Synthesis of a potential intermediate for TMC-95A via an organocatalyzed aldol reaction.

N-Prolinylanthranilamide-based pseudopeptide organocatalyst 14 was shown to promote enantioselective direct aldol reaction of 7-iodoisatin and 2,2-dimethyl-1,3-dioxan-5-one with 90% conversion (75% isolated yield), 90% enantioselectivity, and 23:1 diastereoselectivity. To demonstrate the synthetic utility of this chemistry, the racemic aldol reaction product was converted in five steps to a potential intermediate for construction of the natural product TMC-95A.

Stereocontrolled intramolecular iron-mediated diene/vinyl ether cyclocoupling reactions.

A stereocontrolled intramolecular iron-mediated diene/olefin cyclocoupling reaction has been explored using vinyl ethers as the olefin partners. Spirolactams with functionalized (alkoxymethyl) side chains can be formed under thermal conditions. With a methoxy substituent on the diene, demetalation and hydrolysis of the cyclocoupling product afforded a single diastereomer.

N-Prolinylanthranilamide pseudopeptides as bifunctional organocatalysts for asymmetric aldol reactions.

Proline anthranilamide-based pseudopeptides were shown to be effective organocatalysts for enantioselective direct aldol reactions of a selection of aldehydes with various ketones with excellent yield, enantioselectivity up to 99% and anti to syn diastereoselectivity up to 25:1.

Diels-Alder reactions of cyclopentadienones with aryl alkynes to form biaryl compounds.

Diels-Alder reactions of cyclopentadienones, to afford substituted biaryls, were studied using an expanded substrate base. Electron-withdrawing groups on the aryl alkyne dienophile facilitated the reaction, and these substrates gave better yields than those with electron-donating substituents. Steric effects were also found to be important, and o,o'-dimethylphenylacetylene gave much poorer yield of biaryl product.

Studies toward the total synthesis of ristocetin A aglycone using arene-ruthenium complexes as S(N)Ar substrates: Construction of an advanced tricyclic intermediate.

Ruthenium-mediated S(N)Ar reactions are used to construct the diaryl ether linkages in two key intermediates for a projected total synthesis of the aglycone of ristocetin A.

1,5-Asymmetric induction during nucleophilic additions to arenetricarbonylchromium complexes: tricarbonyl(eta(6)-1-methyl-4-{spiro[(1R,2S)-1,7,7-trimethylbicyclo[2.2.1]heptane-3,2'-1,3-dioxolan]-2-yloxy}benzene)chromium.

The tricarbonylchromium unit bound to the arene ring of the chiral title complex, [Cr(C(19)H(26)O(3))(CO)(3)], is rotated by ca 25 degrees in agreement with the proposed mechanism for 1,5-asymmetric induction of nucleophilic attack.

Synthesis of a key precursor for orienticin C and model study on ruthenium-mediated macrocyclization.

A tripeptido--arene--ruthenium complex was prepared as a key precursor for the projected synthesis of orienticin C, demonstrating that the cyclopentadienylruthenium moiety can be attached to a chloroarene in the presence of multiple functionality. The ruthenium-mediated intramolecular SNAr reaction for formation of the required diaryl ether linkage was successfully tested on a model system.

An iron-promoted aldehyde-diene cyclocoupling reaction.

A stereospecific intramolecular iron tricarbonyl-promoted aldehyde-diene cyclocoupling reaction was investigated by using simple substrates 6 and more complicated substrates 30a/30b. Demetalation of the initial products converts all complexed dienes to their pure organic counterparts. In addition, the nickel-catalyzed carbonyl-ene reaction and the Prins reaction were investigated with two different substrates.

Dynamic diastereoselectivity during iron carbonyl mediated spirocyclization reactions.

Dynamic diastereoselectivity during Fe(CO)3 promoted [6+2] ene spirocyclization of 35a and 35b, having a chiral center on the pendent side chain, was investigated and gave rise to products 28a and 28b instead of four possible isomers. From this reaction, two chiral centers are generated, with absolute stereochemistry determined by the double bond geometry and the chiral center already present. 28a/b and the diene product from demetallation of 28a are proposed as potential intermediates for total synthesis of 18-deoxycytochalasin H.

