Jan Szymoniak

Tandem carbonyl coupling-rearrangements promoted by the niobium(III) reagent. Dual reductive and Lewis acid properties of NbCl3(DME)

Abstract Benzaldehyde (1a) and acetophenone (6) are shown to undergo highly stereoselective reductive couplings by NbCl3(DME). When the reaction is performed at −10°C, the threo diols can be isolated. The intermediate niobiopinacols reveal the ability of subsequent transformations, due to the Lewis acid properties of the reagent used. Starting from 1a stereospecific acetalization leads to threo-2,4,5-triphenyl-1,3-dioxolane (3a), whereas 3,3-diphenyl-2-butanone (7) is obtained from 6 in a pinacol-pinacolone type rearrangement. Alkenes may also be formed in the competing, temperature controlled deoxygenation The stereoselectivity and the easy control of NbCl3 (DME) mediated reactions make it a promising reagent for further synthetic applications.

A Direct Stereoselective Approach to trans-2,3-Disubstituted Piperidines: Application in the Synthesis of 2-Epi-CP-99,994 and (+)-Epilupinine

A simple synthesis of enantiomerically pure piperidine esters is described, offering a straightforward access to the trans-2,3-disubstituted piperidine skeleton which is present in a broad range of biologically active compounds.

Titanium-mediated synthesis of bicyclic cyclopropylamines from unsaturated nitriles

Here we report an easy synthesis of bicyclic primary cyclopropylamines directly from unsaturated nitriles. The described reaction involves Ti(II)-mediated intramolecular coupling of alkene and nitrile moieties.

Pinacol coupling of aliphatic aldehydes promoted by niobium (III) reagent

Abstract NbCl3 (DME) was found to be a useful reagent for the intermolecular pinacol coupling of aliphatic aldehydes. The high anti diastereoselectivity of this reaction (dl / meso ≥ 9 / 1) did not depend on the variation in the aldehyde alkyl chain. With respect to intramolecular pinacolization, the loss of the stereoselectivity observed is consistent with the mechanism involving an insertion of the oxo-group into the metal-carbon bond of the intermediate niobiooxirane.

Diastereoselective access to nonracemic 2-cis-substituted and 2,6-cis-disubstituted piperidines.

Access to nonracemic amino ketones via a hydrozirconation/transmetalation/acylation sequence applied to Boc-protected 1-aminobut-3-enes is presented. This method was applied to the stereoselective synthesis of cyclic imines (or iminiums) which were diastereoselectively converted into 2-cis-substituted and 2,6-cis-disubstituted piperidines. The potential of this approach in the field of alkaloid synthesis was illustrated by the synthesis of (-)-coniine and (-)-indolizidine 209D. Furthermore, access to indolizidines bearing a quaternary center could also be envisioned through this strategy.

Diene-titanium complexes as synthetic intermediates for the construction of three- or five-membered carbocycles.

It has been shown that diene-titanium complexes exhibit substrate-dependent 1,2- or 1,4-dicarbanion reactivity. On this basis, 3-cyclopentenylamines and spiro-vinylcyclopropane lactams were easily prepared by using homoallylic Grignard reagents, Ti(O-i-Pr)4, and nitriles or cyanoesters, respectively.

Studies on the titanium-catalyzed cyclopropanation of nitriles.

The Ti-mediated reaction of Grignard reagents with nitriles was investigated with sub-stoichiometric amounts of titanium isopropoxide. Cyanoesters were converted to spirocyclopropanelactams in good yields using as low as 0.05 eq of Ti(O(i)Pr)4. Under similar conditions, cyanocarbonates led to spirocyclopropane oxazolidinones and/or aminocyclopropylcarbinols. A very short synthesis of the naturally occurring aminocyclopropanecarboxylic acid illustrates the usefulness of this methodology.

The spirocyclopropyl moiety as a methyl surrogate in the structure of L-fucosidase and L-rhamnosidase inhibitors

Nitrogen-in-the-ring analogues of l-fucose and l-rhamnose were prepared, which feature a spirocyclopropyl moiety in place of the methyl group of the natural sugar. The synthetic route involved a titanium-mediated aminocyclopropanation of a glycononitrile as the key step. Four new spirocyclopropyl iminosugar analogues were generated, which displayed some activity towards l-fucosidase and l-rhamnosidase.

Synthesis of bent titanocene metalloligands with the (diphenylphosphino)tetramethylcyclopentadienyl moiety. X-ray structure of [(η5-C5Me4PPh2)2TiCl2]Mo(CO)4

The reactions of lithium(diphenylphosphino)tetramethylcyclopentadienide with CpTiCl 3 and secondly with TiCl 3 followed by CCl 4 oxidation lead to the formation of two titanocene phosphines: (η 5 -C 5 H 5 )[η 5 -C 5 Me 4 P(C 6 H 5 ) 2 ]TiCl 2 ( 2 ) and [η 5 -C 5 Me 4 P(C 6 H 5 ) 2 ] 2 TiCl 2 ( 3 ), respectively. The metalloligand 3 reacts readily with Mo(CO) 4 cod, Mo(CO) 5 THF and Mo(CO) 6 to give in each case [(η 5 -C 5 Me 4 o(CO) 4 ( 6 ) as a sole product. The structure of 6 has been determined by X-ray diffraction. Crystal data: P , a = 11.716(1), b = 11.753(2), c = 16.110(2) A, α = 99.06(1), β = 92.61(1), γ = 104.20(1)°, Z = 2. The molybdenum-titanium distance of 5.194(1) A rules out any metal-metal interaction. The chlorine substitution reactions by CO in 2 and 3 and by thiolate group (pH 3 C-C 6 H 4 -S) in 16 are reported.

Palladium/Lewis Acid Mediated Domino Reaction of Pentafulvene Derived Diazabicyclic Olefins: Efficient Access to Spiropentacyclic Motif with an Indoline and Pyrazolidine Fused to Cyclopentene

A palladium/Lewis acid mediated stepwise and one-pot transformation of pentafulvene derived diazabicyclic olefins is described. The reaction offers a facile strategy for the synthesis of novel spiropentacyclic motifs with indoline and pyrazolidine fused to the cyclopentene core.