Synthesis of Geminally Activated 4-(Furan-2-yl)- and 4-(Thiophen-2-yl)-1-nitrobuta-1,3-dienes

The condensation of 3-(furan-2-yl)- and 3-(thiophen-2-yl)prop-2-enals with nitro-substituted CH acids, namely ethyl nitroacetate, nitroacetone, nitroacetophenone, and nitroacetonitrile, afforded a series of geminally activated nitro dienes, 4-(furan-2-yl)- and 4-(thiophen-2-yl)-1-nitrobuta-1,3-dienes. The product structure was confirmed by NMR and IR spectroscopy.

     

Studies of Diastereoselectivity in Diels-Alder Reactions of Enantiopure (SS)-2-(p-Tolylsulfinyl)-1,4-naphthoquinone and Chiral Racemic Acyclic Dienes

Enantiopure sulfinylnaphthoquinone (+)-5 reacted with racemic acyclic dienes 1a-f bearing a stereogenic allylic center, through a tandem cycloaddition/pyrolytic sulfoxide elimination, to afford optically enriched compounds 8a-f and 9a-f with good like/unlike selectivities (ca. 75:25) and good enantiomeric excesses (68-82%), arising from the partial kinetic resolution of the racemic dienes. The opposite diastereoselection (8g-i: 9g-i, up to 5:95) was observed in reactions with dienes 1g-i, having an additional methyl group at C-3, the enantiomeric purities being moderate (14-25%). Steric effects and torsional interactions in the corresponding approaches account for the observed diastereoselectivities.     

(2E)-4,4-Dimethoxy-2-butenal in the Synthesis of Conjugated Dienes and Dienals

Using (2E)-4,4-dimethoxy-2-butenal as starting compound, methods were developed for synthesis of (2E,4E)- and (2E,4Z)-dimethoxyalkadienes. Deacetalization of the latter gives with high yield the corresponding dienals which are naturally occurring compounds and also synthons for preparation of conjugated dienes as key compounds for building up other natural products.     

Stereospecific preparation of (Z)- and (E)-2,3-difluoro-3-stannylacrylic ester synthons and a new, efficient stereospecific route to (Z)- and (E)-2,3-difluoroacrylic esters

[reaction: see text] The (Z)-2,3-difluoro-3-stannylacrylic ester is readily prepared from (Z)-1,2-difluorovinyltriethylsilane via stereospecific stannyl/silyl exchange with KF/(Bu3Sn)2O or Bu3SnCl in DMF at 70 degrees C. The corresponding (E)-2,3-difluoro-3-stannylacrylate is prepared by stereospecific carbonylation of (E)-1,2-difluorovinyl iodide followed by low temperature/in situ stannylation of the resultant (Z)-2,3-difluoroacrylic ester. With Cu(I) iodide and Pd(PPh3)4 catalysis, the (Z)- and (E)-stannylacrylate esters readily couple with aryl iodides and vinyl bromides, as well as 2-iodothiophene, at room temperature to stereospecifically produce the respective (E)- and (Z)-2,3-difluoro-3-aryl substituted acrylic esters or conjugated dienes in high yields.     

Synthesis and dienophilic behavior of (S)-2-cyano-3-(p-tolylsulfinyl)-1,4- benzoquinone

Hydrocyanation of 2-(p-tolylsulfinyl)-1,4-benzoquinone (2) followed by oxidation with PhI(OAc)(2) gives 2-cyano-3-(p-tolylsulfinyl)-1,4-benzoquinone (1). The generation of 1 in the presence of cyclic and acyclic dienes affords the Diels-Alder adducts with a complete chemo- (only reaction with the sulfinyl-substituted double bond takes place), regio- (controlled by the cyano group), and endo selectivity (with respect to the quinone moiety), whereas the pi-facial selectivity is dependent on the structure of the diene.     

Economical and environmentally friendly syntheses of 2-(phenylsulfonyl)-1,3-cyclohexadiene and 2-(phenylsulfonyl)-1,3-cycloheptadiene.

