Hydroacylation of 2-butyne from the alcohol or aldehyde oxidation level via ruthenium catalyzed C-C bond forming transfer hydrogenation

Under the conditions of ruthenium catalyzed transfer hydrogenation, 2-butyne couples to alcohols 1a-1j to deliver α,β-unsaturated ketones 3a-3j in good to excellent isolated yields with complete E-stereoselectivity. Under identical conditions, aldehydes 2a-2j couple to 2-butyne to provide an identical set of α,β-unsaturated ketones 3a-3j in good to excellent isolated yields with complete E-stereoselectivity. Nonsymmetric alkyne 4a couples to alcohol 1d or aldehyde 2d in good yield to deliver enone 3k as a 5:1 mixture of regioisomers. Thus, intermolecular alkyne hydroacylation is achieved from the alcohol or aldehyde oxidation level. In earlier studies employing the same ruthenium catalyst under slightly different conditions, alkynes were coupled to carbonyl partners from the alcohol or aldehyde oxidation level to furnish allylic alcohols. Therefore, under the conditions of C-C bond forming transfer hydrogenation, all oxidation levels of substrate (alcohol or aldehyde) and product (allylic alcohol or α,β-unsaturated ketone) are accessible.     

Stereoselective synthesis of highly substituted trans-2,3-dihydrofuran and trans-1,2-cyclopropane derivatives containing sulfonyl groups

trans-2,3-Dihydrofuran derivatives 3 and trans-1,2-cyclopropane derivatives 4 were prepared with high chemoselectivity and moderate overall chemical yield by the reaction of α,β-unsaturated sulfones 1 with arsonium bromides 2 in the presence of potassium carbonate. The structures of products obtained were identified by IR, MS, ¹H NMR, elemental analysis, and X-ray diffraction analysis.     

A direct synthesis of α-(hydroxymethyl) and α-alkyl-vinyl alkyl ketones

Reaction of 2,4-diketoesters 3a-c with aqueous formaldehyde using potassium carbonate solution as base affords the corresponding α-methylene-β-hydroxyalkanones 4a-c which provide a route to α,β-unsaturated alkyl ketones 6a-e via coupling of α-acetoxymethyl alkyl vinyl ketone 5a with Grignard reagents in the presence of a catalytic amount of LiCuBr₂ at low temperature.     

Prepackaged Ramberg-Bäcklund reagents: useful tools for organic synthesis

The synthesis and reactions of several α,β-unsaturated chloromethyl sulfones is presented, for example [(chloromethyl)sulfonyl]-1,3-propadiene (4), [(chloromethyl)sulfonyl]ethene (5), [(dichloromethyl)sulfonyl]ethene (6) and (E,Z)-1,2-bis[(chloromethyl)sulfonyl]ethene (7). These compounds serve as ‘prepackaged’ Ramberg-Bäcklund reagents, which following an appropriate first step, such as Diels-Alder addition, react with base giving Ramberg-Bäcklund products.     

A practical and efficient synthesis of (E)-β-aryl-α,β-unsaturated amides

In this paper, we report a one-step convergent synthesis of (E)-β-monosubstituted α,β-unsaturated amides 3 from α-sulfonyl acetamide 1 and benzyl bromide derivatives 2.     

Two-carbon homologation of ketones via sily ketene acetals: Synthesis of α,β-unsaturated acids and α-trimethylsilyl δ-ketoacids

The reaction of C,O,O-tris(trimethylsilyl)ketene acetal 1 with saturated, cyclic and aromatic ketones 2 proceeds smoothly in the presence of titanium chloride to give (E)-α,β-unsaturated carboxylic acids 3 with fairly good stereoselectivity. With α,β-unsaturated ketones 4, α-trimethylsilyl δ-ketoacids 5 (syn + anti) are obtained according to Michael-type 1,4 addition. These diastereoisomers are separated and the configurations of 5a are achieved by X-ray molecular analysis.     

One-pot facile conversion of Baylis-Hillman adduct into N-alkyl 3-(E)-alkylidene-5-substituted sulfonylpiperidine-2,6-dione. Formal synthesis of tacamonine

A stepwise [3+3] strategy to N-alkyl 3-(E)-alkylidene-5-substituted sulfonylpiperidine-2,6-dione 1 used various N-alkyl α-substituted sulfonylacetamides 2 and α,β-unsaturated esters 3 as starting materials. α,β-Unsaturated esters 3 were generated by Baylis-Hillman reaction. A ring closure mechanism was proposed for the reactions. This method provides a convenient formal synthesis of tacamonine.     

