Reaction of 4-methyl, 4-phenyl, and 4-hydrogen substituted 1-lithio-1,3-butadienes with aldehydes: preparation of multiply substituted cyclopentadienes

Reaction of aldehydes with 1-lithio-1,3-butadiene reagents possessing a methyl substituent, a phenyl substituent or a hydrogen at position 4 of the butadienyl skeletons was studied. Polysubstituted cyclopentadiene derivatives were obtained in high yields upon hydrolysis using strong acidic solution. Reaction mechanism study revealed that these cyclopentadienes were formed via an acid-promoted cyclization of conjugated dienols. Thus, stereodefined all-cis substituted dienols or a wide diversity of substituted cyclopentadienes can be obtained from the same 1-lithio-1,3-butadiene reagent and aldehyde by adjusting the hydrolysis conditions.     

Selective synthesis of multiply substituted 7-norbornenone derivatives or Diels-Alder cycloadducts from 1,2,3,4-tetrasubstituted 1,3-butadienes and maleic anhydride with or without Lewis acids

Reactions of 1,2,3,4-tetrasubstituted 1,3-butadienes with maleic anhydride and other dienophiles were investigated with or without addition of Lewis acid. When the silylated 1,3-butadienes, such as 1,4-bis(trimethylsilyl)-1,3-butadienes or 1-trimethylsilyl-1,3-butadienes, were treated with maleic anhydride in the presence of 2 equiv of AlCl₃, multi-substituted 7-norbornenones of well-defined exo,exo-disubstituted patterns were produced by an unprecedented and synthetically useful tandem process. Although some tetrasubstituted 1,3-butadienes could react directly with maleic anhydride under relative harsh conditions to afford Diels-Alder cycloadducts, the reactions, in the presence of 1 equiv of AlCl₃, afforded the corresponding cycloadducts in higher yields under mild conditions. These results showed that the size and substitution pattern of substituents on the butadienyl skeleton played a very important role in the reactivity of butadienes as a partner for the Diels-Alder reaction and Lewis acid could promote and/or realize the process of a Diels-Alder reaction.     

CuCl-mediated tandem CO insertion and annulation of 1,4-dilithio-1,3-dienes: formation of multiply substituted cyclopentadienones and/or their head-to-head dimers

Mediated by CuCl, 1,4-dilithio-1,3-dienes reacted with carbon monoxide (CO) to generate multi-substituted cyclopentadienones and/or their head-to-head dimers, via tandem CO insertion and intra/intermolecular cycloaddition of organocopper compounds.     

Cleavage of C-Si bond by intramolecular nucleophilic attack: lithiation-promoted formation of siloles from 1-bromo-4-trisubstituted silyl-1,3-butadiene derivatives

Lithiation of 1-bromo-4-trisubstituted silyl-1,3-butadiene derivatives with t-BuLi afforded substituted siloles in high yields. Cleavage of one of the three C-Si bonds took place via intramolecular nucleophilic substitution. Selective cleavage was observed when the silyl group possessed different substituents. Results showed that vinyl and phenyl substituents on Si were substituted much more easily than methyl groups, whilst a methyl group was exclusively deleted from an i-Pr-SiMe₂ moiety.     

The skeletal rearrangement of gold- and platinum-catalyzed cycloisomerization of cis-4,6-dien-1-yn-3-ols: pinacol rearrangement and formation of bicyclo[4.1.0]heptenone and reorganized styrene derivatives

With gold and platinum catalysts, cis-4,6-dien-1-yn-3-ols undergo cycloisomerizations that enable structural reorganization of cyclized products chemoselectively. The AuCl3-catalyzed cyclizations of 6-substituted cis-4,6-dien-1-yn-3-ols proceeded via a 6-exo-dig pathway to give allyl cations, which subsequently undergo a pinacol rearrangement to produce reorganized cyclopentenyl aldehyde products. Using chiral alcohol substrates, such cyclizations proceed with reasonable chirality transfer. In the PtCl2-catalyzed cyclization of 7,7-disubstituted cis-4,6-dien-1-yn-3-ols, we obtained exclusively either bicyclo[4.1.0]heptenones or reorganized styrene products with varied substrate structures. On the basis of the chemoselectivity/structure relationship, we propose that bicyclo[4.1.0]heptenone products result from 6-endo-dig cyclization, whereas reorganized styrene products are derived from the 5-exo-dig pathway. This proposed mechanism is supported by theoretic calculations.     

Beckmann and cyclization reactions of δ-oxo-α,β-unsaturated ketoximes obtained from pyrylium salts and hydroxylamine. formation of 2-aryl(or alkyl)amino-4,6-disubstituted pyrylium salts

The reaction of 2,4,6-trisubstituted pyrylium salts 1 with hydroxylamine gave regio- and stereo-selectively 1,3,5-trisubstituted 2-cis-pentene-1,5-dione 1-oximes 4. On cyclization, 3,5,5-trisubstituted 2-isoxazolines 6 and 2,4,6-trisubstituted pyridine 1-oxides 5 were obtained, originating in the antilsyn stereoisomers of oxime 4, respectively. Beckmann reaction of keto-ketoximes 4 with thionyl chloride unexpectedly gave 2-aryl (or alkyl) amino-4,6-di-substituted pyrylium salts 7, the first example of rearrangement/cyclization involving carbonylic oxygen as terminator. Crystallographic data are provided for (Z)-N-t-butyl-3,6,6-trimethyl-2-heptenecarboxamide 13b.     

