Diastereoselective michael addition of nitrogen and sulfur-nucleophiles to α,β-unsaturated δ-thiolactams

5,6-Dihydropyridine-2-thiones 2 are synthesized from 5,6-dihydropyridin-2-ones 1 and Lawesson reagent. Stereoselective Michael-like addition of amines, methylhydrazine or functionalized thiols affords trans piperidine-2-thiones 5 with the corresponding heterosubstituent in position 4 as major products. The configuration of the adducts 5 was determined by nmr-techniques.     

Applications of 1,4-addition of grignard reagents to α,β-unsaturated acid derivatives. III—configuration studies of α,β-diaryl-α,β-dialkylpropionitriles

The configuration of twenty-four different α,β-diaryl-α,β-dialkylpropionitriles has been determined using nuclear magnetic resonance spectra. The erythro form showed greater deshielding of the methine hydrogen and alkyl groups in its spectra than the corresponding threo isomer. The former, however, showed less deshielding of the aryl groups than the threo isomer. Infrared spectra were not suitable for assignments of configuration.     

Regiospecific Acylation,Alkylation, and Aldol Condensation using magnesium enolates resulting from the conjugate addition of grignard reagents to α, β-unsaturated ketones

The magnesium 3,3-dimethylcyclohex-1-enolate 1i , formed in the copper catalyzed addition of methylmagnesium iodide to 3-methylcyclohex-2-enone, has been subjected to regiospecific electrophilic reactions such as acylation, alkylation, and aldol condensation in order to find a new access to the damascones, ionones and carotenoids. By way of illustration a new synthesis of γ-damascone is described.     

1,4-Conjugate addition of allyltrimethylsilane to α,β-unsaturated ketones

α,β-Unsaturated ketones smoothly undergo conjugate addition with allyltrimethylsilane in the presence of a catalytic amount of elemental iodine under very mild and convenient conditions to afford the corresponding Michael adducts in high yields with high selectivity.     

Diastereoselective SmI2-mediated cyclisation of δ-oxo-α,β-unsaturated esters to cyclopropanols

In the presence of samarium diiodide and a proton source, δ-oxo-γ,γ-disubstituted-α,β-unsaturated esters readily cyclise with complete diastereocontrol to give anti-cyclopropanol products.     

The high resolution mass spectra of α,β-unsaturated and α-chloromercuri-α,β-unsaturated steroidal ketones

The high resolution mass spectra (500 eV) of some α,β-unsaturated steroidal ketones have been studied and compared with the spectra of the corresponding α-chloromercuri ketones. In the latter, the carbon-mercury bond frequently remains intact at the expense of the fission of two carbon-carbon bonds. The abundance of mercury-containing ions allows the use of the mercury atom fingerprint in confirming ring B fragmentation of the steroid nucleus at C(6)–C(7) and C(9)–C(10) for 5α-androst-1-ene-3,17-dione, 1,4-androstadiene-3,17-dione and their 2-chloromercuri derivatives; and at C(7)–C(8) and C(9)–C(10) for 1,4,6-androstatriene-3,17-dione, 1,4,6-androstarien-17 β-ol-3-one and their 2-chloromercuri derivatives. 2-Chloromercuri-1,4,6-androstatriene-3,17-dione and 2-chloromercuri-1,4,6-androstatrien-17 β-ol-3-one also give an abundant ion as the result of ring C fragmentation at C(8)–C(14) and C(11)–C(12), the chloromercuri group being replaced by a hydrogen atom. This ring C cleavage gives the only recognizable distinctive fragmentation ion for 1,4,6-pregnatriene-3,20-dione and 2-chloromercuri-1,4,6-pregnatriene-3,20-dione. For most of the mercurated steroids, the low resolution mass spectra (70 eV) are reported. In these spectra, the fragmentation patterns are similar to those obtained using the higher ionization energy employed for the high resolution spectra.     

Synthesis of α,β-unsaturated oxathiolanes

The formation of α,β-unsaturated oxathiolanes 2 from α,β-unsaturated carbonyl derivatives was achieved selectively and in high yields using the heterogeneous catalyst APSG·HCl.     

Lipophilic Functionalized Cobyrinic-Acid Derivatives. Part 1. Cobester α-monoacids (α,α,α,β,β,β-hexamethyl α-hydrogen Coα, Coβ-dicyanocobyrinates)

The four α,α,α, β,β,β,-hexamethyl α-hydrogen Coα, Coβ-dicyanocobyrinates 2b, d–f , with a free b-, d-, e-, and f-propionic-acid function, respectively, were prepared by partial hydrolysis of heptamethyl Coα, Coβ-dicyanocobyrinate (cobester; 1 ) in aqueous sulfuric acid. The cobester monoacids 2b, d–f were obtained as a ca. 1:1:1:1 mixture which was separated. The monoacids were purified by chromatography and isolated in crystalline form. The position of the free propionic-acid function was determined by an extensive analysis of 2b, d–f using 2D-NMR techniques; an analysis of the C,H-coupling network topology resulted in an alternative assignment strategy for cobyrinic-acid derivatives, based on pattern recognition. Additional information on the structure of the most polar of the four hexamethyl cobyrinates, of the b-isomer 2b , was also obtained in the solid state from a single-crystal X-ray analysis. Earlier structural assignments based on 1D-NMR spectra of the corresponding regioisomeric monoamides 3b, d–f (obtained from crystalline samples of the monoacids 2b, d–f ) were confirmed by the present investigations.     

