Ring Transformation of α-Amino-β-oxoesters to δ-Butyrolactams

δ-Butyrolactams with an exocyclic ester moiety in the δ-position were accessed by reduction of 1-azido-2-cyclopentanone carboxylates with PBu₃ or Zn−AcOH. The ring transformation proceeded readily under the conditions of this reduction which is an unprecedented process. Primary amines formed by catalytic hydrogenation of α-azido-β-oxoesters with larger ring sizes or with benzannulation do not show this rearrangement under the conditions of the azide reduction. In these cases, the ring transformation to respective lactams was achieved by treatment of the α-amino-β-oxoesters with a stoichiometric amount of lithium diisopropylamide.     

Synthetic Studies towards Pheromones by Cyanide-Catalyzed Ring Transformation of α-Hydroxy-β-oxoesters to δ-Valerolactones

The cyanide-catalyzed ring-transformation of α-hydroxy-β-oxoesters to δ-lactones with exocyclic ester moiety is the key transformation for the preparation of racemic 5-hexadecanolide (15 % over nine steps) and 6-acetoxy-5-hexadecanolide (22 % over eight steps), two insect pheromones. The benzyloxycarbonyl moiety is transformed via the acid chloride to the undecanoyl side chain. After reduction of the ketone to the secondary alcohol, this functional group was either reduced via the chloro compound to furnish the 5-hexadecanolide. On the other hand, stereoselective reduction of the ketone gave secondary alcohol with the wrong relative configuration, which was established by X-ray single-crystal structure. Inversion was achieved by reaction of the methanesulfonate with cesium acetate yielding (R*,S*)-6-acetoxy-5-hexadecanolide with the relative configuration also present in the natural product.     

Synthesis of Benzo[b]azocin-2-ones by Aryl Amination and Ring-Expansion of α-(Iodophenyl)-β-oxoesters

Transformation of β-oxoesters with PhI(OCOCF₃)₂ leads to α-(ortho-iodophenyl)-β-oxoesters. These materials are the starting point for the synthesis of 6-carboxybenzo[b]azocin-2-ones by a sequence of aryl amination and ring transformation. This reaction sequence starts with copper-catalyzed formation of N-alkyl anilines from the iodoarenes and primary amines in the presence of K₃PO₄ as stoichiometric base. The intermediate products underwent ring transformation by addition of the nitrogen into the carbonyl group of the cycloalkanone, furnishing benzo-annulated eight-membered ring lactams. Under the same reaction conditions, the cyclohexanone and cycloheptanone derivatives gave no aminated products, but ring-transformed to benzofuran derivatives. The title compounds of this investigation contain two points for further diversification (the lactam nitrogen and the carboxylate function), thus, the suitability of this compound class as a scaffold was proven by appropriate functionalizations. The first series of derivatizations of the scaffold was initiated by hydrogenolytic debenzylation of N-benzyl derivative to provide the NH-congener, which could be deprotonated with LDA and alkylated at nitrogen to give further examples of this compound class. Secondly, the ester function was submitted to saponification and the resulting carboxylic acid could be amidated using HATU as coupling reagent to furnish different amides.     

Synthesis of (ω-Functionalized Alkylheteroatomic Pyrazolyl)-1,2,4-triazoles by Ring Chain Transformation

Treatment of cyclic α-oxo-α-(1,2,4-triazol-1-yl) ketene S, S; N, O-acetals with hydrazine affords title compounds 3a–d and 6a–e by way of a ring chain transformation.     

Enantioselective Hydrogenation of α,β-Unsaturated Cyclic Ketones by Double Asymmetric Induction Preparation of (R)-Muscone

(R)-Muscone[(R)-6]isanodoriferouscomPoundisolatedfromthemalemuskdeer.BecauseofthenatUralsupplyisseverelylbotofanumberofSyntheticmethodshaveaPPearedintheliteratUre['].However,eachofthepublishedenahoselechveopthehcprocessessuffersfromoneormoreofthefollowingflollgandcomplicatedprocess,lowcheforcalandophcalvields,andscarcityofstartingmaterials[2].Inl98o,TrostetaldeveloPedashortprocesstoopthesize(dl)-musconeingoodcheforca1yteld,andthestartinmaterialiseasil3'a.ailablef3];Ouradriistoobtain(R)-mu…     

Synthesis of α-amino-β-keto-esters (β-oxodipeptides)