A novel synthesis of silyl enol ethers from α-silylbenzylthiols and carboxylic acid derivatives via C---C bond formation; thermal rearrangement of S-α-silylbenzyl thioesters

A new procedure for the synthesis of silyl enol ethers from S-α-silylbenzyl thioesters without need for either bases or catalysts via C---C bond formation is described. Solutions of S-α-silylbenzyl thioesters were simply heated at 180°C for 24 h in a sealed tube to give silyl enol ethers in good yields with high stereoselectivity. Cyclization of the dipoles generated by thermal rearrangement of the silyl group and elimination of sulfur afforded silyl enol ethers.     

Diazepines[1,4] annelated with indoline and maleimide from 3-(di)alkylamino-4-(indol-1-yl)maleimides: mechanism of rearrangement and cyclization

The mechanism of cyclization of 3-(di)alkylamino-4-(indol-1-yl)maleimides to diazepine[1,4] derivatives was elucidated using deuterium labeled precursors.     

Chemo-, regio- and stereoselective 1,3-dipolar cycloaddition of C-aryl-N-phenylnitrones over 3,5-bis(arylidene)-1-methylpiperidin-4-ones: synthesis of highly substituted novel spiro-isoxazolidines

1,3-Dipolar cycloaddition of C-aryl-N-phenylnitrones to 3,5-bis-(arylidene)-1-methylpiperidin-4-ones affords novel mono- and bis-spiroisoxazolidines in moderate yields. In general, this reaction predominantly yields mono-spiroisoxazolidine, wherein the oxygen of the nitrone is linked to the β-carbon of the benzylidene moiety, while 3,5-bis-(2-chloro- and 3-nitro-benzylidene)-1-methylpiperidin-4-ones afford predominantly bis-spiroisoxazolidines. The cycloaddition of mono-spiroisoxazolidines occurs with facial diastereoselectivity to furnish bis-spiroisoxazolidines. The nitrogen in the heterocyclic ring of the 3,5-bis-(arylidene)-1-methylpiperidin-4-ones facilitates the cycloaddition through transannular (NCO) and/or homoconjugative (NCC) interactions.     

Novel synthesis of 7-fluoro-8-(trifluoromethyl)- 1H-1,6-naphthyridin-4-one derivatives: intermolecular cyclization of an N-silyl-1-azaallyl anion with perfluoroalkene and subsequent intramolecular skeletal transformation of the resulting pentasubstituted pyridines

In this study, fluorine-containing pentasubstituted pyridine derivatives 9a-m were prepared regioselectively in good yields by the intermolecular cyclization of a variety of N-silyl-1-azaallylic anion intermediates 7, which were generated from a functionalized silane 5 and an aromatic/aliphatic nitrile 6 with perfluoroalkene 8. Also, 7-fluoro-8-(trifluoromethyl)-1H-1,6-naphthyridin-4-one derivatives 11a-k were synthesized in excellent yields by the subsequent base-promoted intramolecular skeletal transformation of the resulting pyridine derivatives 10a-k.     

Stereochemistry of terpene derivatives. Part 8: synthesis of novel terpenoids from (1S,4R)- and (1R,4S)-fenchone and their comparative odour characteristics

O-alkylation of (+) and (−)-fenchone oximes with various alkyl halides led to 20 novel ethers. Better results were obtained when mild reaction conditions were employed (i.e., aprotic, polar solvent and room temperature). The hydrolytic kinetic resolution of the O-glycidyl derivative was carried out using cobalt-salen catalysts. The best results were obtained when using (−)-(R,R)-catalyst: (−)-(R)-isomer was obtained with >90% de. The use of a (+)-(S,S)-catalyst gave the (−)-(S)-epoxide with only 67% de. However, the (S)-epoxide was obtained with >90% de when the (−)-(R)-diol was subjected to the Mitsunobu reaction. Significant fragrance diversity was observed between the homologous series of fenchone oxime ethers. More agreeable are scents of ethers derived from (−)-fenchone oxime. Their odours range from turpentine like and resinous to vegetable, floral or woody whereas the scents of (+)-ethers range from turpentine, resinous to onion like and slightly floral.     

Synthesis of novel 1‐substituted [1,3]thiazolo[3,2‐a]‐[1,5]benzodiazepine derivatives from 1,5‐benzodiazepine‐2‐thiones and α‐halogen carbonyl compounds

A number of substituted 4H,5H,6H‐thiazolo[3,2‐a][1,5]benzodiazepinium salts 2a‐h, 5, 9 , which are based on the novel thiazolobenzodiazepine system, were prepared by condensation‐cyclization of 1,5‐benzodiazepine‐2‐thiones 1a‐f, h, 4 with α‐haloketones, as well as with α‐bromoacetaldehyde diethyl acetal. The structure and stereochemistry of the ring system obtained were investigated by ¹H and ¹³C nmr spectroscopy: the additional heterocyclic nucleus was found to appreciably influence the conformational mobility of the heptatomic ring. Upon treatment of salt 2d with alkali the presence of the base enamine structure in solution has been postulated.