Salvatore D. Lepore

Selective One-Pot Synthesis of Allenyl and Alkynyl Esters from β-Ketoesters

A convenient method is described for the dehydration of beta-ketoesters to generate conjugated and deconjugated alkynyl esters and conjugated allenyl esters. This sequential one-pot method involves the formation of a vinyl triflate monoanion intermediate that leads to the selective formation of alkynes or allenes depending on additives and conditions used. Product outcomes appear to be a function of unique mono- and dianion mechanisms which are described.

Catalytic synthesis of nonracemic azaproline derivatives by cyclization of β-alkynyl hydrazines under kinetic resolution conditions.

Cyclic addition of a hydrazine nitrogen to unactivated alkynes catalyzed by non-metals. Starting from readily accessible γ-silyl allenyl esters, β-alkynyl hydrazines are prepared in one step and subsequently undergo unprecedented cyclization reactions in the presence of ammonium and phosphonium catalysts leading to dehydro-azaproline products. These heterocycles are also produced in high enantiomeric excesses using chiral ammonium phase transfer catalysts via a kinetic resolution pathway.

Nucleophile assisting leaving groups: a strategy for aliphatic 18F-fluorination.

A series of arylsulfonate nucleophile assisting leaving groups (NALGs) were prepared in which the metal chelating unit is attached to the aryl ring via an ether linker. These NALGs exhibited significant rate enhancements in halogenation reactions using metal halides. Studies with a NALG containing a macrocyclic ether unit suggest that rate enhancements of these nucleophilic halogenation reactions are facilitated by stabilization of charge in the transition state rather than through strong precomplexation with metal cation. In several cases, a primary substrate containing one of the new leaving groups rivaled or surpassed the reactivity of triflates when exposed to nucleophile but was otherwise highly stable and isolable. These and previously disclosed chelating leaving groups were used in (18)F-fluorination reactions using no-carrier-added [18F]fluoride ion (t(1/2) = 109.7 min, beta+ = 97%) in CH3CN. Under microwave irradiation and without the assistance of a cryptand, such as K2.2.2, primary substrates with select NALGs led to a substantial improvement (2-3-fold) in radiofluorination yields over traditional leaving groups.

Zinc(II) catalyzed conversion of alkynes to vinyl triflates in the presence of silyl triflates.

The conversion of alkynes to their corresponding vinyl triflates in the presence of stoichiometric TMS-triflate was greatly facilitated by the triflate salt of several transition metal catalysts most especially Zn(OTf)2. Products are formed in high regioselectivity under mild conditions. Internal alkynes bearing an aryl substituent afford vinyl triflates with a modest preference for the Z-isomer especially with larger substituents. A mechanism is put forward to explain the unique role of silicon in this system.

Anion Catalyzed Addition of γ-Silylallenyl Esters to Aldehydes: A New Entry into [3.2.1] Bicyclic Natural Products

A significant improvement in the generality and reactivity of MBH-type reactions is made possible by anion catalysis and a 1,3-Brook rearrangement. In this new reaction, both aliphatic and aromatic aldehydes are rapidly added to silylallenes, leading to gamma-carbinol allenoates at low temperatures. The utility of these reaction products is demonstrated by a fast-tracked synthesis of a [3.2.1] bisoxa bicycle that makes up the framework of many biologically active natural products, including vitisinol D, an antithrombotic agent.

Stereoretentive Halogenations and Azidations with Titanium(IV) Enabled by Chelating Leaving Groups

DedicatedtoProfessorLuigiMandoliniontheoccasionofhis65thbirthdayStereospecific functional group conversions of nonracemicalcohols and diols and their derivatives are of increasingimportance given the powerful catalytic asymmetric reactionsavailable for their synthesis. If neighboring-group participa-tion

SELECTIVE DIHYDROXYLATION OF NON-CONJUGATED DIENES IN FAVOR OF THE TERMINAL OLEFIN

Abstract Non-conjugated dienes were dihydroxylated using the commercially available osmium tetroxide AD-mix-α reagent resulting in highly regioselective dihydroxylation of the terminal olefin rather than the internal, more substituted olefin. These findings now allow for the use of allylmetal reagents on substrates where preexisting internal olefins are present. The resultant diol can be cleaved to the aldehyde allowing for subsequent transformations. This selectivity is controled by a steric effect imposed by the allylic silyl ether adjacent to the internal olefin.

Manganese η2-complexes as auxiliaries for stereoselective aldol synthesis of allenyl carbinols.

A convenient and robust manganese auxiliary was linked via an η(2)-bond to alkynyl esters and ketones using a mild complexation reaction with methylcyclopentadienyl manganese tricarbonyl. This complex readily underwent aldol reactions with exclusive α-substitution and in good diastereoselectivities especially with aryl ketone substrates. This selectivity has been rationalized using a cyclic transition state model in which the manganese auxiliary plays a critical role in promoting E(O)-geometry of the cumulenolate intermediate.

Synthesis of cyclopentadienylmanganese tricarbonyl resins as potential olefin traceless supports

Abstract Cyclopentadienylmanganese tricarbonyl (cymantrene) was attached to polymer support via amide linkages. Two synthetic routes to obtain these cymantrene resins in high yield are reported. Spectroscopic evidence indicates that olefin substrates were loaded to give the corresponding η 2 -complexes under light-promoted ligand exchange conditions by using a THF suspension of these manganese-containing resins. Subsequent treatment of the resin/olefin complex with mild oxidizing agents afforded the starting olefins in high purities.

Organo-Manganese η2-Auxiliary Directed Reactions: A Diastereoselective Approach to 2,3-Allenols

Propargyl aldehydes underwent isomerization to allenyl aldehydes under mildly basic conditions when complexed to an organo-manganese auxiliary using methylcyclopentadienyl manganese tricarbonyl (MMT). This traceless auxiliary magnifies the axial chirality of the allene moiety, allowing for highly diastereoselective additions to the aldehyde carbonyl and subsequent access to an array of 2,3-allenols. Using this strategy, a nitrile-substituted 2,3-allenol was prepared and efficiently converted to Hagens gland lactone.