Diastereoselectivity of the conjugate addition of organocopper reagents to .gamma.-alkoxy .alpha.,.beta.-unsaturated carbonyl derivatives. Importance of the reagent type and the double-bond geometry

Yamamoto, Yoshinori; Chounan, Yukiyasu; Nishii, S.; Ibuka, Toshiro; Kitahara, Haruo

doi:10.1021/ja00046a008

Cited by 113 publications

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“…The adduct 8, obtained in 95% yield, revealed a dr of >15:1. 10,11 The final C-C bond forming reaction in the sequence was also highly diastereoselective. Alkylation of the potassium enolate of the ester 8 with allyl bromide gave the third contiguous stereogenic centre in 9 in 99% yield (dr > 20 :1).…”

Section: Methodsmentioning

confidence: 94%

A Synthesis of Mycalamide B

Kocieński¹,

Narquizian²,

Raubo³

et al. 1998

Synlett

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Mycalamide B, a potent antitumour agent, was synthesised from cheap, readily available starting materials: ethyl lactate, ethyl isobutyrate, 4-chlorobutanal, and 4-chlorobutanoyl chloride. The trioxabicyclo[4.4.0]decane ring system was created by reaction of a methoxymethyl ether with a silyloxyoxirane induced by phosphorus pentoxide.Mycalamides A 1 and B 2 were isolated from a sponge of the genus Mycale and shown to be potent inhibitors of tumour proliferation in a number of human tumour cell lines. 1,2 Total syntheses of mycalamides A and B have been reported by Hong and Kishi and elegant approaches to the various advanced fragments have been described by Nakata 3,4 , Roush 5,6 and Hoffmann 7,8 . We now report a synthesis of mycalamide B which shares the same fragment linkage strategy as our synthesis of 18-O-methylmycalamide B (Scheme 1). 9 However, the synthetic routes to the fragments 5 and 6 have been completely redesigned to offer greater flexibility, efficiency, and economy. Scheme 1The preparation of the 6-lithio-3,4-dihydro-2H-pyran 6 (Scheme 2) began by a diastereoselective conjugate addition of lithium dimethylcuprate to the ester 7 (Note 1) in the presence of TMSCl. The adduct 8, obtained in 95% yield, revealed a dr of >15:1. 10,11 The final C-C bond forming reaction in the sequence was also highly diastereoselective. Alkylation of the potassium enolate of the ester 8 with allyl bromide gave the third contiguous stereogenic centre in 9 in 99% yield (dr > 20 :1). Routine transformations accomplished the conversion of 9 to the alcohol 12 in preparation for the next critical step in the sequence, the inversion of configuration at C-2 (mycalamide numbering), which was plagued by competing elimination. However, the combination of trityl as the protecting group and p-chlorobenzoic acid as the nucleophile returned the nicely crystalline inverted ester 13 in 79% yield. Oxidative cleavage of the alkene followed by acid treatment achieved simultaneous trityl deprotection and lactonisation to give the second crystalline compound of the series, the lactone 15. The phenylselenide group in 16 was introduced by nucleophilic substitution of the butyrolactone. 12 Reductive cleavage of the p-chlorobenzoate in 16 (Note 2) returned a hydroxy acid which lactonised to 17 in 72% yield. Conversion of lactone 17 to the stannane 18 was accomplished by a 3-step sequence previously described in our synthesis of Pederin. 13 Dihydropyranone 25, a critical intermediate in the synthesis of the trioxabicyclo[4.4.0]decane ring system (Scheme 3), harbours a single stereogenic centre at C-15 which was constructed efficiently by two different routes. In the first route, the lithium enolate prepared from ethyl isobutyrate was condensed with 4-chlorobutanoyl chloride to give the β-keto ester 18 in 93% yield. Catalytic asymmetric hydrogenation 14-16 of the β-keto ester using [(R)-(+)-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl] chloro (p-cymene) ruthenium chloride installed the requisite (R)-configured stereogenic centre in good yield a...

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Section: Methodsmentioning

confidence: 94%

A Synthesis of Mycalamide B

Kocieński¹,

Narquizian²,

Raubo³

et al. 1998

Synlett

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“…Aldehydes 5-8, prepared in situ by the selective reduction of easily available esters [17] 1-4 using diisobutylaluminium hydride at -78°C, were selected as the starting carbonyl compounds. The precursor of the HWE reagent, ethyl 2-(diethoxyphosphoryl)-2-fluoroacetate (10), was prepared from chlorotrifluoroethene using our optimised synthetic protocol.…”

Section: Resultsmentioning

confidence: 99%

Synthesis of 3‐Fluorofuran‐2(5H)‐ones Based on Z/E Photoisomerisation and Cyclisation of 2‐Fluoro‐4‐hydroxybut‐2‐enoates

et al. 2007

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Mixtures of some (E)‐ and (Z)‐2‐fluoroalk‐2‐enoates prepared from the corresponding 2‐hydroxycarbonyl compounds and ethyl 2‐(diethoxyphosphoryl)‐2‐fluoroacetate have been transformed in high conversions into the target 3‐fluorofuran‐2(5H)‐ones by an efficient Z/E photoisomerisation of noncyclisable Z isomers followed by acid‐catalysed cyclisation. In contrast, the acid‐catalysed deprotection of ethyl (E)‐ and (Z)‐4‐[tert‐butyl(dimethyl)silyloxy]‐2‐fluoro‐4‐phenylbut‐2‐enoates resulted in the displacement of vinylicfluorine, affording ethyl (E)‐2‐oxo‐4‐phenylbut‐3‐enoate. 3‐Fluoro‐4‐phenylfuran‐2(5H)‐one was transformed into 2‐[tert‐butyl(dimethyl)silyloxy]‐3‐fluoro‐5‐methylfuran as a novel fluorinated building block.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

