The stereochemistry of freelingyne and the synthesis of dihydrofreelingyne

Ingham, CF; Massy-Westropp, RA

doi:10.1071/ch9741491

Cited by 26 publications

(6 citation statements)

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“…Finally, in order to compare the three methods of polyvinylogation used in this work (direct route : Scheme 2, path a, using KHMDS as base ; indirect routes : path b, then path c, via 5a or 5b), we have collected in Table 3 the 13 C NMR and mass spectroscopy. 1 H NMR data are in agreement with previous reports for 2a 18,19 and 2b. 18 Satisfactory microanalyses (C ± 0.4, H ± 0.31) or HRMS (± 0.006) obtained.…”

Section: Methodssupporting

confidence: 92%

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4-Diethoxyphosphonyl-2-methyl-1,3-dienolates and their O-Acylated and O-Silylated Derivatives: New, Efficient and Highly Stereoselective Polyvinylogation Reagents

Mohamed-Hachi¹

1999

Synthesis

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E)-4-Diethoxyphosphonyl-2-methylbut-2-enal was smoothly converted into its O-acetylated or O-triisopropylsilylated (E, E)-enol ethers, which were used as efficient and (E)-stereoselective five carbon polyvinylogation reagents of aldehydes, via the corresponding in situ generated potassium or tetrabutylammonium dienolates, respectively.The polyvinylogation reaction is a very attractive synthetic process in terpenoid chemistry. 1 For example, the direct insertion of a prenyl unit into the C=O bond of a carbonyl compound giving access to 3-methyl-substituted dienals has been widely used within the framework of retinoid synthesis. 2 In contrast, despite its synthetical significance, 3 the five carbon homologation of carbonyl compounds 1 into 2-methyl substituted dienals 2 (Scheme 1) is more rarely found : Wittig, 4,5 as well as HornerWadsworth-Emmons (HWE) 6 reagents 3a-c have been devised for this purpose. Except for 3b 5 , these reagents are phosphorus derivatives from protected 2-methylbut-2-enal, whose aldehyde function has to be regenerated at the end of the synthesis. Having recently proposed an efficient synthesis of (E)-4-diethoxyphosphonyl-2-methylbut-2-enal (3d), 7 we have now examined its use as a synthetic intermediate for C 5 polyvinylogation. Scheme 1In a preliminary study, we tested the efficiency of homologation of benzaldehyde with dienolate 4 prepared by deprotonation of 3d, the reaction being monitored by 31 P NMR (Scheme 2, path a). As expected, 3d [ 31 P NMR, d(CDCl 3 ) = 22.2] was readily converted by aqueous 4 N NaOH into its sodium salt 4 [M = Na, 31 P NMR, d(H 2 O) = 29.6], stable in water, which gave a moderate yield of 2a (R = Ph), under phase transfer catalysis (PTC) conditions (Table 1, Entry 1). A lower yield was obtained under solid/liquid PTC conditions (Entry 2). With KH in THF, the reaction required heating at 55°C (Entry 3), whereas t-BuOK converted 3d at 0°C into its potassium salt, which reacted slowly (Entry 4). A slightly better yield was obtained by use of KHMDS as a base (Entry 5). In the last three cases, the potassium salt was insoluble in THF and immediately agglomerated to a gummy pellet. Finally, the lithium dienolate 4 [M = Li ; 31 P NMR, d(THF) = 27.3], generated by deprotonation of 3d with LDA, was soluble in THF and reacted with benzaldehyde at -70°C giving 2a, but in modest yield (Entry 6). Scheme 2Downloaded by: Nanyang Technological University NTU. Copyrighted material.

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Section: Methodssupporting

confidence: 92%

“…1 H NMR data are in agreement with previous reports for 2a 18,19 and 2b. 18 Satisfactory microanalyses (C ± 0.4, H ± 0.31) or HRMS (± 0.006) obtained. b Determined on the crude product by 1 overall yields of the synthesis of aromatic dienals 2a-c, calculated from 3d.…”

Section: Methodssupporting

confidence: 92%

4-Diethoxyphosphonyl-2-methyl-1,3-dienolates and their O-Acylated and O-Silylated Derivatives: New, Efficient and Highly Stereoselective Polyvinylogation Reagents

Mohamed-Hachi¹

1999

Synthesis

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“…In Z vs. E isomers, these resonances were shifted upfield by about 0.5 ppm. [17] The highly unsaturated side-chain of dihydroxerulin (1) was prepared as shown in Scheme 5. Two 1,4-eliminations of HCl from the dichlorobutyne 14 gave the butadiyne dianion.…”

Section: Resultsmentioning

confidence: 99%

First Total Synthesis of Dihydroxerulin, a Potent Inhibitor of the Biosynthesis of Cholesterol

Siegel

Brückner

1998

Chem. Eur. J.

