Regiocontrolled synthesis of cis-enediynes via intramolecular trapping of allylic cations

Trapping of allylic cations possessing 1,2-dialkynyl groups by an external nucleophile such as ROH yields cis-enediynes in a regioselective manner; while similar allylic cations react with an internal nucleophilic group to afford exclusively cis-enediynes. This regiocontrolled allylic rearrangement has been used successfully in the synthesis of a number of 2,5-dihydro-2-benzofuryl cis-enediynes5 and the sulfur analogs.     

Stereoselective synthesis of cyclic ethers via bromine assistedepoxide ring expansion

9-Oxabicyclo[6.1.O]non-4-ene reacts with bromine to give stereoselectively trans, trans-2,6-dibromo-9-oxabicyclo[3.3.1]nonane and trans, trans-2,5-dibromo-9-oxabicyclo[4.2.1]nonane.     

Fluorinative ring-expansion of cyclic ethers using p-iodotoluene difluoride. Stereoselective synthesis of fluoro cyclic ethers

Fluorinated five- to seven-membered cyclic ethers were stereoselectively synthesized from four- to six-membered cyclic ethers having an iodoalkyl substituent by fluorinative ring-expansion reaction using p-iodotoluene difluoride.     

Lactols in stereoselection 2. Stereoselective synthesis of disubstituted cyclic ethers.

Direct reaction of lactols with organometals (Met. = Al, Ti, Zn, Sn) in the presence of Lewis acid provides disubstituted tetrahydrofurans and tetrahydropyrans with high diastereoselectivity.     

Stereoselective intramolecular nitrone cycloadditions to chiral allyl ethers

The Intramolecular nitrone cycloadditions to Z and E chiral allyl ethers afford annulated isoxazolidines with good to excellent stereocontrol in favour of the C-5/C-5' anti isomers. The relative stereochemistry at the stereocenters in C-3/C-4 depends on the length of the chain connecting dipole and dipolarophile.     

Formation of functionalized cyclic ethers by intramolecular nitrile oxide cycloadditions

The reaction of O-trimethylsilyl α-bromo aldoximes with unsaturated alcohols produces oximino ethers which can be readily oxidized with sodium hypochlorite. The transient nitrile oxide intermediate formed undergoes spontaneous cyclization affording fused isoxazolines. MM2 calculations help rationalize the observed stereoselectivity.     

Stereoselective synthesis of 5-7 membered cyclic ethers by deiodonative ring-enlargement using hypervalent iodine reagents

Stereoselective synthesis of 5-7 membered cyclic ethers was achieved by deiodonative ring-enlargement of cyclic ethers having an iodoalkyl substituent. The reaction took place readily under mild conditions using hypervalent iodine compounds and an acetoxy or a trifluoroacetoxy group was introduced into the rings depending on the hypervalent iodine reagent employed. The use of hexafluoroisopropanol (HFIP) as solvent is critical.     

A stereoselective intramolecular halo-etherification of chiral enamides in the synthesis of halogenated cyclic ethers

A stereoselective halo-etherification of chiral enamides is described here. This work provides an approach to halogen containing cyclic ethers and reveals further mechanistic insights to the chemistry of chiral enamides.     

Stereoselective synthesis of eight-membered cyclic ethers by tandem Nicholas reaction/ring-closing metathesis: a short synthesis of (+)-cis-Lauthisan

[STRUCTURE: SEE TEXT] Cis-2,8-disubstituted oxocanes and the parent unsaturated precursors were prepared from the corresponding Co2(CO)6-cycloalkynic ethers. Key steps in such synthesis were the ether linkage formation by intermolecular Nicholas reaction, RCM of the suitable acyclic dienyl ether and montmorillonite K-10 induced isomerization of the complexed cycloalkyne. A short synthesis of (+)-cis-lauthisan taking advantage of the developed methodology is described.     

Stereoselective gamma-lactam synthesis via palladium-catalysed intramolecular allylation

A novel route to the synthesis of 3-(tolylsulfonyl)-4,5-cis-disubstituted gamma-lactams using a diastereoselective palladium-catalysed intramolecular allylation of amino acid-derived allylic carbonates has been developed.     

Stereoselective synthesis of secondary and tertiary propargylic alcohols induced by a chiral sulfoxide auxiliary

The synthesis of optically active secondary and tertiary propargylic alcohols was accomplished by addition of lithium acetylide to chiral β-sulfinyl enones. Only a stoichiometric amount of the lithium acetylide was required and various substituents were tolerated. This reaction could be applied to substrates consisting of both ketones and aldehydes in high yields and excellent diastereoselectivities.     

