Low-valent titanium(II) mediated intramolecular and regioselective alkyne/alkoxyallene reductive coupling reactions.

Low-valent titanium(II) complexes turned out to be suitable reagents in the promotion of alkyne/alkoxyallene coupling reactions in an intramolecular fashion. The conditions developed herein led to a broad range of highly functionalized cyclic adducts with excellent regioselectivities toward the central carbon of the alkoxyallene moiety. Good yields (up to 76%) were obtained over 19 examples.

Access to Conjugated Enynes via Allenyl Silver Formation/Cyclization/Decarboxylation Reaction Catalyzed by Silver Carbonate(I).

Herein, we develop a novel and straightforward access to cyclic conjugated enynes catalyzed by silver carbonate/DBU from readily available substrates with good yields. The reaction is easy to set up, broad in scope, and can also be conducted in a one-pot fashion from easily accessible substrates through a sequence Michael addition reaction/cyclization. Based on our previous works, the mechanism proposed would involve an allenyl silver intermediate and decarboxylation reaction.

Silver oxide(I) promoted Conia-ene/radical cyclization for a straightforward access to furan derivatives.

A novel access to fused furan cores using silver oxide(I) has been developed. Mechanistic investigations indicate the involvement of a Conia-ene reaction/radical cyclization for an expedient path to complex furan derivatives. The reaction is broad in scope with interesting atom economy and can also be conducted in a one-pot fashion from readily accessible α,β-unsaturated ketones.

Gold(I)-Catalyzed 7- Cyclization: A Key Step to Access the Bicyclo[4.2.1]nonane Skeleton of Vibsatin A, a Neurotrophic Diterpenoid.

Vibsatin A is a new neurotrophic vibsane-type diterpenoid comprising a bridged bicyclo[4.2.1]nonane skeleton.

Low-valent dialkoxytitanium(ii): a useful tool for the synthesis of functionalized seven-membered ring compounds.

Herein, we describe unprecedented access to all-carbon or heterocyclic seven-membered ring frameworks from 1,8-ene-ynes promoted by inexpensive low-valent titanium(ii) species, readily available from Ti(OiPr) and Grignard reagent. A broad range of cycloheptane, azepane or oxepane derivatives has been obtained (19 examples) with moderate to good yields and an excellent selectivity (up to 95/5 d.r.

Silver(I) Oxide-/DBU-Promoted Synthesis of Dihydrofuran Units through Allenyl Silver Formation.

A formal [3+2] cyclization mediated by silver(I) oxide and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) is described herein.

Ti(II) and Rh(I) Complexes as Reagents toward a Thapsigargin Core.

A novel approach toward the [5-7]fused bicyclic core of thapsigargin, a subnanomolar inhibitor of the endo/sarcoplasmic calcium ATPase (SERCA), is presented. The synthetic route includes an original Ti(II)-mediated hydroxy-directed reductive coupling of an enantiomerically enriched propargylic alcohol and an intramolecular Rh(I)-catalyzed cyclocarbonylation reaction as key steps. Interestingly, through the first experiments of titanocene-mediated reductive cyclization of a 1,8-enyne, a seven-membered cycle was isolated as a unique product with a total diastereoselectivity.

Assembly of the Entire Carbon Backbone of a Stereoisomer of the Antitumor Marine Natural Product Hemicalide.

A strategy for the assembly of the entire carbon backbone of a stereoisomer of the antitumor marine natural product hemicalide has been investigated. The devised convergent approach relies on Horner-Wadsworth-Emmons and Julia-Kocienski olefination reactions for the construction of the C6=C7 and C34=C35 double bonds, respectively, an aldol reaction to create the C27-C28 bond, and a Suzuki-Miyaura cross-coupling as the endgame to form the C15-C16 bond.

Elaboration of Sterically Hindered δ-Lactones through Ring-Closing Metathesis: Application to the Synthesis of the C1-C27 Fragment of Hemicalide.

The synthesis of the C1-C27 fragment of hemicalide, a marine metabolite displaying a unique potent antiproliferative activity, has been accomplished. The synthetic approach highlights a remarkably efficient ring-closing metathesis reaction catalyzed by Nolan ruthenium indenylidene complexes to elaborate the highly substituted δ-lactone framework.

