Catalyzed Asymmetric DielsAlder Reactions of Benzoquinone. Total Synthesis of (−)‐Ibogamine

Abstract

Dedicated to Professor Dieter Seebach on the occasion of his 65th birthday and in recognition of his numerous contributions to asymmetric synthesis.The DielsÀAlder reaction of 1,4-benzoquinone with 1,3-dienes catalyzed by Mikami×s [Ti{(S)-binol(2 À)}Cl 2 ] complex (binol [1,1'-binaphthalene]-2,2'-diol) gives cycloadducts in good yield and in high enantiomer excess. A model is proposed to explain the observed absolute configuration of cycloadducts, and the reaction is used as the key step in an asymmetric synthesis leading to the alkaloid (À)-ibogamine.1. Introduction. ± The asymmetric DielsÀAlder reaction has become one of the most widely used constructs for the assembly of enantiomerically enriched chiral carbocycles [1]. In its catalyzed version, the reaction offers an especially powerful synthetic method, which can lead to adducts from achiral materials in good yield and high enantiomer excess (ee) at or below room temperature [2]. Most catalyzed cycloadditions have relied on two-point ligation of an achiral dienophile with the chiral catalyst to form a relatively rigid, highly asymmetric, activated complex [3]. Typical dienophiles in this class are b-dicarbonyl compounds, where chelation with a metal such as titanium bound to a chiral ligand creates a complex in which only one face of the dienophile is exposed for reaction with its diene partner. As a result, asymmetric DielsÀAlder additions in this mode can be very efficient. The asymmetric DielsÀAlder reaction with a dienophile such as a simple a,b-unsaturated ketone or a 1,4-quinone raises the question of whether stereocontrol can be exercised effectively by single-point ligation of a chiral catalyst with the lone pair of electrons of only one carbonyl group. This question was first answered in the affirmative by Mikami and co-workers who showed that the reaction of 1,4-naphthoquinone with 1-methoxybuta-1,3-diene in the presence of a [Ti IV {binol(2 À)}] catalyst (binol [1,1'-naphthalene]-2,2'-diol) led to diketone 1 in high ee (Scheme 1) [4]. Subsequently, we found that benzoquinone in the presence of the Mikami catalyst underwent DielsÀAlder cycloaddition with a 1,3-diene derivative in similarly high ee [5]. Other examples from the laboratories of Corey [6] and Nicolaou [7] illustrate the participation of substituted benzoquinones in asymmetric DielsÀAlder reactions catalyzed by Mikami×s [Ti{binol(2 À)}Cl 2 ] system, although the argument for single-point ligation in these cases is less clear. Recently, it was shown that a,b-unsaturated ketones, for which single-point ligation is obligatory, undergo DielsÀAlder addition to cyclopentadiene in the presence of a chiral imidazolidinone to give cycloadducts in moderate to high ee; however, the generality

Enantioselective Total Syntheses of (−)-Palau’amine, (−)-Axinellamines, and (−)-Massadines

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Studies on the regio- and diastereo-selective epoxidation of daphnanes and tiglianes

“…In 2002, White reported the formation of bromohydrins from silyl ether protected allylic alcohols using NBS/H 2 O in THF. 31 This procedure proceeds without deprotection and oxidation of the alcohol. To test this method, we prepared the C20-TBDPS PDBu 6 from phorbol in 4 steps (Scheme 2).…”

Enantioselective Access to Isoquinuclidines by Tropenone Desymmetrization and Homoallylic Radical Rearrangement: Synthesis of (+)-Ibogamine

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