Stereoselective synthesis of Baylis-Hillman-type adducts via allenolates generated by acyl migration

[reaction: see text] The rearrangement of the carbamoyl group in allenyl carbamate 1 in the presence of n-BuLi in situ generates the allenolate 3, which is subsequently intercepted with aromatic aldehydes furnishing (Z)- or (E)-configured Baylis-Hillman-type adducts 4 or 5. The double bond isomers can be interconverted by a retro aldol-type reaction.     

Transition metal-catalyzed reactions of propargylic carboxylates via an initial 1,2-acyloxy migration

Propargylic carboxylates, as a type of easily available alkyne compounds, have attracted considerable attentions in recent decade. Under the catalysis of transition metal complex (Pd, Ru, Pt, Au, Rh etc), one of chemical transformations of propargylic carboxylate is 1,2-acyloxy migration. The resultant alkenyl metallocarbenoid or metal-containing species may undergo a variety of chemical transformations, leading to formation of carbocyclic and heterocyclic compounds. In this review, representative domino reactions initiated by 1,2-acyloxy migration of propargylic carboxylates are summarized, including pentannuations, cycloadditions and rearrangements. Some mechanistic discussions and synthetic applications are also included.     

Total synthesis of 3',5'-C-branched nucleosides

[reaction: see text] A novel total synthesis of 3',5'-C-branched uridine azido acid has been accomplished using stereoselective aldehyde alkynylation, Ireland-Claisen rearrangement, and iodolactonization as the key reactions. Compared to traditional routes that start from carbohydrates, the present methodology is more efficient, flexible for future optimization, and provides access to both enantiomers of the products. Because the key chemistry does not involve the 3'- and 5'-C substituents, our route is a general approach to 3',5'-C alkyl nucleoside analogues.     

Stereoselective synthesis of highly functionalised P-stereogenic nucleosides via palladium-catalysed P-C cross-coupling reactions

We have shown that the configuration at the P-stereogenic centre in a range of H-phosphonates can be assigned using a combination of chromatographic mobility, ¹H and ³¹P NMR data. We have also shown that the individual P-stereoisomers can be cross-coupled with vinyl and aryl halides, in the presence of a palladium(0) catalyst, to afford the corresponding vinyl- and arylphosphonates in a stereocontrolled manner.     

Efficient synthesis of 2-deoxy L-ribose from L-arabinose: mechanistic information on the 1,2-acyloxy shift in alkyl radicals

[formula: see text] Conversion of the inexpensive L-arabinose 1 into the ethylthio ortho ester 7 followed by generation of the dialkoxyalkyl radical III produces the desired 2-deoxy-L-ribose triester 4 in excellent overall yield. It has been shown that the similar dialkoxyalkyl radical IV is not an intermediate in the 1,2-acyloxy shift of anomeric radical I.     

Stereoselective synthesis of 1,2-diamino-1,2-diarylethane derivatives

A procedure was developed for selective opening of the cis-2,4,5-triarylimidazoline ring to form erythro-1,2-diamino-1,2-diarylethane derivatives. These ring-opening products, erythro-ethylenediamine derivatives, can undergo quantitative isomerization to threo-ethylenediamine derivatives in the presence of strong bases in DMSO.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 1, pp. 206–209, January, 2005.     

Stereoselective preparation of 1-siloxy-1-alkenylcopper species by 1,2-Csp2-to-O silyl migration of acylsilanes

1-Siloxy-1-alkenylcopper species were generated by 1,2-Csp2-to-O silyl migration of the copper enolates of acyltriphenylsilanes. The alkenylcopper species reacted with methyl, benzyl, allylic, and tributylstannyl halides to give geometrically pure (Z)-enol silyl ethers. In the presence of Pd(0) catalyst, the cross-coupling of the alkenyl copper species with aryl and alkenyl iodides also proceeded to give the (Z)-enol silyl ethers with high stereoselectivity.     