A large-scale and inexpensive synthesis of dienes 1 and 2 has been developed via a four-step procedure starting with benzenethiol and the corresponding cyclic ketone. No chromatography is required.     

Synthesis and some cycloaddition reactions of 2-(triisopropylsilyloxy)acrolein

[reaction: see text]2-(Triisopropylsilyloxy)acrolein is easily prepared by the reaction of triisopropylsilyl triflate and 2-methoxy-2-methyl-[1,3]dioxan-5-one in the presence of triethylamine. This dienophile reacts with selected dienes in the presence of catalytic amounts of scandium triflate to afford products that are formally 4 + 3 cycloadducts. An exception is seen in the case of butadiene, where only a 4 + 2 cycloadduct is observed.     

Hydroboration of terpenes—VIII: Cyclic hydroboration of d-(+)-limonene. A stereoselective synthesis of d-(−)-(1R, 2R, 4R)-limonene-2,9-diol and d-(−)-(1R, 2R, 4R)-carvomenthol

d-(+)-Limonene can be converted into the corresponding bicyclic organoborinate intermediate, B-methoxy-4,8-dimethyl-2-borabicyclo[3.3.1]nonane, by cyclic hydroboration with borane in THF, followed by methanolysis, and distillation of the product. Alternatively, cyclic hydroboration of d-(+)-limonene with thexylborane provides the related bicyclic organoborane intermediate, B-thexyl-4,8-dimethyl-2-borabicyclo[3.3.1]nonane. Oxidation of the respective intermediates produces d-(?)-(1R, 2R, 4R)-limonene-2,9-diol. Protonation of the bicyclic thexyl intermediate, followed by oxidation, provides d-(?)-(1R, 2R, 4R)-carvomenthol. These results suggest that the cyclic hydroboration of dienes can provide a valuable means for controlling the exact site of hydroboration, leading to a stereoselective synthesis of alcohols.     

Preparation of 2-Alkyl- and 2-Acylpropenals from 5-(Trifluoromethanesulfonyloxy)-4H-1,3-dioxin: A Versatile Acrolein α-Cation Synthon

5-(Trifluoromethanesulfonyloxy)-4H-1,3-dioxin (3) participates in a variety of nucleophilic substitution reactions with cuprate reagents or in palladium catalyzed cross-coupling reactions to provide 5-substituted-4H-1,3-dioxins 5. Upon thermolysis, these compounds undergo facile retrocycloaddition reactions to generate the corresponding 2-substituted acroleins which, if necessary, can be trapped in situ with dienes or heterodienophiles. In particular, the heretofore unknown 2-acylacroleins can be generated using this methodology and trapped with enol ethers to afford 5-acyl-3,4-dihydro-2H-pyrans (6g,h), a substructural unit common to many natural products.     

Ring Opening Three-Carbon Extension of 2-Carboethoxycyclo-Alkanones with 3-Bromo-1-(p-Tolylsulfonyl)Propene

Reaction with 1,8-diazabicyclo[5,4,0]undec-7-ene (DBU) of 2-[3-(p-tolylsulfonyl)-2-propenyl]-2-carboethoxycycloalkanones, derived from 2-carboethoxy-2-sodiocycloalkanones and 3-bromo-l-(p-tolylsulfonyl)propene, caused ring opening three-carbon extension in ethanol and three-carbon ring expansion in benzene to produce terminal dienes and cyclic dienes, respectively.     

Reactions of 3-(Prop-2-enylidene)azetidin-2-ones with 4,5-Dihydro-3H-1,2,4-triazole-3,5-diones

The 3-(2-propenylidene)-β-lactams 1a–c react as semicyclic dienes with the dihydrotriazole-diones 2 in a stereoselective fashion leading to the cycloadducts 3 . The 3′,3′-disubstituted derivative 4 gives no [4 + 2]-cycloaddition products but forms the adducts 5 and 6 . Sterochemistry and reaction pathways are discussed.     