Copper-catalyzed enantioselective intramolecular conjugate addition/trapping reactions: synthesis of cyclic compounds with multichiral centers

The Cu-catalyzed enantioselective conjugate addition of dialkylzinc to bis-alpha,beta-unsaturated carbonyl compounds followed by the intramolecular trapping of the zinc enolate in the presence of chiral phosphoramidite ligands was investigated. Cyclic and heterocyclic compounds with multichiral centers were formed as a mixture of two diastereomers with excellent diastereoselectivities (up to 99:1) and enantioselectivities (up to 94 % ee, ee=enantiomeric excess). The stereochemistry was determined to be trans,trans for the major products and trans,cis for the minor products. The absolute configuration of the cyclic compounds was assigned by comparison with the analogous adduct derived from trans-3-nonen-2-one and Et(2)Zn or the adduct obtained through conjugate addition of Me(2)Zn to trans-1-phenyl-non-2-en-1-one. Further transformation of these cyclic products into more complex compounds is under investigation in our laboratory.     

Stereoselective synthesis of functionalized vinyl ethers from allyl bromides activated by triethylamine

An efficient coupling reaction of allyl bromides with various alcohols as nucleophiles activated by triethylamine, leading to functionalized vinyl ethers in good yields and with full stereoselectivity.     

Stereoselective synthesis of C-ketosides by sequential intramolecular hydrogen atom transfer-intermolecular allylation reaction

A tandem 1,5 or 1,6 hydrogen atom transfer (HAT)-radical allylation using carbohydrate models is described. The HAT reaction generated a C-glycos-1-yl radical intermediate, which added to allyltri-n-butyltin with high diastereoselectivity, to give C-ketosides with the quaternary carbon carrying two differently functionalized tethers.     

A Stereoselective synthesis of vinyl ethers from α-alkoxyaldehydes

A general, stereoselective approach to vinyl ethers from α-alkoxyaldehydes is described which features a stereocontrolled tri- n-butylstannyl addition/elimination sequence.     

Dilithiated synthons: synthesis of cyclic ethers

Recent advances in the generation of dilithiated synthons by arene-catalyzed lithiation of the corresponding dichloro compounds in the presence of carbonyl compounds (Barbier-type reaction conditions) as the key step are described. Further cyclization of the generated diols under different reaction conditions affords a variety of mono-, bi-, and spirocyclic ethers.     

Platinum-catalyzed intramolecular hydroalkoxylation of gamma- and delta-hydroxy olefins to form cyclic ethers

Reaction of 2,2-diphenyl-4-penten-1-ol with a catalytic mixture of [PtCl2(H2C=CH2)]2 (1 mol %) and P(4-C6H4CF3)3 (2 mol %) at 70 degrees C for 24 h led to the isolation of 2-methyl-4,4-diphenyltetrahydrofuran in 78% yield. The platinum-catalyzed hydroalkoxylation of gamma-hydroxy olefins tolerated substitution at the alpha, beta, and gamma-carbon atoms and at the internal and cis and trans terminal olefinic positions. Platinum-catalyzed hydroalkoxylation tolerated a number of functional groups including pivaloate and acetate esters, amides, silyl and benzyl ethers, and pendant hydroxyl and olefinic groups. Pt-catalyzed olefin hydroalkylation was also applicable to the formation of fused- and spirobicyclic ethers and was effective for the hydroalkoxylation of delta-hydroxy olefins to form tetrahydropyran derivatives.     

Synthesis of cyclic hydrocarbons via intramolecular coupling of bis-pentadienyl iron tricarbonyl cations

A general synthesis for the preparation of medium sized cycloalkanes having 1,2-butadienyl substituents is described. The reaction sequence involved acylation of butadiene-iron tricarbonyl with a diacid chloride, reduction of the resultant diketone to a diol derivative and conversion with HBF₄ to an acyclic bis-pentadienyl Fe(C0)₃ dicationic complex. Upon treatment with zinc the dication undergoes intramolecular ring closure to afford the bis-Fe(C0)₃ complex of the 1,2-dibutadienyl cycloalkane. Five-, six- and ten-membered cyclolalkene derivatives have been prepared in this manner.     

Carbenium ion trapping using sulfonamides: an acid-catalysed synthesis of pyrrolidines by intramolecular hydroamination

Cyclisations of homoallylic sulfonamides proceed smoothly via carbenium ion generation using trifluoromethanesulfonic (triflic) acid, the ease of cyclisation being directly related to the ion stability to give good to excellent yields of the corresponding pyrrolidines. Both toluene- and nitrophenyl-sulfonyl groups are suitable for all substrates tested whereas the corresponding carbamates are only useful in cases of tertiary and highly stabilised carbenium ions. Polyene-derived sulfonamides can also be cyclised to the corresponding polycyclic systems in remarkably high yields, in reactions reminiscent of related cascades encountered in terpene biosynthesis.