Oxygenation vs iodonio substitution during the reactions of alkenyl-silanes with iodosylbenzene: participation of the internal oxy group

Reaction of 4-acyl-oxy-but-1-enyl-silanes with iodosylbenzene in the presence of BF(3) x OEt(2) gave 4-acyloxy-2-oxobutyl-silane and 3-acyloxy-tetrahydrofuran-2-yl-silane via a 1,3-di-oxan-2-yl cation intermediate, which is generated by participation of the acyloxy group during the electrophilic addition of iodine(III) to the substrate.     

Characterization of iodonium salts differing in the anion

The properties and reactivity of a series of iodonium salts with different anions were compared. The nucleophilicity of the anions in such compounds can be characterized by their melting points and NMR spectra. When using Quinaldine Red as indicator and CH3CN as solvent, the acid release rate of the iodonium salts correlated very well with their polymerization results in acid-sensitive epoxides.     

Elimination-addition mechanism for nucleophilic substitution reaction of cyclohexenyl iodonium salts and regioselectivity of nucleophilic addition to the cyclohexyne intermediate

The reaction of 4-substituted cyclohex-1-enyl(phenyl)iodonium tetrafluoroborate with tetrabutylammonium acetate gives both the ipso and cine acetate-substitution products in aprotic solvents. The isomeric 5-substituted iodonium salt also gives the same mixture of the isomeric acetate products. The reaction is best explained by an elimination-addition mechanism with 4-substituted cyclohexyne as a common intermediate. The cyclohexyne formation was confirmed by deuterium labeling and trapping to lead to [4 + 2] cycloadducts and a platinum-cyclohexyne complex. Cyclohexyne can also be generated in the presence of some other mild bases such as fluoride ion, alkoxides, and amines, though amines are less effective bases for the elimination. Kinetic deuterium isotope effects show that the anionic bases induce the E2 elimination (k(H)/k(D) > 2), while the amines allow formation of a cyclohexenyl cation in chloroform to lead to E1 as well as S(N)1 reactions (k(H)/k(D) approximately 1). Bases are much less effective in methanol, and methoxide was the only base to efficiently afford the cyclohexyne intermediate. Nucleophiles react with the cyclohexyne to give regioisomeric products in the ratio dependent on the ring substituent. The observed regioselectivity of nucleophilic addition to substituted cyclohexynes is rationalized from calculated LUMO populations, which are governed by the bond angles at the acetylenic carbons: The less deformed carbon has a higher LUMO population and is preferentially attacked by the nucleophile.     

Synthesis of enamides related to the salicylate antitumor macrolides using copper-mediated vinylic substitution

[formula: see text] A new approach to the assembly of enamides is described using copper(I) carboxylate-catalyzed substitution of vinyl iodides and amides. Modified reaction conditions have been developed to synthesize the O-methyloxime enamide side chains related to the natural products lobatamides A-F, oximidine I and II, and CJ-12,950.     

Michael addition-elimination mechanism for nucleophilic substitution reaction of cycloalkenyl iodonium salts and selectivity of 1,2-hydrogen shift in cycloalkylidene intermediate

Reactions of cyclohexenyl and cyclopentenyl iodonium salts with cyanide ion in chloroform give cyanide substitution products of allylic and vinylic forms. Deuterium-labeling experiments show that the allylic product is formed via the Michael addition of cyanide to the vinylic iodonium salt, followed by elimination of the iodonio group and 1,2-hydrogen shift in the 2-cyanocycloalkylidene intermediate. The hydrogen shift preferentially occurs from the methylene rather than the methine beta-position of the carbene, and the selectivity is rationalized by the DFT calculations. The Michael reaction was also observed in the reaction of cyclopentenyliodonium salt with acetate ion in chloroform. The vinylic substitution products are ascribed to the ligand-coupling (via lambda3-iodane) and elimination-addition (via cyclohexyne) pathways.     

Rare example of nucleophilic substitution at vinylic carbon with inversion: mechanism of methyleneaziridine formation by sodium amide induced ring closure revisited

Intramolecular nucleophilic substitution of the C-Br bond of (E)- and (Z)-2-bromobut-2-enylamines by the pendant nitrogen atom leads to 2-ethyleneaziridines by way of stereochemical inversion at the vinylic carbon atom. The stereochemistry of the products is unambiguously established by X-ray crystallography performed on two derivatives. These cyclizations represent some of the first examples of substitution with inversion in unactivated vinylic substrates. In conjunction with additional deuterium-labeling experiments, the accepted mechanism for this reaction is shown to be flawed.     