Features and applications of reactions of α,β-unsaturated N-acylbenzotriazoles with amino compounds

Promoted by triethylamine, α,β-unsaturated N-acylbenzotriazoles reacted with amino compounds in a variety of ways. Thus, N-cinnamoylbenzotriazoles reacting with aromatic amines afforded novel addition products β-benzotriazolyl amides 3, which might be normally formed from the alternative but unknown 1,4-addition of benzotriazole to N-cinnamoylamides. The type 3 compounds could also result from the reaction between N-crotonoylbenzotriazole and aliphatic amines. However, normal 1,4-addition could occur between α,β-unsaturated aliphatic N-acylbenzotriazoles and aromatic amines, leading to β-amino N-acylbenzotriazoles 4 in good yields. In addition, exclusive 1,2-addition of aliphatic amines to N-cinnamoylbenzotriazoles gave excellent yields of cinnamides 5. Accordingly, three possible routes were proposed to rationalize the formation of compounds 3-5. Finally, with o-phenylenediamine and o-aminothiophenol as the substrates, the 1,4- and 1,2-addition to α,β-unsaturated N-acylbenzotriazoles could take place concurrently and the corresponding heterocycles 1,5-benzodiazepine-2-one and 1,5-benzothiazepine-4-one were constructed, respectively.     

Diastereoselective addition of nitro compounds to α,β-unsaturated γ-butyrolactones

Herein, we report our results on the diastereoselective addition of nitro compounds to α,β-unsaturated γ-butyrolactones, which afforded the corresponding Michael adducts 9-17 in moderate to good yields and good to excellent diastereoisomeric ratio. A one-pot conversion of α,β-unsaturated γ-butyrolactones 7 and 8 to the corresponding trisubstituted keto-γ-butyrolactones 24 and 25 via a tandem Michael-Nef protocol is also described.     

Enantioselective organocatalyzed cascade reactions to highly functionalized quinolizidines

An organocatalyzed one-pot Michael addition-Pictet-Spengler sequence of β-ketoamides and α,β-unsaturated aldehydes was developed, which provided access to highly substituted indolo[2,3-α]quinolizidines and benzo[α]quinolizidines in moderate to good yields and good to excellent enantioselectivities. For aromatic α,β-unsaturated aldehydes 1a-j products 10a-r containing a stable enol configuration were obtained.     

Efficient synthesis of fluorinated α- and β-amino nitriles from fluoroalkylated α,β-unsaturated imines

A simple and efficient synthesis of fluoroalkylated α-amino nitrile (4) derivatives by regioselective 1,2-addition of trimethylsilyl cyanide to fluoroalkylated α,β-unsaturated imines (1) is described. Fluoroalkylated β-amino nitriles (7) are also prepared by regioselective 1,2-addition of α-carbanions derived from acetonitrile to fluoroalkylated α,β-unsaturated imines (1). Fluoroalkylated α-(4) and β-amino nitriles (7) are also prepared through an ‘one pot’ procedure by reaction of enaminophosphonate 2 with BuLi, addition of aldehydes and subsequent addition of either trimethylsilyl cyanide or α-carbanion derived from acetonitrile. Basic hydrolysis of α-(4) and β-amino nitriles (7) gives fluoroalkylated α-(5) and β-amino acids (8).     

An easy ABD→ABCD strategy to indolo[2,3-a]quinolizin-4-one. Synthesis of deplancheine and yohimbane

The efficient synthesis of indolo[2,3-a]quinolizin-4-ones 2 is described in two steps via formal [3+3] cycloaddition reaction of α-sulfonyl tryptaminylacetamide 4 with various α,β-unsaturated esters 5 and the regioselective reduction of the resulting glutarimides 3 with sodium borohydride then sequent further dehydrated cyclization in the presence of boron trifluoride etherate. The useful building block is applied to synthesize deplancheine (1a) and yohimbane (1b).     

1,7-Electrocyclisations of stabilised azomethine ylides

Ester-stabilised α,β:γ,δ-unsaturated azomethine ylides 9 were generated by the deprotonation method from isoquinolinium salts 8. 1,7-Electrocyclisation of these dipoles followed by a 1,5-hydrogen shift, gives tetrahydro[5,6]azepino[2,1-a]isoquinolines 10.     