Yttrium-catalyzed cis-1,4-Selective Polymerization of 2-(4-Halophenyl)-1,3-butadienes and Their Copolymerization with Isoprene

Polymerization of 2-(4-halophenyl)-1,3-butadiene(2-XPB) and their copolymerization with isoprene using a yttrium catalyst have been examined. The β-diketiminato yttrium bis(alkyl) complex(1) activated by [Ph_3 C][B(C₆ F₅)₄] and Ali Bu3 shows high cis-1,4-selectivity(>98%) for the polymerization of 2-XPB(2-XPB = 2-FPB, 2-Cl PB and 2-Br PB) to afford halogenated plastic poly(dienes) with glass transition temperatures of30–55 ℃. Moreover, the copolymerization of 2-XPB with isoprene(IP) has also been achieved by this catalyst, and the insertion ratios of 2-XPB can be facilely tuned in a full range of 0%–100% simply by changing the 2-XPB-to-IP ratio. Quantitative hydrogenation of cis-1,4-poly(2-XPB) results in perfect alternating ethylene-halostyrene copolymers, and an alternating copolymer of 4-vinylbenzoic acid with ethylene is obtained by a consecutive reaction of ethylene-4-bromostyrene copolymer with ⁿBu Li, CO₂ and HCl.     

Lithiation of 3-(Acylamino)-2-unsubstituted-, 3-(Acylamino)-2-ethyl-, and 3-(Acylamino)-2-propyl-4(3H)-quinazolinones: Convenient Syntheses of More Complex Quinazolinones(1)

3-(Pivaloylamino)- and 3-(acetylamino)-4(3H)-quinazolinones react with alkyllithium reagents to give 1,2-addition products in very good yields. Lithiation takes place with LDA and is regioselective at position 2. The lithium reagents thus obtained react with a variety of electrophiles to give the corresponding substituted derivatives in very good yields. Reactions of the lithium reagents with iodine give oxidatively dimerized cyclic structures. 3-(Pivaloylamino)- and 3-(acetylamino)-2-ethyl-4(3H)-quinazolinones and 3-(pivaloylamino)- and 3-(acetylamino)-2-propyl-4(3H)-quinazolinones are lithiated at the benzylic position with LDA. The lithium reagents so produced also react with a variety of electrophiles to give the corresponding 2-substituted-4(3H)-quinazolinone derivatives in very good yields. However, lithiation of 3-(acylamino)-2-(1-methylethyl)-4(3H)-quinazolinones was unsuccessful, as were lithiations of compounds having a diacetylamino group at position 3. The amide groups have been cleaved in good yield under basic or acidic conditions from some of the products to provide access to the free amino compounds.     

2-(三甲氧基苯基)色胺盐酸盐的合成

2,3,4-及3,4,5-三甲氧基苯乙酮苯腙在多聚磷酸存在下进行Fischer反应,可生成相应的吲哚(1_a,1_b),但2,4,6-三甲氧基苯乙酮苯腙必须用无水氯化锌催化环化才能得到相应的吲哚(1_c)。1_a、1_b、1_c经Vilsmier反应生成相应的吲哚-3-醛(2_a,2_b,2_c);经与硝基甲烷缩合得到相应的2-(三甲氧基苯基)-3-(2-硝基乙烯基)吲哚(3_a,3_b,3_c);3_a及3_b用LiAlH₄还原即可制备成相应的色胺盐酸盐(4_a和4_b),3_b还被制成苦味酸盐(4_b)。     

Racemic and asymmetric Diels-Alder reactions of 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes

Achiral and chiral 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes were prepared from readily available starting materials. Although more stable than the parent 1-amino-3-siloxy dienes, the 1-(2-oxazolidinon-3-yl)-3-siloxy-1,3-butadienes are still very reactive in Diels-Alder reactions, somewhat more than 1,3-dialkoxy-1, 3-butadienes (e.g., Danishefsky's diene). The cycloadditions of the achiral and chiral dienes with several different dienophiles were examined. The reactions proceeded in good yield, with modest to high endo selectivity. The chiral dienes exhibited excellent facial selectivity in cycloadditions with alpha-substituted acroleins, maleic anhydride and N-phenylmaleimide. Upon reduction and hydrolysis of the cycloadducts, substituted cyclohexenones were obtained with ee's ranging from 22% to >98%.     