Hydroxyl-directed conjugate additions of carbon nucleophiles to cyclopentadienones.

[Structure: see text] The conjugate additions of different carbon nucleophiles to cyclopentadienone substrates (1 and 2) with one free hydroxyl functional group were investigated to determine the role of the hydroxyl group in controlling regiochemistry. During this reaction an unexpected intramolecular displacement of OTBS by the enolate intermediate occurs, to afford cyclopropane derivatives.

Iron tricarbonyl stabilized pentadienyl cation as initiator for cascade polycyclizations: a diastereoselective entry into octahydrophenanthrenes.

A new example is provided of completely diastereoselective polycyclization, affording the octahydrophenanthrene framework. Generation of an iron tricarbonyl stabilized pentadienyl carbocation is the triggering event of the cascade reaction. The carbocation is generated by anchimerically assisted regiospecific protonation of a double bond adjacent to the iron tricarbonyl diene moiety.

Intramolecular iron-mediated diene/olefin cyclocoupling: formation of carbon spirocycles.

[reaction: see text] A short and convenient diastereoselective synthesis of all-carbon spirocylic molecules was developed. A straightforward protocol that involves rearrangement of the diene-Fe(CO)(3) complex followed by cyclization delivers the desired product. The reaction substrates were easily prepared by reaction of an appropriate nucleophile and a cyclohexadienyl-Fe(CO)(3) cation.

Vicinal stereocontrol during nucleophilic addition to arene chromium tricarbonyl complexes: formal synthesis of (+/-)-erythro Juvabione.

[reaction: see text] Vicinal stereocontrol during nucleophilic addition of tert-butyl lithiopropionate to eta(6)-anisole chromium tricarbonyl complexes with differing para substituents has been studied. Excellent vicinal double stereoinduction (>99:1) was observed when the para substituent was Si(CH(3))(3), and this has been applied to a stereoselective formal synthesis of (+/-)-erythro Juvabione. Asymmetric synthesis by chiral auxiliary directed nucleophilic addition is also discussed.

A convenient one-pot procedure to afford bicyclic molecules by stereospecific iron carbonyl mediated [6 + 2] ene-type cyclization: a possible approach to gelsemine.

A convenient one-pot procedure to prepare angularly substituted bicyclic and tricyclic molecules with excellent diastereoselectivity in good yield was developed, by Fe(CO)5 promoted cyclization. Three transformations (complexation, isomerization, and cyclization) were realized in a single operation. The product of this reaction may be a precursor for synthesis of the alkaloid gelsemine.

Conjugate additions of carbon nucleophiles to cyclopentadienones.

[reaction: see text] Reactions of cyclopentadienones 1 with alkylmagnesium bromides were investigated and gave 1,4 adduct and/or 1,2 adduct.

Fluorescence and NMR binding studies of N-aryl-N'-(9-methylanthryl)diaza-18-crown-6 derivatives.

N-Aryl-N'-(9-methylanthryl)diaza-18-crown-6 derivatives perform as fluorescent photoinduced electron-transfer (PET) sensors with very selective response toward Ca(2+) versus Mg(2+), Na(+), and K(+). The fluorescence intensity was increased by a factor of up to 170 in the presence of Ca(ClO(4))(2). (1)H NMR studies show that metal cations affect these molecules very differently: Ca(2+) has a global effect on each molecule, while Mg(2+) affects part of each molecule, and K(+) and Na(+) affect each molecule moderately, which is very consistent with the fluorescence response.

Fluorescent photoinduced electron transfer (PET) sensing molecules with p-phenylenediamine as electron donor.

Fluorescent photoinduced electron-transfer sensors were made from p-phenylenediamine-substituted azacrown ethers attached with a dansyl group, in which the p-phenylenediamine moiety serves as electron donor and the dansyl group acts as the acceptor. Chelation-enhanced fluorescence was observed upon addition of metal salts. Selective fluorescence response was observed for Mg(2+) and/or Ca(2+) versus Na(+) and K(+) due to size match and charge density sensitivity of the p-phenylenediamine moiety.

