Fluorinated analogues of tert-butyl alcohol as novel protecting groups for use in fluorous synthesis.

[reaction--see text] A series of fluorous derivatives of tert-butyl alcohol were prepared and evaluated as reagents for the protection of carboxylic acids for use in fluorous synthesis. Alcohol 3b can be employed efficiently to protect and immobilize medium-size nonpolar carboxylic acids in a fluorous phase.

Synthesis of N-(3-arylpropyl)amino acid derivatives by Sonogashira types of reaction in aqueous media.

[reaction: see text]. N-propargylamino acids and peptides including them can be efficiently derivatized in aqueous media with a wide variety of (hetero)aryl halides by cross-coupling reactions catalyzed by palladium on carbon (10% Pd/C).

Access to [6.4.0]carbocyclic systems by tandem metathesis of dienynes. A step toward the synthesis of a PreD3-D3 transition state analogue.

[reaction: see text] A new approach to the synthesis of linearly fused 6-8-6 tricarbocyclic systems, tandem ring-closing metathesis of dienynes, allows access to compounds with a carbon framework analogous to the proposed transition state of the isomerization of previtamin D(3) to vitamin D(3).

Construction of bridged polycyclic systems via radical cyclizations. Uncovering of a novel carbocyclization-ring expansion sequence.

[reaction: see text]. While exploring the application of radical cyclizations to the construction of bridged polycyclic systems, we have discovered a novel tandem process consisting of an endo-cyclization of a vinyl radical onto a terminal alkene followed by a one-carbon ring expansion promoted by the resulting secondary radical.

Photochemistry of tosylstilbenoids in the preparation of complex heterocyclic compounds. Synthesis of a cyclopropafuroindolone analogue of the dna-alkylating section of the antitumor compound CC-1065.

[reaction in text] A novel photocyclization of tosylstilbenoids is used in the preparation of a cyclopropafuroindolone analogue of the DNA-alkylating unit of the antitumor compound CC-1065.

Reversal of stereoselectivity in [5 + 2] pyrone--alkene cycloadditons using a sulfoxide-to-sulfoximine switch. Enantiodivergent synthesis of 8-oxabicyclo[3.2.1]octane systems.

[reaction: see text] Switching from a sulfinyl to a sulfonimidoyl group allows the reversal of the sense of asymmetric induction in thermal [5C + 2C] intramolecular pyrone-alkene cycloadditions. Removal of the sulfoximine unit from the resulting cycloadducts yields optically active oxabicyclic systems that are enantiomeric to those obtained using the sulfinyl chiral auxiliary.

Regiocontrolled one-step synthesis of 3,3'-disubstituted 2,2'-bipyridine ligands by cobalt(I)-catalyzed cyclotrimerization.

A one-step, regioselective synthesis of annelated symmetric and asymmetric 3,3'-disubstituted 2,2'-bipyridines by cobalt(I)-catalyzed [2+2+2] cycloadditions between 5-hexynenitrile and 1,3-diynes is described. In the symmetric case, the total regioselectivity of the first cycloaddition is ensured electronically by the conjugation of the triple bonds, and for aminomethylated diynes that of the second is ensured by the cobalt coordinating to the aminomethyl rather than to the hexynenitrile nitrogen. In the asymmetric case, the first cycloaddition took place chemoselectively, which in the case of bis(trimethylsilyl)-1,3,5-hexatriyne (viewed as a 1,3-diyne) is explained by semiempirical calculation of LUMO coefficients. The copper(I) complex of 6b, constituting the first reported complex of the form ML2 (L is a symmetric 3,3'-disubstituted 2,2'-bipyridine), has been prepared. It had UV/Vis and NMR spectra reflecting the 3-substituent-induced mutual torsion of the bipyridine rings in the cis conformation, as was confirmed by x-ray diffractometric determination. The bipyridine 6c forms the dinuclear complex [Cu2(6c)2(CH3CN)2]2+ in the solid state.