Synthesis of Delta(1)-1,2-diazetines via a Diels-Alder cycloaddition approach

[reaction: see text] A novel method for the synthesis of Delta(1)-1,2-diazetines is presented. Diels-Alder cycloaddition of dienophile 4 with five dienes afforded cycloadducts in good to excellent yields. Four of the obtained cycloadducts were converted to the corresponding diazetines.     

Enantiomeric separation of novel anticancer agent 5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one

The enantiomers of 5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one, a novel anticancer agent, were separated by derivatisation with caronaldehyde, separation of the resulting diastereoisomers of the corresponding esters by silica gel column chromatography and regeneration of alcohols (S)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one and (R)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-one under aqueous conditions. The absolute configuration of the enantiomers was determined by 1H NMR studies of the corresponding Mosher esters. Alternatively, the enantiomers were separated by preparative HPLC to collect the (S)- and (R)-5-hydroxy-3-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)-cyclopent-2-en-1-ones with high purity which was comparable with that obtained by the chemical method. The details of these methods have been presented herein.     

The Diels-Alder Reaction of Dienes Derived from Substituted 3-(Phenyl-Thio)-3-Sulfolenes

Substituted 3-(phenylthio)-3-sulfolenes (3) and (4) are good precursors for 2-(phenylthio)-1,3-butadienes (5) and (6). The Diels-Alder reaction of the dienes derived from (3) and (4) with various dienophiles was studied. It was found that heating of sulfolenes (3) with methyl propiolate and N-phenylmaleimide afforded the Diels-Alder adducts of (5) directly and with complete regio- and stereospecificity. The same reaction with methyl vinyl ketone gave a mixture of endo and exo addition products. If sulfolenes (3) were first converted to the dienes (5) using lithium aluminum hydride and then reacted with methyl vinyl ketone in the presence of anhydrous zinc chloride, the stereoselectivity could be improved. Sulfolenes (4) also underwent cycloreversion/cycloaddition with methyl acrylate, methyl vinyl ketone, and N-phenylmaleimide, but gave mostly the double bond-isomerized cycloaddition products. The regiochemistry of cycloaddition was delicately dependent on the dienophiles used.     

Synthesis and spatial structure of 4-(2-hydroxyethyl)-5-(2-hydroxyphenyl)-2H-1,2,4-triazolo-3(4H)-thione

By reaction of 2-vinyloxyethyl isothiocyanate with salicylic acid hydrazide a synthesis of the corresponding thiosemicarbazide was performed. Alkaline hydrolysis of the latter led to an intramolecular heterocyclization into 1,2,4-triazole derivative. When cyclization was carried out in the water-alkali medium, 2-vinyloxyethyl fragment was shown to be hydrolyzed to form 4-(2-hydroxyethyl)-5-(2-hydroxyphenyl)-2H-1,2,4-triazolo-3(4H)-thione, whose spatial structure was established by XRD analysis.     

Synthesis and deprotonation of 2-(pyridyl)phenols and 2-(pyridyl)anilines

2-(2- and 3-Pyridyl)anilines (1, 2), 2,2-dimethyl-N-[2-(2- and 3-pyridyl)phenyl]propanamides (3, 4), and 2-, 3- and 4-(2-methoxyphenyl)pyridines (7-9) are readily synthesized using cross-coupling reactions. Whereas the amines 1, 2 undergo side reactions, the corresponding amides 3, 4 are deprotonated with lithium 2,2,6,6-tetramethylpiperidide (LTMP): the compound 3 at C6' under in situ quenching, and the compound 4 at C4'. When the ether 7 is subjected to the same reagent, lithiation occurs at C6'.