Addition of trimethylsilylmethylmagnesium chloride to α, β-unsaturated carbonyls

Reactions of α,β-unsaturated carbonyl compounds with Me₃SiCH₂MgCl, prepared from chloromethyltrimethylsilane [1], were examined. Unlike its lithium counterpart (Me₃SiCH₂Li), which adds to α,β-unsaturatedketones in the 1,2-sense, the Grignard reagent afforts γ silanes via a 1,4-addition sequence. This tendency is accentuated by the addition of Cu₂Br₂. Addition of the Grignard reagent to α,β-unsaturated aldehydes gives the simple 1,2-addition products.     

Synthesis of α,β-unsaturated ketone from α-iodo ketone using photoirradiation

Irradiation of α-iodo ketone in hexane under a nitrogen atmosphere with a high-pressure mercury lamp (λ>300nm) at room temperature afforded the corresponding α,β-unsaturated ketones in good yield. This reaction affords a new, clean and convenient synthetic method for the α,β-unsaturated ketone.     

Palladium-catalyzed conjugate addition type reaction of 5-iodopyrimidines with α,β-unsaturated ketones

The reaction of various 5-iodopyrimidines with α,β-unsaturated ketones in the presence of palladium diacetate-triphenylphosphine complex in triethylamine are investigated. In the reaction of 2,4-dialkoxy(or alkylthio)-6-methyl-5-iodopyrimidine the addition of pyrimidine to the carbon? carbon double bond of α,β-unsaturated ketones occurs. In the case of other pyrimidines, according to the decrease of steric hindrance at the 5-position on the pyrimidine ring, the ratio of conjugate addition product was decreased and the usual olefinic substituted product was increased.     

The clemmensen reduction of α,β-unsaturated ketones

The deoxygenation of the α,β-unsaturated ketones (1) and (5) under the Clemmensen condition yielded the olefins (2) and (6) along with their respective dimers (3+4) and (8+9). The α , β-unsaturated ketone (13) under similar treatment yielded the olefin (14) in satisfactory yield but the dimer could not be characterized. The deoxygenation of the α,β-unsaturated ketones (10) and (16) under similar con- ditions afforded the olefins (12) and (15) respectively in satisfactory yield along with the rearranged olefins (11) and (17) respectively. Epox-idation of the olefin (17) followed by heating with p-toluenesulfonic acid yielded the ketone (18).     

β-lithiations of carboxamides. Synthesis of β-substituted-α,β-unsaturated amides

N-Methyl-2-methyl-3-(benzotriazol-l-yl)propanamide, on treatment with butyllithium forms a dianion which on treatment with alkyl and benzyl halides, aldehydes and ketones affords monosubstituted products; with ethyl p-toluate, a lactam is formed. The alkylated derivatives eliminate benzotriazole in the presence of base to afford trisubstituted α,β-unsaturated amides.     

Reactions of α,β-unsaturated ketones with cyanoacetamide

3-Aryl-1-phenyl-2-propen-1-ones Ia-f and aroylphenylacetylenes Va-d reacted under reflux for 3 hours with cyanoacetamide in the presence of sodium ethoxide to give the corresponding 4-aryl-3-cyano-6-phenyl-2-(1H)pyridones VI. However, when ketones Ia-e were refluxed with cyanoacetamide for one hour in the presence of sodium ethoxide or piperidine, they gave the corresponding 4-aryl-3-cyano-3,4-dihydro-6-phenyl-2-(1H)pyridones IIIa-e, which upon heating with selenium gave the corresponding 2-pyridones VI. The structures of the products are based on chemical and spectroscopic evidence.     

Condensation of 3-methylbenzoxazolinone with α,β-unsaturated acids

The reaction between 3-methylbenzoxazolinone and some unsaturated acids in PPA leads to mixtures of compounds, depending on the acid: 6-crotonyl- (or cinnamoyl)-3-methylbenzoxazolinones, 2,3-dihydro-2,5-(or 2,7)dioxo-3-methylcyclopenta[f]benzoxazoles and 6-(3-oxo-indanyl)-3-methylbenzoxazolinones. The structure of the products was established by ¹³C and ¹H nmr spectroscopy and (or) by independent synthesis. Possible mechanisms of the reaction are discussed; when competition is possible as in the last step of the cyclization, the benzene ring shows a higher reactivity than the aromatic nucleus of the benzoxazolinone; the contrary is observed when the benzene ring is p-chloro-substituted.     

A novel synthesis of α,β-unsaturated phosphonates

A stereoselective synthesis of α,β-unsaturated phosphonates based on the reaction of S-(β-oxoalkyl)-dithiophosphates and Se-(β-oxoalkyl)selenophosphates with sodium dialkyl phosphites is described.