereoselective one-pot, three-component method for the preparation of several secondary amines and amino esters. Treatment of aliphatic or aromatic aldehydes with chiral amines and functionalized organozinc reagents in the presence of trimethylsilyl chloride (TMSCl) in LPDE (5 ) produces N-alkylamino esters or N,N-dialkylamines 3 in good yields and with high diastereoselectivities (Scheme 2).…”

Oxabicyclo[3.2.1]octenes in Organic Synthesis: Direct Ring Opening of Oxabicyclo[3.2.1] Ring Systems with Diisobutylaluminum Hydride and a Silyl Ketene AcetalSynthesis of the Chiral C(19)−C(26) and C(27)−C(32) Fragments of Scytophycin C

“…With the hydride opened product 4 in hand, the stage was set for determining and increasing the enantiomeric excess. Although conversion of 4 into the corresponding Mosher ester 10 clearly revealed by 1 H NMR analysis that the enantiopurity of 4 was 75% ee, the resulting diastereomeric esters were not readily separable. After surveying a series of mandelic acid derivatives, it was found that coupling (DCC, cat.…”

“…We recently disclosed a procedure 1 for the direct bridgehead opening of activated oxabicyclic molecules employing silyl ketene acetals in the highly polar medium 4.0 M lithium perchlorate-diethyl ether (LPDE) 2 [eq 1]. We now wish to disclose (1) the desymmetrization of the starting oxabicyclo-[3.2.1]octenone 1 via enantioselective deprotonation [eq 2],…”

“…We recently disclosed a procedure for the direct bridgehead opening of activated oxabicyclic molecules employing silyl ketene acetals in the highly polar medium 4.0 M lithium perchlorate−diethyl ether (LPDE)[eq 1]. We now wish to disclose (1) the desymmetrization of the starting oxabicyclo[3.2.1]octenone 1 via enantioselective deprotonation [eq 2], (2) the direct bridgehead opening of the oxa bridge of 2 employing diisobutylaluminum hydride 3 leading to the direct formation of cycloheptenone 4 [eq 3], (3) the use of 4 in the construction of the C(27)−C(32) fragment 7 of Scytophycin C ( 5 ), and (4) the transformation of optically active 3 into the C(19)−C(26) subunit 6 of 5 .…”