Use of acetate as a leaving group in palladium-catalyzed nucleophilic substitution of benzylic esters

The palladium complex prepared in situ from [Pd(η³-C₃H₅)(cod)]BF₄ and bidentate phosphine DPPF was a good catalyst for the nucleophilic substitution of benzyl acetate. Significant acceleration of the palladium-catalyzed substitution was observed when an alcohol was employed as a reaction solvent. The palladium catalyst was effective for the benzylation of various stabilized carbanions, amines, and benzenesulfinate with benzylic acetates.     

Neighbouring group participation in phosphate esters. Fragmentation of {2-arylethyl} phosphorochloridates

(β-Arylethyl)phosphorochloridates decompose easily yielding 1-chloro-2-arylethanes and/or arylethylenes, presumably via the concerted P-Cl fission and the expulsion of metaphosphate-like species.     

Pushing radical cyclization from regioselective to regiospecific: cyclization of amidyl radicals controlled by vinylic halogen substitution

Efficient and regiospecific 6-exo, 7-endo, 7-exo, and even 8-endo amidyl radical cyclizations can be accomplished by the direct reactions of unsaturated N-H amides if they bear a vinylic halogen (Cl, Br, I) substituent. This remarkable halogen-substitution effect could be rationalized in terms of lone pair-lone pair electron repulsion between the N radical and the vinylic halogen atom, in addition to the well-known steric and radical-stabilizing effect. [reaction: see text]     

Use of alkyl 2,4,6-triisopropylbenzoates in the asymmetric homologation of challenging boronic esters

(-)-Sparteine induced lithiation of primary 2,4,6-triisopropylbenzoates and subsequent homologation of boronic esters is reported. A comparative study with lithiated N,N-diisopropylcarbamates has demonstrated the superiority of the hindered benzoate.     

A direct route to triazole boronic esters and their application in the synthesis of small molecule arrays

Alkynylboronates represent useful substrates for the direct synthesis of triazole boronic esters by their thermal cycloaddition with azides. A telescoped cycloaddition-cross-coupling protocol is reported and its employment in the synthesis of a small triazole array is disclosed.     

Neighboring group participation in the additions of iodonium and bromonium ions to N-alkoxycarbonyl-2-azabicyclo[2.2.n]alk-5-enes (n = 1,2)

Additions of iodonium-X reagents to N-alkoxycarbonyl-2-azabicyclo[2.2.1]hept-5-enes and the homologous 2-azabicyclo[2.2.2]oct-5-enes have been found to mirror the outcomes of additions of bromonium-X reagents. Only rearranged products were observed for reactions of either of these halonium ion reagents with the azabicylo[2.2.1]hept-5-enes. For the azabicyclo[2.2.2]oct-5-enes, nitrogen participation in addition of IOH or BrOH was dependent on the N-alkoxycarbonyl group. With larger N-Boc, N-Cbz, or N-Troc protecting groups, unrearranged 5-anti-hydroxy-6-syn-I(or Br)-2-azabicyclo[2.2.2]octanes were formed by nucleophilic attack at C(5) on syn-halonium ions. The structure of N-methyl-8-anti-bromo-4-anti-hydroxy-2-azabicyclo[3.2.1]octane has been reassigned by X-ray analysis.     

Stereochemical relationships in the eudesmane (selinane) group of sesquiterpenes

The stereochemical correlations in the eudesmane¹ group of sesquiterpenes are highly ramified. In this article we attempt to summarise the evidence on which the correlations are founded. Most of the classical chemistry of the group of compounds has been reviewed, and some of the more recent developments have been described by Barton and de Mayo.     

Investigation of the scope of a [3+2] cycloaddition approach to isoxazole boronic esters

The [3+2] cycloaddition reaction of nitrile oxides and alkynylboronates provides direct access to a wide variety of isoxazole boronic esters. Specifically, this technique has been employed to generate trisubstituted isoxazole 4-boronates and disubstituted isoxazoles where the boronic ester moiety can be installed at C-4 or C-5 with high levels of regiocontrol. The application of this methodology in the synthesis of non-steroidal antiinflammatory agents is also described.     

Stereochemical studies on the nucleophilic substitution in the reaction of allyl phosphates with organoaluminium reagents

The reaction of cis- or trans-5-isopropenyl-2-methyl-2-cyclohexenyl diethyl phosphate (I) with Me₂AlX (X = OPh, SPh, NHPh) in hexane results in substitution of the -O-PO(OEt)₂ group with X under predominant inversion. The solvent effects on the stereochemistry in these reactions have been disclosed.