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Dihydroxerulin (1) is a noncytotoxic inhibitor of cholesterol biosynthesis. In spite of being achiral and devoid of OH groups, it was synthesized efficiently (12 steps, 6 steps in the longest linear sequence) from the optically active, polyhydroxylated sugar lactone 6. Our synthesis follows the strategy of Scheme 2 and illustrates with the b-elimination 10 3(Z)-9 a novel general approach to galkylidenebutenolides with stereopure C b C bonds. The enol triflate (Z)-9 was hydrogenolyzed to lactone (Z)-11 under very mild conditions. A Wittig reaction with the derived aldehyde (Z)-13 delivered 30 % of the title compound. Its 800 MHz 1 H NMR spectrum revealed that the C 8 C 9 bond of synthetic, and therefore also natural, 1 is trans-substituted.

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“…[10] Consequently, a large number of methods have been established for the synthesis of such molecules, [11] and they mainly rely on the intramolecular cyclization of complex acyclic precursors which may suffer from tedious multistep synthesis and purification. Undoubtedly, new protocols that can assemble the furan ring from simple chemicals are highly desirable.…”

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confidence: 99%

Gold‐Catalyzed C(sp³)H/C(sp)H Coupling/Cyclization/Oxidative Alkynylation Sequence: A Powerful Strategy for the Synthesis of 3‐Alkynyl Polysubstituted Furans

Zhang

Yang

et al. 2014

Angewandte Chemie

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In sharp contrast to the gold-catalyzed reactions of alkynes/allenes with nucleophiles, gold-catalyzed oxidative cross-couplings and especially CÀH/CÀH cross-coupling have been under represented. By taking advantage of the unique redox property and carbophilic p acidity of gold, this work realizes the first gold-catalyzed direct C(sp 3 ) À H alkynylation of 1,3-dicarbonyl compounds with terminal alkynes under mild reaction conditions, with subsequent cyclization and in situ oxidative alkynylation. A variety of terminal alkynes including aryl, heteroaryl, alkenyl, alkynyl, alkyl, and cyclopropyl alkynes all successfully participate in the domino reaction. The protocol offers a simple and region-defined approach to 3-alkynyl polysubstituted furans.

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The stereochemistry of freelingyne and the synthesis of dihydrofreelingyne

Cited by 26 publications

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4-Diethoxyphosphonyl-2-methyl-1,3-dienolates and their O-Acylated and O-Silylated Derivatives: New, Efficient and Highly Stereoselective Polyvinylogation Reagents

4-Diethoxyphosphonyl-2-methyl-1,3-dienolates and their O-Acylated and O-Silylated Derivatives: New, Efficient and Highly Stereoselective Polyvinylogation Reagents

First Total Synthesis of Dihydroxerulin, a Potent Inhibitor of the Biosynthesis of Cholesterol

Gold‐Catalyzed C(sp³)H/C(sp)H Coupling/Cyclization/Oxidative Alkynylation Sequence: A Powerful Strategy for the Synthesis of 3‐Alkynyl Polysubstituted Furans

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The stereochemistry of freelingyne and the synthesis of dihydrofreelingyne

Cited by 26 publications

References 0 publications

4-Diethoxyphosphonyl-2-methyl-1,3-dienolates and their O-Acylated and O-Silylated Derivatives: New, Efficient and Highly Stereoselective Polyvinylogation Reagents

4-Diethoxyphosphonyl-2-methyl-1,3-dienolates and their O-Acylated and O-Silylated Derivatives: New, Efficient and Highly Stereoselective Polyvinylogation Reagents

First Total Synthesis of Dihydroxerulin, a Potent Inhibitor of the Biosynthesis of Cholesterol

Gold‐Catalyzed C(sp3)H/C(sp)H Coupling/Cyclization/Oxidative Alkynylation Sequence: A Powerful Strategy for the Synthesis of 3‐Alkynyl Polysubstituted Furans

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Gold‐Catalyzed C(sp³)H/C(sp)H Coupling/Cyclization/Oxidative Alkynylation Sequence: A Powerful Strategy for the Synthesis of 3‐Alkynyl Polysubstituted Furans