Single isomer trisubstituted olefins bearing alkyl groups

E-β-Chloro-α-iodo-α,β-unsaturated esters were converted to single isomer trisubstituted olefins bearing alkyl substituents by using and alkyl-Suzuki cross coupling. The process was highly selective, and the products in all cases were isolated as single isomers. Mechanistic investigations indicated that this process transfers a hydrogen from water to the α-position of the substrate, and then an alkyl group is introduced to the β-position of the intermediate template while replacing a chloride.     

Highly diastereoselective generation of various 3,3-disubstituted allyl boronates for the stereospecific construction of quaternary centers

Single isomer trisubstituted olefins were converted into allyl boron nucleophiles that were condensed with aldehydes to give products containing quaternary centers. The products were obtained in extremely high diastereomeric ratios, a reflection of the stereochemical integrity of the starting materials.     

大位阻烯烃不对称环氧化合成手性环氧化合物

采用大位阻的有机锂试剂或格氏试剂与卤代烯烃偶联合成了7种大位阻取代烯烃. 以Oxone(KHSO₅)作为氧化剂, 分别在D-果糖衍生酮和(2S,5R)-2-异丙基-5-甲基环己酮为催化剂的催化下, 将合成的7种大位阻取代烯烃转变成了7个大位阻的手性环氧化合物. 其中以D-果糖衍生酮的对映选择性最好, 当双键碳上含有3个取代基时, 对映选择性最高, e.e.值为96.8%~99.5%. (2S, 5R)-2-异丙基-5-甲基环己酮的对映选择性较差, 无论是一取代的烯烃还是三取代的烯烃, 其e.e.值均介于25.6%~34.1%之间.     

Single-isomer trisubstituted olefins from a novel reaction of (E)-beta-chloro-alpha-iodo-alpha,beta-unsaturated esters and amides

(E)-beta-chloro-alpha-iodo-alpha,beta-unsaturated esters are converted to single isomer trisubstituted olefins bearing three different carbon substituents by cross-coupling under reflux. Mechanistic investigations suggest that this process transfers a hydrogen from the boronic acid to the alpha-position of the substrate and then introduces an aryl group to the beta-position of the intermediate template while replacing chloride. The reaction is highly stereoselective, showing preference for the E-isomer. The process proceeds through (E)-beta-chloro-alpha-aryl-alpha,beta-unsaturated esters that are transformed efficiently into the corresponding E-products through stereoselective Suzuki-type reactions giving single isomers. The observed stereochemistry is apparently enabled by the intermediacy of a palladium allenoate. The reaction involves a catalytic cycle in which Pd(II) is reduced to Pd(0) through the formation of biaryl-coupled products.     

Stereoselective Synthesis of Trisubstituted Olefins

Abstract

A new method for the highly stereoselective synthesis of trisubstituted olefins is. presented. The method involves the stereoselective construction of various β-hydroxy phosphonamidates followed by their thermolysis to provide trisubstituted olefins in extremely high geometrical purity (>99/1).     

Stereoselective synthesis of trisubstituted olefins by a directed allylic substitution strategy

New methodology for the stereoselective synthesis of trisubstituted olefins is presented. The use of ortho-diphenylphosphanyl benzoate (o-DPPB) as a directing leaving group for copper-mediated allylic substitution with Grignard reagents allowed for the stereoselective construction of a wide range of E olefins, without the need for an adjacent electron-withdrawing group. Our modular three-step approach toward trisubstituted alkenes commenced with geminal α-methylene aldehydes. Addition of an organometallic reagent and introduction of the o-DPPB group by esterification was followed by the o-DPPB-directed copper-mediated allylic substitution with a Grignard reagent to furnish stereodefined trisubstituted olefins. Additionally, incorporation of a stereocenter from the chiral pool allowed the preparation of an enantiomerically pure olefin that bore three alkyl substituents in high E/Z selectivity.     