Fragmentation of carbohydrate anomeric alkoxyl radicals: new synthesis of chiral 1-fluoro-1-halo-1-iodoalditols

A new general methodology for the synthesis of 1,1,1-trihaloalditols by starting from 1,5-anhydro-2-deoxy-hex-1-enitol derivatives (glycals) is described. The halogens are introduced sequentially in each of the three different steps of the process. The fluorine is introduced in the first step by electrophilic fluorination of the starting glycal; next, hydroxyhalogenation of the resulting vinyl fluoride allows the addition of any halogen (F, Cl, Br or I) at will, and finally, an iodine atom is inserted through an alkoxyl radical fragmentation reaction. This methodology allows the preparation of diverse types of 1,1,1-trihalogenated compounds (R--CF(2)I, R--CFI(2), R--CFClI and R--CFBrI) under mild conditions compatible with sensitive substituents. In some cases, the diastereomeric mixtures generated from R--CFClI and R--CFBrI can be chromatographically separated, and their configuration determined by X-ray crystallographic analysis. The synthetic usefulness of these compounds has been preliminarily assessed by examining the reactivity of the fluorinated radical generated by rupture of the C--I bond.     

Stereoselective synthesis of d- and L-carbocyclic nucleosides by enzymatically catalyzed kinetic resolution

An efficient synthesis of (S)- or (R)-3-(benzyloxy-methyl)-cyclopent-3-enol was developed by appling an enzyme-catalyzed kinetic-resolution approach. This procedure allowed the syntheses of the enantiomeric building blocks (S)- and (R)-cyclopentenol with high optical purity (>98?% ee). In contrast to previous approaches, the key advantage of this procedure is that the resolution is done on the level of enantiomers that only contain one stereogenic center. Owing to this feature, it was possible to chemically convert the enantiomers into each other. By using this route, the starting materials for the syntheses of carbocyclic D- and L-nucleoside analogues were readily accessible. 3',4'-Unsaturated D- or L-carbocyclic nucleosides were obtained from the condensation of various nucleobases with (S)- or (R)-cyclopentenol. Functionalization of the double bond in 3'-deoxy-3',4'-didehydro-carba-D-thymidine led to a variety of new nucleoside analogues. By using the cycloSal approach, their corresponding phosphorylated metabolites were readily accessable. Moreover, a new synthetic route to carbocyclic 2'-deoxy-nucleosides was developed, thereby leading to D- and L-carba-dT. D-Carba-dT was tested for antiviral activity against multidrug-resistance HIV-1 strain E2-2 and compared to the known antiviral agent d4T, as well as L-carba-dT. Whilst L-carba-dT was found to be inactive, its D-analogue showed remarkably high activity against the resistant virus and significantly better than that of d4T. However, against the wild-type virus strain NL4/3, d4T was found to be more-active than D-carba-dT.     

Fragmentation of carbohydrate anomeric alkoxy radicals: a new synthesis of chiral 1-halo-1-bromo compounds

The reaction of 1,2-halohydrins derived from easily available carbohydrates with (diacetoxyiodo)benzene (DIB) in the presence of bromine is a mild procedure for the synthesis of 1-deoxy-1-halo-1-bromo-alditols with one carbon less than the original carbohydrate. The reaction goes through β-fragmentation of the intermediate anomeric alkoxyl radicals. These 1-halo-1-bromo polyhydroxy compounds may be valuable synthetic intermediates in organic synthesis.     

Fragmentation of carbohydrate anomeric alkoxy radicals: a new synthesis of chiral 1-halo-1-iodo alditols

Treatment of 1,2-fluorohydrins, 1,2-chlorohydrins, 1,2-bromohydrins, and 1,2-iodohydrins of the D-gluco, D-galacto, D-lacto, L-rhamno, D-allo, L-arabino, 3-deoxy-D-gluco, and 3,4-dideoxy-D-gluco families of carbohydrates with the (diacetoxyiodo)benzene/iodine system afforded 1-fluoro-1-iodo, 1-chloro-1-iodo, 1-bromo-1-iodo, and 1,1-diiodo alditols, respectively, in excellent yields. The reaction was achieved by radical fragmentation of the C1bond;C2 bond, triggered by the initially formed anomeric alkoxy radical, and subsequent trapping of the C2-radical by iodine atoms. This methodology is compatible with the stability of the protective groups most frequently used in carbohydrate chemistry. The potential utility of these 1-halo-1-iodo alditols as chiral synthons was evaluated by their transformation into alk-1-enyl iodides and in the Takai E-olefination reaction.     

