Highly Regio- and Stereoselective Synthesis of (<i>Z</i>)-Trisubstituted Alkenes via Propyne Bromoboration and Tandem Pd-Catalyzed Cross-Coupling

Wang, Chao; Tobrman, Tomáš; Xu, Zhaoqing; Negishi, Ei‐ichi

doi:10.1021/ol901566e

Cited by 93 publications

(52 citation statements)

References 39 publications

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“…Unless an α-alkoxy ketone is involved 6 , Wittig-type transformations are minimally stereoselective 7,8 . Protocols for converting alkynes or carbonyl-containing compounds to trisubstituted alkenes entail lengthy sequences 9,10,11 , strongly acidic or basic conditions 10,11,12,13 , and/or just one stereoisomer 12,14 can be accessed (see the Supplementary Information, Section 1, for extended bibliography). The higher energy Z isomers can be obtained only if there is a suitable directing group 15,16 .…”

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confidence: 99%

Synthesis of E- and Z-trisubstituted alkenes by catalytic cross-metathesis

Nguyen

Koh

Mann

et al. 2017

Nature

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Catalytic cross-metathesis is a central transformation in chemistry, and yet, corresponding methods for stereoselectively generating acyclic trisubstituted alkenes in either isomeric form do not exist. The key problems are lack of chemoselectivity, namely, the preponderance of side reactions involving only the less hindered starting alkene, ensuing nonproductive processes of homo-metathesis byproducts, and formation of short-lived methylidene complexes. In contrast, in catalytic cross-coupling, another widely used process, substrates are more distinct and homocoupling is less of a problem. Here, we show that through cross-metathesis reactions involving E- or a Z-trisubstituted alkenes, easily prepared from commercially available starting materials by cross-coupling processes, many otherwise desirable and difficult-to-access linear E- or Z-trisubstituted alkenes can be synthesized efficiently and in exceptional stereoisomeric purity (up to >98% E or 95% Z). Utility is highlighted through concise stereoselective syntheses of biologically active compounds such as indiacen B (anti-fungal) and coibacin D (anti-inflammatory).

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confidence: 99%

Synthesis of E- and Z-trisubstituted alkenes by catalytic cross-metathesis

Nguyen

Koh

Mann

et al. 2017

Nature

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“…The residue was purified on silica gel column to afford S2 as a colorless oil (hexane−EtAc, yield: 3.9 g, 84%). 15 A mixture of 1.5 mol % of Pd 2 (dba) 3 (137 mg, 0.15 mmol), 6 mol % of AsPh 3 (184 mg, 0.6 mmol), and 15 mL of 1 M KOH(aq) in 50 mL of THF was cooled to 0°C before the addition of the compound S2 (2.9 g, 10 mmol). Then, a THF solution (10 mL) of trans- 16 or cis-1-iodo-1-hexene 17 (2.52 g, 12 mmol), which were synthesized according to the literature procedures, was added dropwise, and the reaction stirred for 30 min at room temperature.…”

Section: ■ Experimental Sectionmentioning

confidence: 99%

Palladium-Catalyzed Alkoxycarbonylation of Conjugated Enyne Oxiranes: A Diastereoselective Method for the Synthesis of 7-Hydroxy-2,3,5-trienoates