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Section: Methodsmentioning

confidence: 99%

“…It was shown that the corresponding cis-aziridinyl-methylene malonates produce predominantly the trans cyclopropane product. The stereochemical course of this MIRC reaction was explained [15] by invoking Yamamoto's model for conjugate additions of cyanocuprates to ␥-alkoxy-␣,␤-unsaturated esters [16].A convenient synthesis of methyl and unsubstituted aziridine-2-carboxylic esters makes use of the readily available amino acids serine (22a) and threonine (22b), respectively, as the starting material (Scheme 11) [18].The tritylated amino acids 23 are treated with two equivalents of methanesulfonyl chloride in the presence of triethylamine to produce 24 in good yields. This method of preparation has attracted High enantioselectivities were obtained for the reduction of acetophenone, comparable with those obtained with Corey's ␣,␣-diphenyl-2-pyrrolidinemethanol as the precatalyst [21].…”

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confidence: 99%

Synthetic potential of heteroatomic ring systems

Zwanenburg¹

1999

Pure and Applied Chemistry

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The synthesis of aziridine-2-carboxylic acid derivatives of high enantiopurity is described and their synthetic utility is discussed. Ring-opening and ring-expansion reactions of both oxirane and aziridine carboxylic esters are highlighted. Convenient syntheses of ␣-hydroxy, ␤-amino and ␣-amino, ␤-hydroxy carboxylic acids with defined stereochemistry are presented. The preparation of pyrrolidinone and azetidinone derivatives from functionalized three-membered heterocycles is described. Small-ring heterocycles also serve as the basis for the synthesis of catalysts, e.g. for an asymmetric reduction and for cyclopropanation reactions.Functionalized small-ring heterocycles are highly attractive compounds from the synthetic point of view [1]. Aziridine-2-carboxylic esters, for instance, are of interest as they are structurally related to ␣-as well as ␤-amino acids [2], and ring-opening reactions of oxiranecarboxylic acid derivatives allow the preparation of sterically defined ␣,␤-functionalized carboxylic acids. The strain present in these threemembered ring compounds ensures high reactivity in ring-opening and ring-expansion reactions [2]. We have developed a general and convenient synthesis of aziridine-2-carboxylic esters 1 from the corresponding oxiranecarboxylates 2 by successive treatment with sodium azide and triphenylphosphine [3]. The required starting materials in turn were prepared by Sharpless epoxidation of appropriate allylic alcohols [4], followed by oxidation of the 2,3-epoxy alcohols to the corresponding carboxylic acids using either ruthenium tetroxide or a two-step process involving a Swern oxidation and subsequent oxidation with sodium chlorite [3]. The sequence for the conversion of epoxy esters 2 into the aziridine esters 1 is depicted in Scheme 1.The treatment with sodium azide results in an S N 2-ring opening to give, in most cases, a mixture of regioisomeric azido alcohols 3. Without separation this mixture is treated with triphenylphosphine to give the aziridine esters 1 via the intermediacy of oxazaphospholidines 4 [5]. This formation of the threemembered ring by the Staudinger reaction proceeds with inversion at the oxygen-bearing carbon atom. Thus, in the overall process from 2 to 1 an inversion at the ␣ as well as the ␤ carbon atom takes place, with an excellent retention of chiral integrity. The procedure outlined in Scheme 1 has been utilized successfully for the synthesis of (þ)-(2S, 3S)-aziridine-2,3-dicarboxylic acid, a natural product isolated *Lecture presented at the 5th International Conference on Heteroatom Chemistry (ICHAC-5), London, Ontario, Canada, 5-10 July 1998, pp. 369-512.Correspondence: E-mail: zwanenb@sci.kun.nl Scheme 1from Streptomyces MD 398-A1 [6]. It is relevant to note that aziridinecarboxylic acids show the expected behavior for ␣-amino acids in reaction with triethylboron, viz. the formation of boroxazolidines 5 [7]. Regiocontrolled ring-opening reactions of aziridine esters were accomplished with, for instance, thiophenol and indole as the nucleophi...

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Diastereoselectivity of the conjugate addition of organocopper reagents to .gamma.-alkoxy .alpha.,.beta.-unsaturated carbonyl derivatives. Importance of the reagent type and the double-bond geometry

Cited by 113 publications

References 0 publications

A Synthesis of Mycalamide B

A Synthesis of Mycalamide B

Synthesis of 3‐Fluorofuran‐2(5H)‐ones Based on Z/E Photoisomerisation and Cyclisation of 2‐Fluoro‐4‐hydroxybut‐2‐enoates

Synthetic potential of heteroatomic ring systems

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