The synthesis of α-amino-β-keto-esters (β-oxo dipeptides) was studied. Corresponding α-amino-β-ketoesters were prepared from BOC-(L)-Valine and BOC-(L)-isoleucine by coupling with (D,L)-threonine hydrochloride and oxidation with Dess-Martin periodinane (DMP) with a total yield of 48% and 38%, respectively. __________ Translated from Chemistry Online, 2007, 70(10): 793–796 [译自: 化学通报]     

Ring opening of fluoroalkyl-containing α,β-epoxyketones by aromatic amines

Aromatic amines cause ,-epoxyketones containing a -fluoroalkyl group to undergo ring opening at the -position to give -amino--hydroxyketones.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 882–883, May, 1994.     

Synthesis of (Z)-β-(Carbonylamino)alkenylindium through Regioselective anti-Carboindation of Ynamides and Its Transformation to Multisubstituted Enamides

The regioselective anti-carboindation of ynamides by using InBr₃ and silylated nucleophiles was developed to synthesize (Z)-β-(carbonylamino)alkenylindiums. The X-ray crystallographic analysis of an alkenylindium suggested that the reaction proceeded in an anti-addition fashion. In contrast to reported syn-carbometalations of ynamides by using organometallics, a cooperation of InBr₃ and silylated nucleophiles to ynamides achieved an anti-addition, which was supported by DFT calculations. The scope of substrates included various ynamides and silylated nucleophiles, such as silyl ketene acetals and silyl ketene imines. The transformation of synthesized alkenylindiums by iodination, radical coupling, and Pd-catalyzed cross-coupling successfully afforded trisubstituted enamines with high regio- and stereoselectivities.     

Direct α-Functionalization of Saturated Cyclic Amines

Recent advances in synthetic methods for the direct α-functionalization of saturated cyclic amines are described. Methods are categorized according to the in situ formed reactive intermediate (α-amino cation, α-amino anion, and α-amino radical). Transition-metal-catalyzed reactions involving other intermediates have been treated as a separate and fourth class.     

Nucleophilicities of Cyclic α-Diazo Carbonyl Compounds

The one-bond nucleophilic reactivities of seven cyclic α-diazo carbonyl compounds in dichloromethane were determined by analyzing the kinetics of their reactions with benzhydrylium ions (one-bond reference electrophiles) at 20 °C according to the Mayr-Patz equation. Though not calibrated for pericyclic reactions, the identified nucleophilicities also reflect relative reactivities of the α-diazo carbonyl compounds in 1,3-dipolar cycloadditions with dimethyl acetylenedicarboxylate. These (3+2)-cycloadditions primarily gave spirocyclic 3H-pyrazoles, which underwent thermal [1,5]-sigmatropic (van Alphen-Hüttel) rearrangements to furnish 1H-pyrazole-fused tricyclic products.     

Synthesis of Eudesmanolides Possessing Denebutenolide and Endocyclic α,β-Unsaturated Butenolide from α-(-)-Santonin

A new and efficient method of double bond functionalization of eudesmanolide was carried out by rearrangement of epoxide with methoxide. which is important to synthesis of bioactive natural products containing denebutenolid (1) and endocyclic α, β -unsaturated butenolide (2).     

Cyclic bis(β-diketonate)- and bis(β-ketoesterate)-bridged titanium and zirconium alkoxide derivatives

Reaction of Ti(OiPr)(4) with various bis(β-diketones) and bis(β-ketoesters) (LH(2)) results in the formation of dimeric complexes [Ti(OiPr)(2)L](2), where each metal centre is coordinated by two terminal OiPr ligands and two bridging β-diketonate or β-ketoesterate groups (L). Macrocycles containing two M(OiPr)(2) moieties are thus formed. Reaction of Zr(OiPr)(4) with the same bis(β-diketones) and bis(β-ketoesters) results in different compounds, depending on the organic spacer connecting the two functional groups. With shorter spacers, the compounds [ZrL(OiPr)(2)](2)·2iPrOH are obtained, with the same structures as the corresponding titanium complexes. With longer spacers, however, complexes with a higher degree of substitution are formed, such as (ZrL(2))(2) and Zr(2)L(3)(OiPr)(2)·2iPrOH. The molecular weight and structure of all compounds was elucidated by ESI-MS. MS/MS of the corresponding [M+Na](+) precursor ions confirmed the proposed structures based on structure-specific product ions. Solution NMR experiments and DFT calculations additionally supported the proposed structures.     