2015

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Palladium-catalyzed alkoxycarbonylative 1,5-substitution of conjugated enyne oxiranes provides a diastereoselective route to (E)-configured 7-hydroxy-2,3,5-trienoates. The reactions proceeded in a highly stereoselective manner, possibly through sequential formation of π-allylpalladium and σ-vinylallenyl palladium complexes. The major diastereomeric form of the product is determined by the configuration of the alkenyl moiety of the substrate. ■ INTRODUCTIONVinylallenes are, interestingly, reactive compounds toward various cycloaddition and cyclization reactions.1 They exhibit particularly higher activity and selectivity with Diels−Alder reactions, because their configurational equilibrium is more on the side of s-cis conformera prerequisite for a [4 + 2] cycloaddition reaction to occur effectivelythan for 1,3-dienes.2 In spite of their synthetic utility in organic reactions, there are only a few methods that can generate vinylallene structures. 1j,o,r,3 Recently, we introduced new methods for the construction of functionalized vinylallenes, which involved palladium-or rhodium-catalyzed reactions of carbonate or acetate derivatives of 2-en-4-yne alcohols. 4 2,3,5-Trienoates were a form of the vinylallene structure that was accomplished via palladiumcatalyzed alkoxycarbonylation of 2,4-enyne carbonates (Scheme 1). 4aIt was later found that in some cases, this reaction proceeds with high center-to-axial chirality transfer. Encouraged by these findings, we have decided to extend the methodology to enyne oxiranes in order to obtain more functionalized vinylallene structures. To the best of our knowledge, the only coupling method that involved the use of enyne oxiranes was their reactions with organocuprates, which led to alkyl-substituted vinylallenes that bear a hydroxyl group in the allylic position (Scheme 2).3e However, this method provided a very limited scope for both enyne substrates and their reacting partners, and moreover, the diastereoselectivity of this method, in terms of relative configuration of allenyl moiety and allylic carbon, could not be probed. We describe here for the first time that conjugated enynes carrying an oxirane moiety as a leaving group undergo

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“…However, γ-addition product 11 was found to be generated solely in 62 % yield. After several experiments, the desired α-addition product 12 was found to be produced with prenylzinc bromide, [25] but in only 14 % yield, with the major product still being the γ-addition product 11 (Table 1, entry 2, 55 % yield). As shown in Table 1, entry 3, prenylbarium bromide, [23] which is an excellent α-addition reagent, caused only decomposition even at -78°C.…”

Section: Resultsmentioning

confidence: 99%

“…Aldehyde 10: Synthesized from cyclohexanone in six steps including: (1) formylation, [35] (2) methylation, (3) LAH-mediated reduction, (4) p-methoxybenzylidene acetal formation, (5) DIBA-H mediated reduction of the acetal, and (6) Parikh-Doering oxidation. [36] To a stirred solution of the aldehyde 10 (37.5 mg, 0.143 mmol) in THF (1.0 mL) at -78°C, was added prenylzinc bromide [25] (0.4 m in THF, 0.72 mL, 0.286 mmol). After stirring for 30 min, the mixture was warmed to r.t. over 75 min.…”

Section: Alcoholmentioning

confidence: 99%

Asymmetric Synthesis and in vivo Biological Inactivity of the Right‐Hand Terpenoid Fragment of Terpendole E

Oikawa

Sasaki

2010

Eur J Org Chem

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Synthesis of the DEF‐ring terpenoid fragment of terpendole E, an Eg5 inhibitor, is described. The DE‐ring was constructed by a modification of Barrero's radical cyclization. The F‐ring tetrahydropyran was then constructed by acid‐induced cyclization of an epoxy alcohol, which was prepared by cross‐metathesis followed by Shi's epoxidation. Cell‐based assays indicated that the DEF‐ring fragment is not capable of inhibiting cell growth and cell cycle progression of human cancer cell lines, indicating that the DEF‐ring fragment alone is not sufficient for the biological activity.

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Highly Regio- and Stereoselective Synthesis of (Z)-Trisubstituted Alkenes via Propyne Bromoboration and Tandem Pd-Catalyzed Cross-Coupling

Cited by 93 publications

References 39 publications

Synthesis of E- and Z-trisubstituted alkenes by catalytic cross-metathesis

Synthesis of E- and Z-trisubstituted alkenes by catalytic cross-metathesis

Palladium-Catalyzed Alkoxycarbonylation of Conjugated Enyne Oxiranes: A Diastereoselective Method for the Synthesis of 7-Hydroxy-2,3,5-trienoates

Asymmetric Synthesis and in vivo Biological Inactivity of the Right‐Hand Terpenoid Fragment of Terpendole E

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