Mono-and 2,2′-di-substituted terminal alkenes can be isomerized into the more stable internal Zand E-alkenes by treating them with catalytic amounts of [(allyl)PdCl] 2 or [(allyl)NiBr] 2 , a triarylphosphine and silver triflate at room temperature. The isomeric ratio (E:Z) depends on the alkenes, the (E)-isomer being the major one. The reaction is tolerant to a wide variety of functional groups including other reactive olefins. Unlike the more reactive Ir catalysts, monosubstituted alkenes give almost exclusively the 2-alkenes. Direct comparison to two of the best-known catalysts for this process, (Ir(PCy 3 ) 3 ] + [BPh 4 ] − , and Grubbs Generation II metathesis catalyst) is also reported.

Imprinted polymers were prepared using a functional monomer derived from boronophthalide and a number of steroid templates bearing spatially separated hydroxyl groups. The cooperative nature of the binding interaction was demonstrated in polymers imprinted with androst-5-ene-3β,17β-diol and its structural analogues. The stoichiometry and kinetics of binding were probed using IR spectroscopy, selective solvent extractions, and chemical modification experiments. The feasibility of using imprinted polymers as reusable protecting groups was established by the regioselective acylation of trihydroxysteroids bound to polymers imprinted with structurally related diols. In polymers prepared with tert-butyl ester templates “matched” to the substrate, regioselectivities as high as 23.1:1 (24-acetate:3-acetate) in the monoester products (65% of recovered material) were seen. In the “unmatched” case, the ratio fell to 5.4:1; however, in functionally identical control polymers, imprinted with ethylene glycol, the regioselectivity was completely reversed (<1:100), and only poor yields of monoesters (13%) were obtained.

Benzophenone Iodine 3,5‐Bis(trifluoromethyl)bromobenzene Sodium tetrafluoroborate Bis[1,2:5,6‐eta‐(1,5‐cycloocatadiene)nickel Allyl bromide Ethylene n ‐Butyllithium Methyltriphenylphosphonium bromide Triphenylphsophine oxide Sodium tetrakis[(3,5‐trifluoromethyl)phenyl]borate Di‐(mu‐bromo)bis(eta‐allyl)nickel(II) 2‐Phenyl‐1‐butene ( R )‐3‐Methyl‐3‐phenylpentene

Fine tuning of the biaryl and amino moieties of Feringa's phosphoramidite ligands yields structurally simpler, yet more efficient and selective, ligands for asymmetric hydrovinylation of vinylarenes and acylic 1,3-dienes. The enantioselectivities and yields observed in the formation of the 3-arylbutenes are among the highest for all asymmetric catalytic processes reported to date for the synthesis of intermediates for the widely used antiinflammatory 2-arylpropionic acids including naproxen, ibuprofen, fenoprofen, and flurbiprofen.The asymmetric hydrovinylation (HV) of an alkene, viz., addition of ethylene as a vinyl group and a hydrogen across a double bond with concomitant generation of an asymmetric center, is one of the oldest asymmetric carbon-carbon bond-forming reactions. 1 Since ethylene is a cheap, abundantly available feedstock carbon source, and the resulting vinyl group in the product readily transformed into a variety of other common functional groups, this reaction has huge potential as a scalable, environmentally benign method for the preparation of valuable chemical intermediates.Recently, several protocols for the reaction have been described in which nearly quantitative yields of the desired products can be obtained using only catalytic amounts of metal complexes, most notably those of nickel (eq 1). 2 Yet, practical levels of enantioselectivity (i.e., enantiomeric excess >95%) have been achieved only for limited substrates, often at the cost Conspicuously absent among the more successful substrates are Ar-substituted vinylarenes, best exemplified 3 by 4-isobutylstyrene (current best: ∼95% yield, 91% ee) and 6-methoxy-2-vinylnaphthalene (73% yield; 86% ee), potential precursors of antiinflammatory 2-arylpropionic acids, (S)-ibuprofen and (S)-naproxen, the latter a hugely successful commercial drug (Aleve) currently produced by classical resolution. 4 Since binaphthol-derived phosphoramidites 5 were introduced for asymmetric HV of vinylarenes, 6a under our originally reported conditions, 2a these ligands have been used with varying degree of success for HV of a variety of substrates including norbornene, 6b 1,3-dienes, 6c and 1-substituted styrenes. 6d,e Asymmetric HV of similar substrates is the starting point for several total synthesis efforts (e.g., pseudopterosins and related compounds (see eq 1)) in our group; therefore, we decided to explore the scope of ligand tuning in this highly versatile, modular ligand system, and the results are reported in this paper. Ligands L 1 -L 10 (Figure 1), readily prepared 7,8 from the corresponding bisphenols, PCl 3 , and various chiral amines, were used for this study.The feasibility of ligand control in the hydrovinylation was initially investigated using pmethoxystyrene, an electron-rich model substrate that consistently had given one of the poorest reactions (80% yield, 73% ee) among vinylarenes tested previously. We started these investigations using a modified protocol (eq 1, R = 4-OMe) that had originally been developed for the generation o...

Aryl bromides and iodides in the presence of catalytic amounts of a palladacycle derived from acetophenone oxime and 2 equivalents of potassium acetate react with ethylene under ambient pressure (15-30 psi) to give the corresponding vinylarenes. The reactions work with both electrondeficient and electron-rich aryl compounds and tolerate wide variety of common functional groups. Vinyl bromides lead to 1,3-dienes in moderate yields.

Abstract1,3-Dienes derived from steroidal D-ring C 17 -ketones undergo Ni(II)-catalyzed hydrovinylation to give 1,2-or 1,4-addition of ethylene. Using finely tuned phosphoramidite ligands it is possible to synthesize either the C 20 (R)-or the C 20 (S)-derivatives without mutual contamination. The proportion of the 1,4-adduct, which is also formed stereoselectively, can be minimized by optimizing the reaction conditions. Since the two alkenes in the resultant dienes have differing steric demands for many potential reactions, and are ideally juxtaposed for further D-ring functionalization, these intermediates could be useful for the preparation of biologically important compounds such as vitamin D analogs and various antitumor steroidal glycosides.

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A three-step procedure for the synthesis of 2-arylpropionic acids (profens) from vinyl arenes in nearly enantiomerically pure form has been developed. Excellent yields (>97%), regioselectivities (>99%), and enantioselectivities (>97% ee) for the desired branched products were obtained in the asymmetric hydrovinylation reactions of vinyl arenes, and the products from these reactions were transformed into 2-arylpropionic acids via oxidative degradation. Subsequent Curtius or Schmidt rearrangements of these acids provided highly valued 1-arylethyl amines, including a prototypical primary amine with an α-chiral tertiary N-alkyl group, in very good yields.