Synthesis of α-(perfluoroalkyl)-ω-(trialkylsilyl)alkanols

The synthesis of alkanols of the general formula R₃Si(CH₂)_nCH(OH)R_F (n = 1–3) is elaborated and their behavior under GC-MS is studied.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1516-1519, June, 1996.     

Chemoselective Bromodecarboxylation of α-Carboxy- α-cinnamoyl Ketene Cyclic Dithioacetals

α-Oxoketene dithioacetals（ compound 1 ） are versatile synthons for organic synthesis due to their specially structural characteristic, that is, the masked ketene is conjugated with the convertible carbonyl in their molecules. Although there have been numerous reports covering the reactions in which they have been taken as 1,3-electrophiles, the reaction at the α-carbon atom of α-oxoketene dithioacetals has seldom been investigated. Junjappa and co-workers found the α- bromination of compound 2 in the presence of NBS led to α-aroyl-α-bromo ketenedithioacetals. However, the flexibility of the functional groups at the α-carbon atom of compound 2 are still limited.     

Improved Synthesis of Cyclic α-Hydrazino Acids of Five- to Nine-Membered Rings and Optical Resolution of 5,6,7-Membered Ring Hydrazino Acids

Synthesis of cyclic α-hydrazino acids of five- to nine-membered rings has been described. Di-tert-butyl or dibenzyl malonate was used as starting materials instead of diethyl malonate, which was used in our first report. Deprotection of tert-butyl or benzyl ester of the final compounds was much easier than that of ethyl or methyl esters. Overall yield of these acids were 39, 50, 47, 52, and 51%, respectively. These acids were then converted to the diastereomers either via the formation of peptides with L-phenylalanine methyl ester or via the formation of esters (for five- to seven-membered rings) with L-2-phenylalaninol. All diastereomers were separated except the nine-membered ring by flash chromatography. Hydrolysis of diastereomeric esters generated the optically pure five-, six- and seven-membered cyclic α-hydrazino acids. In this process, both the enantiomers have been isolated and the chiral auxiliary L-2-phenylalaninol was recovered. Absolute stereochemistry was determined from x-ray crystallographic analysis.     

Addition of a Silyl Ketene Acetal to α,β-Unsaturated Cyclic Anhydrides

Addition of [1-methoxy-2 methyl-1-propenyl)-oxy] trimethylsilane (MTS) to unsymmetrical α,β-unsaturated cyclic anhydrides (namely, itaconic anhydride and citraconic anhydride) as well as symmetrical anhydrides (namely, maleic anhydride and 2,3-dimethylmaleic anhydride) was investigated. Itaconic anhydride isomerizes to citraconic anhydride in the presence of MTS. In the presence of Lewis acid catalysts (Yb(OTf)₃/CH₂Cl₂), MTS adds to itaconic anhydride at room temperature in a 1,4-fashion. 1,2-Addition is the preferred pathway with both 2,3-dimethyl maleic anhydride and citraconic anhydride.     

Microbial Transformation of Taxoids and Synthesis of Taxoids ith an Oxetane Ring

SincethediscoveryofanhcanceragentPaclitaxel(Taxol@),'studiesonTaxUsSPecieshaVebroughtmorethantwohundrednewtaxoidsintothetaxanediterpenoidfaIYuly.'Recently,Zap-DeacetoxytaxinineJ1andsomeofitsanalogswereisolatedinhighamountsfromTaxusyUnnanensisandotherTaresspecies.2Itseemsthat1anditsanalogscanbeusedasstaltingmaterialsforthechemoenZylnaticSynthesisofpaclitaXelanalogs,aswellasvaluableforthestudyofthebiosynthesisoftaxoidsinToosspecies.MicrobialenZymaticSystemsmayserveasPOwerfultoolstOndnd…     

Synthesis of optically active α-(allenyl)- and α-substituted-α-(allenyl)glycines

The synthesis of various types of optically active α-(allenylsilane-containing)glycines via a chirality-transferring ester-enolate Claisen rearrangement of α-acyloxy-α-alkynylsilanes is described. The conversion of the rearranged products into the optically active silicon-free α-(allenyl)- and α-substituted-α-(allenyl)glycines was achieved by the removal of the Me₂PhSi- or TMS group from the allene terminus.