Sulfoxide-controlled SN2′ displacements between cuprates and vinyl and alkynyl epoxy sulfoxides

The S_N2′ displacement of readily available vinyl epoxy sulfoxides with organocopper reagents takes place in good yields with high anti selectivity and a good degree of E/Z stereocontrol to produce enantiopure α-hydroxy vinyl sulfoxides. A second allylic displacement on the related mesyloxy vinyl sulfoxides allows for the asymmetric construction of two adjacent chiral centers. In addition, cuprate mediated S_N2′ addition to alkynyl epoxy sulfoxides affords α-hydroxy allenyl sulfoxides in good yields.     

S(N)2' addition/1,2-elimination of dimethylsulfonium methylide with epoxy vinyl sulfones: synthesis of exocyclic cross-conjugated dienyl sulfones

Dimethylsulfonium methylide undergoes S(N)2' addition/1,2-elimination with epoxy vinyl sulfones to generate enantiopure six and seven membered cross-conjugated hydroxy vinyl sulfones. Moderate to excellent yields were obtained for both six and seven membered substrates.     

S(N) 2' Alkylation of Cyclopropanols via Homoenolates

Reining in reactivity: Stereoselective S(N) 2' alkylation of cyclopropanols has been devised under the control of mixed zinc/copper reagents. This method provides convenient access to enantiopure keto homoenolates which react with electrophiles (El(+) ) to form C?C bonds. M=metal.     

Template effects in S(N)2 displacements for the preparation of pseudopeptidic macrocycles

Macrocyclisation reactions of C(2)-symmetric pseudopeptides containing central pyridine-derived spacers are affected by the presence of different anions. The selection of the proper anion gives excellent results for the preparation of the corresponding macrocyclic structures. Kinetic studies show that the presence of those anions enhances both the yield and the rate of the reaction. Computational studies at the B3LYP/6-31G* level have allowed us to rationalise the experimental results. The obtained transition states (TSs) show that the interaction between the anion and the open-chain pseudopeptidic chain has a stabilising effect. The anion stabilises the two TSs involved: the first one, which involves the formation of the initial bond between the two subunits and leads to an open-chain intermediate, and the second one, which precedes the formation of the cyclic structure. The optimum anion (Br(-) when the central spacer is derived from 2,6-bis(aminomethyl)pyridine, is able to act as a template, in that it forces the two ends of the open-chain intermediate to approach each other by forming hydrogen bonds with the two amino acid subunits present in the intermediate. This stabilises the second TS to a greater extent than the first one, and thus, favours macrocyclisation over the competing oligomerisation reactions. The computational calculations also allowed us to predict the outcome of new experiments. Accordingly, the synthesis of the pseudopeptidic macrocycle derived from 2,6-diaminopyridine was not successful under the optimised conditions previously used. Nevertheless, calculations predicted that in this case Cl(-) should be more efficient than Br(-), and this was subsequently experimentally confirmed. Interestingly, the presence of different substituents on the constituent amino acids seems to play a minor role in the overall process.     

Nucleophilic additions to alkylidene bis(sulfoxides): stereoelectronic effects in vinyl sulfoxides

Conjugate additions of nucleophiles (e.g. enolates, amines and malonate anions) to bis(p-tolylsulfinyl)alkenes, alkylidene-1,3-dithiane-1,3-dioxides and alkylidene-1,3-dithiolane-1,3-dioxides have recently been published. Reasons for different selectivities and reaction rates will be discussed by consideration of steric and electronic effects. The preferred mode of attack can be explained by stereoelectronic effects (hyperconjugation) in the primarily carbanion, which is stabilized by n-->S-O-sigma* interaction with an antiperiplanar S=O group. Calculation of the transition states [BP86/aug-TZVP] for the addition of acetone enolate to the dithiane-derived alkylidene bis(sulfoxide) revealed that 6.6-7.3 kJ mol(-1) more energy is needed for an attack leading to a less-stabilized carbanion. Two axial S=O groups in dithiolane-derived alkylidene bis(sulfoxides) lead to a higher reactivity towards nucleophiles.     

S(N)/S(N)' competition: selective access to new 10-fluoro artemisinins

In this paper, we report a simple route to accede to a new family of C-10 fluorinated derivatives of artemisinin 7. We demonstrated that nucleophilic substitution of the allylic bromide 6 with alcohols can occur at carbon 10 (compounds 7) under solvolytic conditions (S(N)'/S(N) ratio, 87:13). Furthermore, using the particular properties of hexafluoroisopropanol (HFIP), we are able to increase the selectivity of the substitution. Primary alcohols are completely selective for allylic substitution. With amines as nucleophiles, selectivity of substitution is dependent on their nucleophilicity, but attack at carbon 16 was always favored. However, the S(N)'/S(N) ratio could be slightly increased by adding HFIP, which is able to modulate their nucleophilicity through hydrogen bonding. In preliminary in vitro assessments, these new compounds, 7, exhibited a satisfying activity against malaria.     

Facile O-deallylation of allyl ethers via S(N)2' reaction with tert-butyllithium

[reaction: see text] Allylic ethers are converted to the corresponding alcohol or phenol in virtually quantitative yield at temperatures below ambient simply by stirring a hydrocarbon solution of the ether with 1 molar equiv of tert-butyllithium. The reaction, which produces 4,4-dimethyl-1-pentene as a coproduct, most likely involves an S(N)2' attack of the organolithium on the allyl ether.     

