Mark E. Welker

Unprecedented asymmetric induction from a chiral acetate enolate equivalent. The condensation of acetyl(triphenylphosphine)carbonyl-.eta.-cyclopentadienyliron [(.eta.-C5H5)Fe(CO)(PPh3)(Ac)] with imines

Diverses imines se condensent avec le diethyl-Al-enolate du racemique (η-C 5 H 5 )Fe(CO)(PPh 3 )COCH 3 en donnant des produits de condensation avec un bon rendement

Recent syntheses of PI3K/Akt/mTOR signaling pathway inhibitors.

This review focuses on the syntheses of PI3K/Akt/mTOR inhibitors that have been reported outside of the patent literature in the last 5years but is largely centered on synthetic work reported in 2011 and 2012. While focused on syntheses of inhibitors, some information on in vitro and in vivo testing of compounds is also included. Many of these reported compounds are reversible, competitive adenosine triphosphate (ATP) binding inhibitors, so given the structural similarities of many of these compounds to the adenine core, this review presents recent work on inhibitors based on where the synthetic chemistry was started, that is, inhibitor syntheses which started with purines/pyrimidines are followed by inhibitor syntheses which began with pyridines, pyrazines, azoles, and triazines then moves to inhibitors which bear no structural resemblance to adenine: liphagal, wortmannin and quercetin analogs. The review then finishes with a short section on recent syntheses of phosphotidyl inositol (PI) analogs since competitive PI binding inhibitors represent an alternative to the competitive ATP binding inhibitors which have received the most attention.

Preparation of 2-trialkylsiloxy- substituted 1,3-dienes and their diels-alder/cross-coupling reactions.

[reaction: see text] 2-Triethylsiloxy-substituted 1,3-butadiene has been prepared in gram quantities from chloroprene via a simple synthetic procedure. Silatrane and catechol-substituted analogues of this main group element substituted diene were prepared by ligand exchange and characterized by X-ray crystallography in addition to standard spectroscopic techniques. Diels-Alder reactions of these dienes are reported as well as subsequent TBAF assisted/Pd-catalyzed Hiyama cross-coupling reactions of those Diels-Alder adducts.

Preparation of (η5-cyclopentadienyl) and (η5-methylcyclopentadienyl) Fe(CO)2 Me cyclodextrin inclusion compounds and their subsequent ligand substitution reactions. Attempts at cyclodextrin mediated enantioselective ligand substitution

Two iron complexes, (η5-Cyclopentadienyl)Fe(CO)2Me and (η5-Methylcyclopentadienyl)Fe(CO)2Me, were prepared followed by their α, β, and γ cyclodextrin inclusion compounds. The included iron complexes participate in phosphine induced ligand substitution reactions under both thermal and photochemical conditions with no CO insertion/alkyl migration products observed in either case.

Preparation of 2-silicon-substituted 1,3-dienes and their Diels-Alder/cross-coupling reactions.

2-Triethoxysilyl-substituted 1,3-butadiene has been prepared in 30-g quantities from chloroprene via a simple synthetic procedure. Silatrane- and catechol-substituted analogues of this main group element substituted diene were then prepared on a 10-g scale by ligand exchange and characterized by X-ray crystallography in addition to standard spectroscopic techniques. 2-Dimethylphenylsilyl-1,3-butadiene has also been prepared from chloroprene on an 8-g scale. Diels-Alder reactions of these dienes are reported as well as subsequent TBAF-assisted/Pd-catalyzed Hiyama cross-coupling reactions of those Diels-Alder adducts. Silicon-substituted cycloadducts and cross-coupled products were also characterized by NMR spectroscopy and, in two cases, by X-ray crystallography.

Investigation of a transition metal-assisted retro Diels-Alder reaction used in the synthesis of transition metal S2O complexes

Abstract Treatment of 4,5-diphenyl-3,6-dihydro-1,2-dithiin-1-oxide with coordinatively unsaturated transition metal complexes resulted in the production of S2O complexes and 2,3-diphenylbutadien. A transition metal-assisted retro Diels-Alder mechanism has been proposed for this reaction. A series of IR and 1H NMR experiments and MNDO calculations on 4,5-diphenyl-3,6-dihydro-1,2-dithiin-1-oxide have been performed to gain additional information about this transformation.

Reactions of transition-metal η1-propargyl complexes with sulfur dioxide and sulfur trioxide: transition-metal–carbon bond cleaving reactions of the cycloadducts which yield 1,2-oxathiole-2-oxides and -2,2-dioxides

Abstract The preparation of several cyclopentadienyl iron dicarbonyl and triphenylphosphine manganese tetracarbonyl η1-2-alkynyl complexes are reported. The [3+2] cycloaddition reactions of these complexes with sulfur dioxide and sulfur trioxide yielded transition-metal substituted 1,2-oxathiolene-2-oxides and 1,2-oxathiolene-2,2-dioxides, respectively. One of the η1-propargyl complex SO3 cycloadducts has been characterized by X-ray crystallography. The transition metal can subsequently be cleaved from the oxathiole-oxide and dioxide containing complexes to produce a variety of new sulfur containing heterocycles.

Preparation of η1-1,3-dienyl, η1-1,2-dienyl and η3-cyclobutenone complexes via reactions of transition-metal carbonyl containing anions with allenic electrophiles

Abstract The preparation and reaction chemistry of 1,3- and 1,2-diene and related complexes derived from metal carbonyl containing anions and allenic electrophiles are addressed. The preparation of some CpFe(CO) 2 η 1 -diene complexes and their conversion into CpFe(CO) η 3 -diene complexes is presented followed by reactions of CpMo(CO) 3 − , CpW(CO) 3 − and CpMo(CO) 2 PR 3 − anions with allenic electrophiles which produce metal complexed cyclobutenones (via CO and alkene insertions from the initially formed product) and 1,2-diene complexes, respectively. Lastly, the reactions of PPh 3 (CO) 3 Co − anions with allenic electrophiles are outlined which result in several different coordination geometries depending on the reaction conditions used.

Preparation of substituted transition-metal (η1-propargyl complexes and their [3+2] cycloaddition reactions with sulfur dioxide and disulfur monoxide. Transition-metal–carbon bond cleaving reactions of the cycloadducts which yield oxathiolene oxides and dithiolene oxides

Abstract The preparations of several new cyclopentadienyl iron dicarbonyl η1-2-alkynyl complexes are reported. Their [3+2] cycloaddition reactions with sulfur dioxide and disulfur monoxide yielded transition-metal substituted 1,2-oxathiolene-2-oxides and 1,2-dithiolene-1-oxides, respectively. The transition-metal was cleaved from the oxathiolene-oxide and dithiolene-oxide containing complexes to produce new sulfur heterocycles.

Synthesis of 4-Aryl- and 4-Alkyl-2-silyl-1,3-butadienes and Their Diels−Alder/Cross-Coupling Reactions

An ene-yne cross methasis of silyl-substituted alkynes and alkenes has been developed as a route to 4-aryl- and 4-alkyl-2-silyl-substituted 1,3-dienes. The dienes prepared were used to affect highly diastereoselective Diels-Alder reactions and then the silicon-substituted Diels-Alder cycloadducts were used in Hiyama cross-coupling reactions. The cross-coupling reactions enable these silicon dienes to be used as synthons for a variety of other dienes one might prepare and need access to. Two of the silicon-substituted Diels-Alder cycloadducts and one of the Hiyama cross-coupling products were also characterized by X-ray crystallography.