Preparation of N-aryl azacrown ether derivatives, using arene-iron chemistry.

m- or p-phenylenediamine and m- or p-chlorophenyl-substituted azacrown ether derivatives were synthesized through sequential nucleophilic substitution of [(eta(5)-cyclopentadienyl)(eta(6)-(m- or p-dichlorobenzene))]iron hexafluorophosphate by azacrown ethers and cyclohexaamines. Monoarylation is the main reaction for diazacrown ethers. The overall yield from the starting complex is 50-96% for multiple steps.

Double cyclization via intramolecular coupling between cyclohexadiene-Fe(CO)3 complexes and pendant conjugated dienes.

Intramolecular double cyclization between a cyclohexadiene-Fe(CO)3 complex and a pendant diene yielded a tricyclic molecule containing a spirocenter, with defined relative stereochemistry of four contiguous carbon centers. The nature of the substituent on the pendant diene moiety has a significant effect on the yield: an ester group leads to lower yield. The product has a conjugated cyclohexadiene or methoxycyclohexadiene system; the latter was converted to an enone.

A new paradigm for cationic cyclization of iron tricarbonyl diene complexes with pendant alkenes and arenes.

A new example of stereospecific cationic cyclization of iron tricarbonyl diene complexes with pendant alkenes and arenes is provided. Protonation of a double bond vicinal to the iron tricarbonyl diene moiety is employed to trigger the cyclization, rather than the previously reported Lewis/protic acid dehydroxylation of diastereomeric alcohols, eliminating one step of separation and avoiding some reactivity problems previously encountered for one of the alcohol diastereoisomers. [reaction: see text]

Silicon-tethered cyclocarbonylation of alkynes.

[reaction: see text] Temporary union of alkynes in the Fe(CO)5-promoted cyclocarbonylation provides a method for carbonylative cross-coupling of alkynes to construct unsymmetrically substituted cyclopentadienones.

Diastereoselective conjugate additions to pi-allylmolybdenum complexes: a stereocontrolled route to 3,4,5-trisubstituted gamma-butyrolactones.

[reaction: see text] pi-Allylmolybdenum complex 6b is obtained as a single isomer by Knoevenagel condensation of aldehyde 1 with Meldrum's acid. Conjugate additions of Grignard reagents to Meldrum's acid alkylidene derivative 6b are shown to be completely diastereoselective. Further functional group transformation of the 1,4-adducts, followed by demetalation, leads to trisubstituted tetrahydrofurans and gamma-butyrolactones.

Lateral Stereocontrol Using pi-Allylmolybdenum Systems: The Use of Methyl Substitution To Effect Conformational Control Leading to High Levels of Stereoselectivity.

Stereocontrol exerted by a pi-allyl-Mo(CO)(2)Tp system (Tp = hydrotris(1-pyrazolyl)borato), during addition of Grignard reagents to neighboring aldehyde functionality and during dihydroxylation of alkenes, is found to be dependent on conformational preferences of the substituent relative to the organometallic moiety. Incorporation of a methyl group at C(2) of the pi-allyl ligand leads to excellent conformational control when the lateral substituent is a vinyl group, and this results in a diastereomer ratio of 25:1 for the diol that is obtained from osmylation. Poorer conformational control is observed for an aldehyde, and nucleophile additions show correspondingly lower stereoselectivity.

Asymmetric Conversion of Arenechromium Complexes to Functionalized Cyclohexenones: Progress toward Defining an Optimum Chiral Auxiliary.

An investigation into the asymmetric synthesis of 5-substituted cyclohexenones via nucleophile addition to (alkoxyarene)chromium tricarbonyl complexes is described. Diastereoselectivity during the nucleophile addition step was achieved using alkoxy substituents derived from terpenoid substrates as chiral auxiliaries. Selectivities as high as 24:1 were obtained when 2-phenylisoborneol was used as the chiral auxiliary and as high as 17:1 using 3,3-(ethylenedioxy)isoborneol.