Selective palladium-catalyzed cocyclotrimerization of arynes with dimethyl acetylenedicarboxylate: A versatile method for the synthesis of polycyclic aromatic hydrocarbons

Benzyne (1a) and the substituted derivatives 4,5-difluorobenzyne (1b) and 3-methoxybenzyne (2) undergo chemoselective palladium-catalyzed [2 + 2 + 2]-cocyclotrimerization with dimethyl acetylenedicarboxylate (DMAD) to afford the corresponding phenanthrenes and/or naphthalenes. The major products are phenanthrenes if Pd(PPh(3))(4) is used as the catalyst, naphthalenes if Pd(2)(dba)(3) is used. When the method is applied to polycyclic arynes 3-6, which are generated from the corresponding o-trimethylsilylaryl triflates, the same reactivity pattern is observed: the reaction can be selectively directed either toward the cocyclization of one molecule of aryne and two molecules of alkyne or to the reaction of two molecules of aryne with one molecule of alkyne, by appropriate choice of the palladium catalyst. The synthesis of polycyclic aromatic compounds 33-39 using this methodology is reported.

An expeditious route to eight- and nine-membered carbocycles based on a RCM-ring fragmentation strategy

The presence of a temporary one-atom internal tether in 1,9-deca- and 1,10-undecadienes allows their efficient ring-closing metathesis (RCM). Cleavage of the bridging tether of the resulting bicycles provides eight- or nine-membered carbocycles, medium-sized rings that are difficult to assemble using other currently available procedures.

Intramolecular

2-Propynyldiarylacetylenes undergo thermal intramolecular [4 + 2] cycloaddition to give benzo[b]fluorene derivatives in good yields. The hybridization of the tether connecting the reacting alkynes has a pronounced effect on the course of the reaction. Theoretical calculations and isotopic labeling studies support a mechanism which involves the generation of a cyclic allene intermediate that evolves to the final benzo[b]fluorene.

Kinetic control in the palladium-catalyzed synthesis of C(2)-symmetric hexabenzotriphenylene. A conformational study

The hitherto unisolated, thermodynamically unstable C(2)-symmetric conformer of hexabenzotriphenylene (1) has been efficiently synthesized by palladium-catalyzed cyclotrimerization of 9, 10-didehydrophenanthrene (4). The barriers to conformational interconversion of 1 are examined experimentally and by computational studies.

Unmasking the 6,7,5-tricarbocyclic frame of

Opening of the bridging ether of 8-oxabicyclo[3.2.1]oct-6-ene systems 1,7-fused to a five-membered carbocycle that bears a double bond conjugated to that of the oxabicycle can be induced at low temperaure by the addition of an organolithium reagent. If this double bond is unsubstituted, the opening occurs via an anti-1,6-addition pathway, and if substituted it takes place by means of a more classical syn SN2' addition.

Sulfinyl-directed diastereoselective

Introduction of a homochiral p-tolylsulfinyl group at an appropriate position in the alkene accelerates the thermal [5C + 2C] intramolecular cycloaddition to beta-silyloxy-gamma-pyrones and, most importantly, leads to excellent levels of diastereodifferentiation. The resulting adducts can be easily desulfinylated to give optically active 8-oxabicyclic[3.2.1]octane intermediates which by virtue of their rich functionalization might be susceptible to elaboration into enantiomerically pure natural products containing seven-membered carbocycles and tetrahydrofurans.

A paclitaxel analogue with a 2(3-->20)abeotaxane skeleton: synthesis and biological evaluation.

A paclitaxel analogue having an unusual tricyclic [9.3.1.1] hexadecane skeleton was synthesized from deaminoacyltaxine A, a 2(3-->20) abeotaxane isolated in considerable amounts from the leaves of Taxus baccata L. In preliminary studies, this compound showed a much lower cytotoxicity than paclitaxel.

Teixidol, an abeo-taxane from European yew, Taxus baccata.

A new taxoid, teixidol, was isolated from the leaves of Taxus baccata. Its structure, which features an 11(15-->1)abeo-taxane skeleton consisting of a 5/7/6 membered ring system, was established by spectroscopic analysis.

Inhibition of calcium entry induced by cularines and isocrasifoline in uterine smooth muscle.

The effects of nifedipine, papaverine and four benzylisoquinoline alkaloids (cularine, cularidine, celtisine and isocrasifoline) were studied in isolated rat uterus in order to clarify the mechanism of their relaxant action. All the compounds tested completely relaxed KCl-induced contractions and totally or partially inhibited oxytocin-induced rhythmic contractions. Only papaverine acted intracellularly, promoting relaxation of contractile responses induced by oxytocin or vanadate in a Ca(2+)-free medium. In spite of the structural relationship between papaverine and the other alkaloids, the mechanism of their relaxant action is not the same. The activities of cularine derivatives and of isocrasifoline were similar to that of nifedipine.