Alkoxyallene-ynes: Selective Preparation of Bicyclo[5.3.0] Ring Systems Including a δ-Alkoxy Cyclopentadienone.

The development of an intramolecular rhodium(I)-catalyzed Pauson-Khand reaction of alkoxyallene-ynes with a proximal alkoxy group is reported. This reaction, in the presence of a [Rh(cycloocta-1,5-diene)Cl]2/propane-1,3-diylbis(diphenylphosphane) system under a CO atmosphere, constitutes a powerful tool for selectively accessing carbo- and heterobicyclo[5.3.

Synthetic Studies toward the C32-C46 Segment of Hemicalide. Assignment of the Relative Configuration of the C36-C42 Subunit.

The synthesis of five diastereomeric model compounds incorporating the C32-C46 segment of the antitumor marine natural product hemicalide has been achieved through a convergent approach relying on the 1,4-addition of an alkenyl boronate to an α,β-unsaturated δ-lactone followed by α-hydroxylation of an enolate and a Julia-Kocienski olefination. Comparison of the (1)H and (13)C NMR data of the model compounds with those of hemicalide enabled the assignment of the relative configuration of the C36-C42 subunit.

Synthetic studies on hemicalide: development of a convergent approach toward the C1-C25 fragment.

Synthetic studies on hemicalide, a recently isolated marine natural product displaying highly potent antiproliferative activity and a unique mode of action, have highlighted a reliable Horner-Wadsworth-Emmons olefination to create the C6-C7 alkene and a remarkable efficient Suzuki-Miyaura coupling to form the C15-C16 bond, resulting in the development of a convergent approach toward the C1-C25 fragment.

Relative stereochemical determination and synthesis of the C17-C25 δ-lactone fragment of hemicalide.

Hemicalide is a novel marine metabolite polyketide distinguished by a unique mechanism of action. Because of insufficient quantities of purified material, this natural product has evaded complete stereochemical assignments. Recently, we have determined the relative stereochemistry of the C8-C13 hexad by synthesizing the C1-C13 fragment.

Asymmetric synthesis of a highly functionalized enantioenriched system close to thapsigargin framework.

A straightforward approach to a highly functionalized enantioenriched bicyclo[5.3.0]decadienone system close to the thapsigargin framework has been achieved.

Conception, synthesis, and biological evaluation of original discodermolide analogues.

Due to its intriguing biological activity profile and potential chemotherapeutic application discodermolide (DDM) proved to be an attractive target. Therefore, notable efforts have been carried out directed toward its total synthesis and toward the production and evaluation of synthetic analogues. Recently, we achieved the total synthesis of DDM.

Relative stereochemical determination and synthesis of the C1-C17 fragment of a new natural polyketide.

The challenging determination of the relative stereochemistry of a complex natural polyketide portion was achieved. After careful NMR analysis, a concise synthesis of a set of possible relative diastereomers (only 6 diastereomers out of the 32 initially envisioned) has been carried out using a common strategy based on enantioselective aldol reactions. With a high predictability, final NMR comparison established the relative stereochemistry of the C1-C17 fragment of this natural product.

Total synthesis of discodermolide: optimization of the effective synthetic route.

An efficient and modulable total synthesis of discodermolide (DDM), a unique marine anticancer polyketide is described including related alternative synthetic approaches. Particularly notable is the repeated application of a crotyltitanation reaction to yield homoallylic (Z)-O-ene-carbamate alcohols with excellent selectivity. Advantage was taken of this reaction not only for the stereocontrolled building of the syn-anti methyl-hydroxy-methyl triads of DDM, but also for the direct construction of the terminal (Z)-diene.

Ligand-activated lithium-mediated zincation of N-phenylpyrrole.

Metalation of N-phenylpyrrole by using an in situ mixture of ZnCl(2)TMEDA (0.5 equiv; TMEDA=N,N,N',N'-tetramethylethylenediamine) and LiTMP (1.5 equiv; TMP=2,2,6,6-tetramethylpiperidino) was optimized.

Asymmetric total synthesis of the 1-epi-aglycon of the cripowellins A and B.

[structure: see text] The unusual [5.3.2]-bicyclic structure of the insecticidal Amaryllidaceae alkaloids cripowellin A (1) and B (2) has been synthesized for the first time via a sequence of Sharpless dihydroxylation, ring-closing metathesis, and intramolecular Heck reaction.