Highly enantioselective cyclopropanation of trisubstituted olefins

A highly efficient asymmetric cyclopropanation of trisubstituted olefins with methyl diazoacetate has been developed in terms of an elaborate modified chiral bisoxazoline/copper complex as a catalyst. A broad scope of substrates is compatible with this catalyst system, including various trisubstituted olefins bearing different aryl-, fused aryl- and alkyl-substituents, providing an easy access to optically active 1,1-dimethyl cyclopropanes in good yields with excellent diastereo- and enantio-selectivity.     

Development of new thiazole-based iridium catalysts and their applications in the asymmetric hydrogenation of trisubstituted olefins

New thiazole-based chiral N,P-ligands that are open-chain analogues of known cyclic thiazole ligands have been synthesized and evaluated in the iridium-catalyzed asymmetric hydrogenation of trisubstituted olefins. Chirality was introduced into the ligands through a highly diastereoselective alkylation using Oppolzer's camphorsultam as chiral auxiliary. In general, the new catalysts are as reactive and selective as their cyclic counterparts for the asymmetric hydrogenation of various trisubstituted olefins.     

Regioselective hydroformylation of allylic alcohols

A highly regioselective hydroformylation of allylic alcohols is reported toward the synthesis of β-hydroxy-acid and aldehyde products. The selectivity is achieved through the use of a ligand that reversibly binds to alcohols in situ, allowing for a directed hydroformylation to occur. The application to trisubstituted olefins was also demonstrated, which yields a single diastereomer product consistent with a stereospecific addition of CO and hydrogen.     

Palladium-catalyzed double arylations of terminal olefins in acetic acid

A palladium-catalyzed Heck diarylation of terminal olefins under ligand-free conditions in acetic acid is described. This procedure allows double arylation of terminal olefins affording trisubstituted olefins in good to excellent yields. The methodology is applicable to the coupling of both electron-deficient and electron-rich aryl iodides leading to symmetrical and unsymmetrical β,β-diarylated alkenes.     

Rhodium fluorapatite catalyst for the synthesis of trisubstituted olefins via cross coupling of Baylis-Hillman adducts and arylboronic acids

Treatment of fluorapatite (prepared by incorporating basic species F(-) in apatite in situ by coprecipitation) with an aqueous solution of RhCl(3) resulted in rhodium-exchanged fluorapatite catalyst (RhFAP), which successfully promoted cross coupling of Baylis-Hillman adducts with arylboronic acids to yield trisubstituted olefins. A variety of arylboronic acids and Baylis-Hillman adducts were converted to the corresponding trisubstituted olefins, demonstrating the versatility of the reaction. The reaction is highly stereoselective. RhFAP was recovered quantitatively by simple filtration and reused with almost consistent activity.     

Configurations and conformations in acyclic,unsaturated hydrocarbons. A 13C NMR study

¹³C NMR (CMR) spectra of a number of di- and trisubstituted ethylenes have been measured. Very consistent values are found for the differential shieldings of allylic carbons in a number of linear, (Z)- and (E)-disubstituted ethylenes. The discrepancies between the several structural elements are explained tentatively by assuming different rotational preferences in the (Z)-isomers, the (E)-isomers, or both. The results obtained for some branched olefins are qualitatively in agreement with conclusions reached in previous ¹H NMR (PMR) investigations, with the possible exception of 2,5-diMe-3-hexene. Differential shieldings in trisubstituted ethylenes are larger than in disubstituted ethylenes, probably as a consequence of steric interaction between geminal substituents. It is confirmed, that API's recent relabelling of the isomers of 3-Me-2-hexene was justified. Furthermore, the (E)-configuration is assigned to the high-boiling isomer of 3,4,4-triMe-2-pentene. On the other hand, the high-boiling isomer of 3-Et-4-Me-2-pentene is shown to be the (Z)-isomer. For the isomeric pair of geraniol and nerol, the (E)-configuration is assigned to the former and the (Z)-configuration to the latter, in agreement with our recent PMR investigations.     