Synthesis of a para-quinone macrolactam related to geldanamycin by ring closing metathesis

Model studies conducted with the α,β,γ,δ-unsaturated 3-alkenyl-2,4,5-trimethoxyanilides 11 revealed that a ring closing metathesis (RCM) of these compounds is possible if the ansa chain contains more than 14 atoms. The (Z)-configurated products 12c-e were obtained in good yields (77-87%) and with perfect simple diastereoselectivity. Since the oxidation of the 2,4,5-trimethoxyanilides led predominantly to undesired ortho-quinones such as 15 or to para-azaquinones such as 16 the macrocyclic 2,5-di-iso-propoxy-4-methoxyanilide 22 was prepared. The iso-propyl protecting groups could be selectively cleaved and the intermediate para-hydroquinone oxidized on air to the desired para-quinone 2 (86% yield). The compound shows some key features (macrolactam ring with the same ring size, α,β,γ,δ-unsaturated anilide, para-quinone) of geldanamycin.     

Stereoselective synthesis of (6S) and (6R)-5,6-dihydro-6-[(2R)-2-hydroxy-6-phenylhexyl]-2H-pyran-2-one and their cytotoxic activity against cancer cell lines

Stereoselective total synthesis of α,β-unsaturated lactone (1a), isolated from Ravensara crassifolia, has been achieved efficiently starting from chiral 2,3-O-isopropylidene-d-glyceraldehyde (3) followed by asymmetric allylation and ring-closing metathesis. The antiproliferative activities of compounds 1a, 1b and the unusual bicyclic compound 2 were evaluated against three-cancer cell lines, THP-1 and U-937 (leukemia) and A-375 (melanoma).     

Synthesis and hetero-Diels-Alder reactions of (E)-α-perfluoroalkanesulfonyl-α,β-unsaturated ketones

Catalyzed by ammonium acetate, the Knoevenagel reactions of β-keto perfluoroalkanesulfones 1 with aromatic aldehydes 2 afforded α-perfluoroalkanesulfonyl-α,β-unsaturated ketones 4 in moderate to good yields. The possible mechanism for the reactions was proposed. These fluorine-containing α,β-unsaturated ketones, which are electron-poor 1-oxa-1,3-butadienes, could be used in inverse electron demand hetero Diels-Alder (HDA) reaction with electron-rich olefins to give tetrasubstituted dihydropyrans 6 in quantitative yields.     

New synthetic technology for the construction of N-hydroxyindoles and synthesis of nocathiacin I model systems

A new synthetic method providing expedient access to a wide range of polyfunctionalized N-hydroxyindoles (IV) is reported. These unique constructs are assembled by nucleophilic additions to in situ generated α,β-unsaturated nitrones (III) through carbon-carbon and carbon-heteroatom bond formation. The new synthetic technology was applied to the synthesis of nocathiacin I (1) model systems (2 and 3a-c) containing the N-hydroxyindole structural motif.     

Copper-catalyzed addition reaction of γ,γ-dialkoxyallylic zirconium species with imines

In the presence of CuCN, reaction of γ,γ-dialkoxyallylic zirconium species 1 with imines proceeded at the γ-position of 1 to give gem-dialkoxyhomoallylic amines 3 in high yield. In this reaction, γ,γ-dialkoxyallylic zirconium species 1 acts as an α,β-unsaturated acyl anion equivalent.     

The intramolecular conjugate addition of benzylamine to a d-glucose derived α,β-unsaturated ester: an efficient synthesis of trihydroxylated pyrrolidine alkaloids as potential glycosidase inhibitors

A short and efficient synthesis of 1,4,5-trideoxy-1,4-imino-l-xylo-hexitol 2a and 1,4,5-trideoxy-1,4-imino-d-arabino-hexitol 2b is reported using the intramolecular conjugate addition of in situ generated benzylamine to the α,β-unsaturated ester 4, derived from d-glucose, as the key step.     

Diastereoselective addition of planar N-heterocycles to vinyl sulfone-modified carbohydrates: a new route to isonucleosides

Michael-type addition reactions of planar N-heterocycles at the C-2 positions of vinyl sulfone-modified carbohydrates provide an efficient and general route for the carbon-N-heterocycle bond formation. Therefore, the addition pattern of planar heterocycles, such as imidazole, triazole, thymine, and adenine to 3-C-phenylsulfonyl-hex-2-enopyranosides (1α/1β) and 3-C-p-toluenesulfonyl-pent-2-enofuranosides (2α/2β) was studied for developing a general methodology for the synthesis of new classes of isonucleosides possessing a carbon-N-heterocycle linkage at C-2 positions of furanosyl and pyranosyl sugars. To a great extent, the anomeric configurations of the starting vinyl sulfones play crucial roles in deciding the diastereoselectivity of addition of heterocycles. However, the trityl protected 3-C-p-toluenesulfonyl-hex-2-enopyranosides (33α/33β) were judged to be more practical starting materials for desulfonylation and deprotection for the synthesis of a new class of thymine and adenine deoxyisonucleosides.