Selective functionalizations of 2-phenylpyridine: lactones upon organic versus organometallic activations

2-Phenylpyridine activated by chromium tricarbonyl reacts with bis(TMS) ketene acetals to give pyridine-substituted bicyclic γ-lactones. On the other hand, its reaction with the same acetals leads, upon activation with methylchloroformate, to dihydropyridines which can be oxidized to highly substituted, lactone-containing piperidines.     

Co-catalyzed reductive cyclization of azido and cyano substituted α,β-unsaturated esters with NaBH4: enantioselective synthesis of (R)-baclofen and (R)-rolipram

Sodium borohydride in combination with a catalytic amount of CoCl₂ has been found to be an excellent catalytic system in reductive cyclizations of suitably substituted azido and cyano groups of α,β-unsaturated esters to afford γ and δ-lactams in high yields. The process has been demonstrated for the enantioselective synthesis of (R)-baclofen, (R)-rolipram, and (R)-4-fluorophenylpiperidinone, a key intermediate for (−)-paroxetine.     

Synthesis and thermal decomposition of 3-aroyl-4-aryl-2-pyrazolines

Summary 3-Aroyl-4-aryl-2-pyrazolines (21–40) have been synthesized by the reaction of ,-unsaturated ketones (1–20) with diazomethane. These 2-pyrazolines gave -methyl-,-unsaturated ketones (41–46) on thermal denitrogenation.Dedicated to Prof. Dr.F. Sauter on the occasion of his 65^th birthday     

Synthesis of podophyllotoxin analogues: δ-lactone-containing picropodophyllin, podophyllotoxin and 4′-demethyl-epipodophyllotoxin derivatives

Non-epimerizable cis and trans δ-lactone analogues of podophyllotoxin have been prepared. Thus the synthesis of the cis isomer 4 has been achieved in 8 steps and 4% overall yield from podophyllotoxin 1 via the reduction of the γ lactone ring into the trans diol, selective protection of the 4-OH and 11-OH as a benzylidene acetal, and Wittig elongation at C-13 with inversion of configuration at C-2. Same elongation at C-13 but via the formation of a mesylate and introduction of a cyano group, led to the trans δ-lactone 5 (7 steps from 1 and 6% overall yied) with a small amount of its C-4 epimer 6. The synthesis of non-epimerizable δ-lactone analogues of 4′-demethyl-epipodophyllotoxin 7 and of 4-demethyl podophyllotoxin 8 are also reported. The synthesis of 7 and 8 was based upon the reduction of the γ-lactone ring of 4′-demethyl-4-epipodophyllotoxin followed by selective protection at C-11 and elongation at C-13. (8-15% and 4% overall yields). Compounds 4, 5 and 7 did not display relevant cytotoxicity in vitro against L1210 murine leukemia.     

A convenient synthesis of enantiopure (4aS,7aR)-1,4,4a,7a-tetrahydrocyclopenta[c]pyran-3,7-dione

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Nitrosation of β′-hydroxylamino-α,β-unsaturated oximes: synthesis of 1,7-dioxa-2,6-diaza-spiro[4,4]nona-2,8-diene ring system

Nitrosation of bis arylidene acetone oximes with nitrous acid in glacial acetic acid gives 3-vinyl pyrazolone-N,N′-dioxides in 32-37% yield. Similar reactions of 2-arylidene-6-(hydroxylamino-aryl-methyl)-cyclohexanone oximes give tricyclic compounds with dioxa-2,6-diaza-spiro[4,4]nona-2,8-diene ring systems in 77-84% yield.     

Microwave-promoted one-pot synthesis of 4H-thiopyrans from α,β-unsaturated ketones via a three-component reaction

An efficient one-pot synthesis of substituted 4H-thiopyrans has been accomplished from a three-component reaction of α,β-unsaturated ketones, Lawesson’s reagent and alkynes under microwave irradiation.     

One-step synthesis ofα,β-unsaturated arylsulfones by a novel multicomponent reaction of aromatic aldehydes,chloroacetonitrile, benzenesulfinic acid sodium salt

A new and green method for the synthesis of α,β-unsaturated arylsulfones had been achieved through the condensation of aromatic aldehydes,chloroacetonitrile,benzenesulfinic acid sodium salt in the presence of l-butyl-3-methyl imidazolium hydroxide([bmim]OH) in EtOH under reflux.The ionic liquid was recovered and recycled for subsequent reactions.The advantages of this protocol were non-toxic,easy work-up and good yields.     

Chemoselective hydrogenation of α,β-unsaturated aldehydes with modified Pd/C catalyst

Selective hydrogenation of α, β-unsaturated aldehydes with modified Pd/C catalyst was developed.The reduction of C=O bond could be efficiently inhibited by the addition of carbonates,and high selectivity to the corresponding saturated aldehydes was achieved under mild conditions.This protocol provides an alternative for efficient preparation of saturated aldehydes.     

The Reaction of 1-Nitro-4-(4-nitrophenylsulfonylmethyl)benzene with α,β-Unsaturated Esters

Under solid-liquid PTC conditions, treatment of 1-nitro-4-(4-nitrophenylsulfonyl-methyl)benzene(1) with α,β -unsaturated esters (2a-h) at 35–75°C gave tandem addition-rearrangement products(3a-h). While at higher temperature(75°C), addition-rearrangement-addition products (4a-b) were obtained when acrylates were used. Finally a possible mechanism is proposed.