Preparation of optically pure propargylic and allylic alcohols from 2-(trimethylsilyl)vinyl sulfoxides as a chiral ethynyl anion synthon: computational studies on elimination reaction of 2-(trimethylsilyl)vinyl sulfoxides

The reaction of the alpha-carbanion derived from (trimethylsilyl)vinyl sulfoxides with aldehydes afforded a diastereomeric mixture of the products. Each diastereomer was subjected to specific elimination reactions to give optically pure propargylic, trimethylsilylated propargylic, and allylic alcohols. Acceleration of the sulfenic acid-elimination from the beta-silylvinyl sulfoxide was demonstrated by the ab initio calculation to be ascribed mainly to the beta-effect of the silyl group.     

First asymmetric cycloaddition of carbonyl ylides to vinyl sulfoxides and furan-2(5H)-ones

The Rh2(OAc)4-catalyzed reactions of o-(methoxycarbonyl)-alpha-diazoacetophenone with enantiomerically pure 5-ethoxy-3-p-tolylsulfinylfuran-2(5H)-ones 1a and 1b afford 4,10-epoxybenzo[4,5]cyclohepta[1,2-c]furan-3,9-diones 6a and 6b, in good or moderate yields and in a completely regioselective way. The pi-facial selectivity is complete for 1a, which only yields anti-6a adducts, and very high for 1b. The endo stereoisomers are favored with respect to the exo ones in both reactions. The sulfinyl group significantly increases the reactivity of the dipolarophile as it has been demonstrated by studying the behavior of 5-methoxyfuran-2(5H)-one (3).     

N-(S)-(1’-氯甲基-2’-烷基)-2-乙基-2-(4S-烷基-4,5-二氢噁唑)丁酰胺的合成

由L-氨基酸不对称合成了4种新型手性化合物(6a,6b,7a,7b),其结构经IR,~1H NMR,~(13)C NMR及MS等证实。     

Polydentate N(2)S(2)O and N(2)S(2)O(2) Ligands as Alcoholic Derivatives of (N,N'-Bis(2-mercaptoethyl)-1,5-diazacyclooctane)nickel(II) and (N,N'-Bis(2-mercapto-2-methylpropane)-1,5-diazacyclooctane)nickel(II)

The synthesis, structural characterization, spectroscopic, and electrochemical properties of N(2)S(2)-ligated Ni(II) complexes, (N,N'-bis(2-mercaptoethyl)-1,5-diazacyclooctane)nickel(II), (bme-daco)Ni(II), and (N,N'-bis(2-mercapto-2-methylpropane)1,5-diazacyclooctane)nickel(II), (bme-daco)Ni(II), derivatized at S with alcohol-containing alkyl functionalities, are described. Reaction of (bme-daco)Ni(II) with 2-iodoethanol afforded isomers, (N,N'-bis(5-hydroxy-3-thiapentyl)-1,5-diazacyclooctane-O,N,N',S,S')halonickel(II) iodide (halo = chloro or iodo), 1, and (N,N'-bis(5-hydroxy-3-thiapentyl)-1,5-diazacyclooctane-N,N',S,S')nickel(II) iodide, 2, which differ in the utilization of binding sites in a potentially hexadentate N(2)S(2)O(2) ligand. Blue complex 1 contains nickel in an octahedral environment of N(2)S(2)OX donors; X is best modeled as Cl. It crystallizes in the monoclinic space group P2(1)/n with a = 12.580(6) ?, b = 12.291(6) ?, c = 13.090(7) ?, beta = 97.36(4) degrees, and Z = 4. In contrast, red complex 2 binds only the N(2)S(2) donor set forming a square planar nickel complex, leaving both -CH(2)CH(2)OH arms dangling; the iodide ions serve strictly as counterions. 2 crystallizes in the orthorhombic space group Pca2(1) with a = 15.822(2) ?, b = 13.171(2) ?, c = 10.0390(10) ?, and Z = 4. Reaction of (bme-daco)Ni(II) with 1,3-dibromo-2-propanol affords another octahedral Ni species with a N(2)S(2)OBr donor set, ((5-hydroxy-3,7-dithianonadiyl)-1,5-diazacyclooctane-O,N,N',S,S')bromonickel(II) bromide, 3. Complex 3 crystallizes in the orthorhombic space group Pca2(1) with a = 15.202(5) ?, b = 7.735(2) ?, c = 15.443(4) ?, and Z = 4. Complex 4.2CH(3)CN was synthesized from the reaction of (bme-daco)Ni(II) with 1,3-dibromo-2-propanol. It crystallizes in the monoclinic space group P2/c with a = 20.348(5) ?, b = 6.5120(1) ?, c = 20.548(5) ?, and Z = 4.     

Cross-metathesis reaction of vinyl sulfones and sulfoxides

Cross-metathesis reactions of α,β-unsaturated sulfones and sulfoxides in the presence of molybdenum and ruthenium pre-catalysts were tested. A selective metahesis reaction was achieved between functionalized terminal olefins and vinyl sulfones by using the ‘second generation’ ruthenium catalysts 1c-h while the highly active Schrock catalyst 1b was found to be functional group incompatible with vinyl sulfones. The cross-metathesis products were isolated in good yields with an excellent (E)-selectivity. Both the molybdenum and ruthenium-based complexes were, however, incompatible with α,β- and β,γ-unsaturated sulfoxides.     

From vinyl sulfides, sulfoxides and sulfones to vinyl zirconocene derivatives

An easy and straightforward new method for the preparation of sp² zirconocene derivatives from a wide range of heterosubstituted alkenes such as vinyl sulfides, sulfoxides and sulfones is described. In all cases, a complete isomerization of the stereochemistry is observed and only the E-isomer is obtained. The reactivity of the resulting vinylic organometallic can be increased by a transmetalation reaction into organocopper, organozinc or organopalladium species and, therefore, several carbon-carbon formation were easily realized.