Asymmetric syntheses of diarylheptanoid natural products (−)-centrolobine and (−)-de-O-methylcentrolobine via hetero-Diels–Alder reaction catalyzed by dirhodium(II) tetrakis[(R)-3-(benzene-fused-phthalimido)-2-piperidinonate]

Abstract

Abstract-Catalytic asymmetric syntheses of (-)-centrolobine and (-)-de-O-methylcentrolobine have been achieved, incorporating a hetero-Diels-Alder (HDA) reaction between 4-aryl-2-silyloxy-1,3-butadienes and phenylpropargyl aldehyde derivatives as a key step. The HDA reaction using dirhodium(II) tetrakis[(R)-3-(benzene-fused-phthalimido)-2-piperidinonate], Rh 2 (R-BPTPI) 4 , as a chiral Lewis acid catalyst provides exclusively cis-2,6-disubstituted tetrahydropyran-4-ones in up to 93% ee.

The Biomimetic Synthesis and Final Structure Determination of (+)‐ and (−)‐Centrolobine, Naturally Occurring Diarylheptanoid 2,6‐cis‐Disubstituted Tetrahydro‐2H‐pyrans

“…It was achieved by reductive cyclization of an optically active hydroxysulfinyl ketone and for the first time ever confirmed the (2S,6R)-configuration of (À)-1 as earlier proposed by us [4]. In the course of further synthetic activities, the stereoselective construction of the tetrahydro-2H-pyran ring has been achieved by Prins-type cyclization [18] and secondary modifications thereof [19], by reductive etherification of d-(trialkylsilyloxy)-substituted ketones [20], by crossmetathesis procedures [21] and related strategies [22] [23], by a diastereoselective ring rearrangement metathesis -isomerization sequence [15], by Maitland -Japp reaction [24], by intramolecular oxy-Michael reaction [25], by Lewis-acid mediated reactions such as cyclization of a 1,5-diol [26] or opening of an epoxide precursor [23], by heteroDiels -Alder reaction between 4-aryl-2-(silyloxy)buta-1,3-dienes and phenylpropargylaldehyde (¼ 3-phenylprop-2-ynal) derivatives [27] or related enantioselective multistep procedures [28] 6 ), by intramolecular Barbier-type cyclization of iodoesters with an organolithium base [29], and by stereoselective synthesis of cyclic ethers via Pdcatalyzed intramolecular addition of alcohols to phosphonoallyl carbonates [30].…”

Ionic liquid assisted synthesis of six-membered oxygen heterocycles

“…Only cis-disubstituted tetrahydropyran was observed. The catalytic hydrogenation removed the benzyl group in 98% yield [179][180][181][182][183][184][185][186][187][188][189][190][191][192][193][194][195][196][197].…”

Chemoselective Reduction and Alkylation of Carbonyl Functions Using Phosphonium Salts as an <i>in Situ</i> Protecting Groups

“…[36][37][38] Asymmetric syntheses of centrolobine have been reported by several groups, but they involve multiple steps and/or give low yields. [39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] Our synthetic route is summarized in Chart 7. This enantioselective synthesis was accomplished in five steps from commercially available cyclopentene 3; the overall yield was 75%, which is the highest total yield reported for the asymmetric synthesis of (+)-centrolobine.…”