Fragmentation of carbohydrate anomeric alkoxyl radicals: a new synthesis of 1,1-difluoro-1-iodo alditols

[reaction: see text]. The beta-fragmentation of 2,2-difluoro-saccharide anomeric alkoxyl radicals, generated under oxidative condition by treatment of the respective alcohols with (diacetoxyiodo)benzene (DIB) and iodine, afforded 1,1-difluoro-1-iodo alditols in high yield. The reactivity of the fluorinated radical generated by rupture of the C-I bond has been preliminarily assessed by reductive deiodination with tributyltin hydride/AIBN and intermolecular allylation using the Keck reaction.     

Stereoselective synthesis of 1,2-aminoalcohols by [2,3]-wittig rearrangements

[2,3]-Wittig rearrangements of (E)-3-aza-allylic alcohol derivatives can provide access to functionalized 1,2-aminoalcohols with high syn or anti diastereoselectivity depending on the anionic stabilizing group (amide or alkyne).     

Factors controlling the equilibrium of Pt-catalyzed [1,2]- versus [1,3]-acyloxy migration

Pick a pathway: Upon activation with an electrophilic transition-metal catalyst, a propargylic acetate undergoes competing [1,2]- and [1,3]-acyloxy migration depending on the reaction temperature as well as the substituent pattern around the alkyne. The nature of the catalyst also affects the reaction course. The reactions provided clear evidence for the interconversion between carbenoid and allene intermediates (see scheme).     

Stereoselective synthesis of substituted 1,3-oxazolidines via Pd-catalyzed carboamination reactions of O-vinyl-1,2-amino alcohols

The stereoselective synthesis of 2,4- and 2,5-disubstituted 1,3-oxazolidines is accomplished via Pd-catalyzed carboamination of O-vinyl-1,2-amino alcohol derivatives. The transformations generate cis-disubstituted products with good to excellent diastereoselectivity, and enantiomerically enriched substrates are converted without loss of optical purity. In addition to yielding synthetically useful products that are difficult to generate with existing methods, these transformations illustrate that electron-rich enol ethers are viable substrates for alkene carboamination processes.     

Stereoselective synthesis of 2-methylenepyrrolizidines by tandem cyclization of N-propargylaminyl radicals

Tandem cyclization of N-propargylaminyl radicals, generated by N-chlorination of (E)-alk-4-enylamines 2a-d and 2f followed by treatment with tributyltin radical, afforded 2-methylenepyrrolizidines 3a-d and 3f in a highly stereoselective manner. A similar radical cyclization of (Z)-N-propargyl-1-methyl-5-phenylpent-4-enylamine (2e) gave pyrrolizidine 3b having the same stereochemistry as that obtained from the E isomer 2b.     

Stereoselective synthesis of optically active alpha-hydroxy ketones and anti-1,2-diols via asymmetric transfer hydrogenation of unsymmetrically substituted 1,2-diketones

[reaction: see text] A well-defined chiral Ru catalyst RuCl(N-(p-toluenesulfonyl)-1, 2-diphenylethylenediamine)(eta(6)-arene) effectively promotes asymmetric transfer hydrogenation of 1-aryl-1,2-propanedione with HCOOH/N(C(2)H(5))(3), leading preferentially to optically active 1-aryl-2-hydroxy-1-propanone with up to 99% ee and 89% yield at 10 degrees C. The reaction at 40 degrees C gives anti-1-aryl-1, 2-propanediol with up to 95% ee and 78% yield. This is a highly efficient procedure for the synthesis of optically active anti-diols.     

Stereoselective synthesis of trifluoromethyl-substituted 1,2-diamines by aza-Michael reaction with trans-3,3,3-trifluoro-1-nitropropene

Aza-Michael addition of optically pure 4-phenyl-2-oxazolidinone to 3,3,3-trifluoro-1-nitropropene proceeds smoothly at low temperature with a high yield. Diastereoselectivity of the addition depends on the base used and lithiated species proved to be highly efficient affording 92% de. Optically pure 1,2-diamino-3,3,3-trifluoropropane is prepared in 58% yield from the aza-Michael addition product through a three-step procedure.     

硫叶立德途径立体控制合成乙烯基型环氧化合物

在相转移条件下(CH3CN/KOH/RT)乙烯基型硫叶立德和醛反应高产率地得到以反式为主的产物,而在低温溴化锂存在下(LiBr/KHMDS/THF/-90℃)得到以顺式为主的产物,对于通过反应条件的变换而改变反应产物立体化学的机理,给出了一个初步的解释。