C3‐Symmetric Trisimidazoline‐Catalyzed Enantioselective Bromolactonization of Internal Alkenoic Acids

A method for conducting enantioselective bromolactonization reactions of trisubstituted alkenoic acids, using the C₃‐symmetric trisimidazoline 1 and 1,3‐dibromo‐5,5‐dimethyl hydantoin as a bromine source, has been developed. The process generates chiral δ‐lactones that contain a quaternary carbon. The results of studies probing geometrically different olefins show that (Z)‐olefins rather than (E)‐olefins are favorable substrates for the process. The method is not only applicable to acyclic olefin reactants but can also be employed to transform cyclic trisubstituted olefins into chiral spirocyclic lactones. Finally, the synthetic utility of the newly developed process is demonstrated by its application to a concise synthesis of tanikolide, an antifungal marine natural product.     

Stereoselective Synthesis of Trisubstituted Vinylboronates from Ketone Enolates Triggered by 1,3‐Metalate Rearrangement of Lithium Enolates

An unprecedented stereoselective synthesis of trisubstituted vinylboronates is reported to proceed by direct borylation of lithium ketone enolates under transition‐metal‐free conditions. The stereospecific C?O borylation of lithium enolates was triggered by a carbonyl‐induced 1,3‐metalate rearrangement via a C‐bound boron enolate. DFT calculations and control experiments revealed that the stereoselectivity is controlled by sterics. A variety of stereospecific trisubstituted vinylboronates, together with several tetrasubstituted vinylboronates, were conveniently synthesized with the newly developed methodology. Based on the transformation of stereospecific vinylboronate, a single isomer of Dienestrol was efficiently obtained.     

Practical synthesis of an L-fructose-derived ketone catalyst for asymmetric epoxidation of olefins

An L-fructose-derived ketone catalyst for asymmetric epoxidation of trans- and trisubstituted olefins was efficiently prepared from L-sorbose in five steps.     

手性酮催化的烯烃不对称环氧化反应

手性酮是催化非官能化烯烃不对称环氧化的一类重要催化剂 ,它与过氧硫酸氢钾可原位产生对贫电子和富电子烯烃均很有效的氧化剂———手性二氧杂环丙烷 .综述了各种结构的手性酮在反式烯烃、三取代烯烃和顺式烯烃等的不对称环氧化反应中的应用研究进展 ,总结了手性酮结构及反应条件对其催化活性和不对称诱导作用的影响     

Conversion of ketones to trisubstituted olefins under neutral conditions

Phenylaziridine hydrazones react at 140°–160°C to provide sterically congested trisubstituted olefins in good yield.     

Addition of benzylzinc halides to alkenyl(phenyl)iodonium triflates: stereoselective synthesis of trisubstituted alkenes

Benzylic organozinc reagents generated by insertion of zinc metal into benzyl-bromine bonds react with alkenyl(phenyl)iodonium triflates to provide single stereoisomers of trisubstituted olefins. The extremely high reactivity of the phenyliodonio moiety allows these reactions to be performed in the absence of copper salts or palladium catalysts. The reaction is performed from -40 degrees C to room temperature in THF. Excellent yields of the desired cross-coupled products have been obtained despite the occurrence of a competing electron-transfer-induced fragmentation.     

Synthesis of Unsaturated Nitriles from Trisubstituted Olefins Via Ene-Type Chlorination

Unsaturated nitriles have been synthesized from trisubstituted olefins via ene-type chlorination and regioselective substitution with cyanide ion followed by double bond migration.     

C3-symmetric trisimidazoline-catalyzed enantioselective bromolactonization of internal alkenoic acids

A method for conducting enantioselective bromolactonization reactions of trisubstituted alkenoic acids, using the C(3)-symmetric trisimidazoline 1 and 1,3-dibromo-5,5-dimethyl hydantoin as a bromine source, has been developed. The process generates chiral δ-lactones that contain a quaternary carbon. The results of studies probing geometrically different olefins show that (Z)-olefins rather than (E)-olefins are favorable substrates for the process. The method is not only applicable to acyclic olefin reactants but can also be employed to transform cyclic trisubstituted olefins into chiral spirocyclic lactones. Finally, the synthetic utility of the newly developed process is demonstrated by its application to a concise synthesis of tanikolide, an antifungal marine natural product.