Synthesis of 1,4-Diazepanes and Benzo[][1,4]diazepines by a Domino Process Involving the Generation of an Aza-Nazarov Reagent.

A step- and atom-economical protocol allowing the synthesis of 1,4-diazepanes and also tetrahydro- and decahydro-1,5-benzodiazepines is described. The method proceeds from very simple starting materials such as 1,2-diamines and alkyl 3-oxohex-5-enoates and can be performed under solvent-free conditions in many instances. The key event of this process was the generation of an aza-Nazarov reagent and its subsequent intramolecular aza-Michael cyclization.

Fully diastereoselective synthesis of polysubstituted, functionalized piperidines and decahydroquinolines based on multicomponent reactions catalyzed by cerium(IV) ammonium nitrate.

The cerium(IV) ammonium nitrate (CAN)-catalyzed, three-component reaction between primary amines, β-dicarbonyl compounds, and α,β-unsaturated aldehydes in ethanol heated to reflux, constitutes a general, one-pot synthesis of 1,4-dihydropyridines. Their reduction with sodium triacetoxyborohydride furnished piperidine derivatives bearing up to five substituents with full diastereoselectivity in a hitherto inaccessible stereochemical arrangement. The reaction proceeded with no significant loss of enantiomeric purity under mild reduction conditions that are compatible with several functional groups that are normally sensitive to reduction.

Brief, efficient and highly diastereoselective synthesis of (±)-pumiliotoxin C based on the generation of an octahydroquinoline precursor via a four-component reaction.

A short and highly diastereoselective synthesis of the amphibian alkaloid pumiliotoxin C is described, based on the preparation of an octahydroquinoline derivative through a four-component reaction. The route proceeds in 66% overall yield from 1,3-cyclohexanedione and includes two hydrogenation steps, whose stereochemical outcome was controlled via nitrogen acylation.

Synthesis of benzo- and naphtho-fused bicyclo[n.3.1]alkane frameworks with a bridgehead nitrogen function by palladium-catalyzed intramolecular α'-arylation of α-nitroketones.

The C-alkylation of cyclic α-nitroketones with α-halobenzyl halides in the presence of DBU followed by a Pd-catalyzed intramolecular C-arylation afforded benzo-and naphtho-fused bicyclo[n.3.1]alkane derivatives (n = 3, 4, 5) in excellent overall yields for the two-step sequence.

Synthesis of a library of 5,6-unsubstituted 1,4-dihydropyridines based on a one-pot 4CR/elimination process and their application to the generation of structurally diverse fused nitrogen heterocycles.

Indium trichloride is an efficient catalyst for the sequential four-component reaction between aliphatic amines, β-ketoesters, α,β-unsaturated aldehydes, and ethanol to afford 6-ethoxy-1,4,5,6-tetrahydropyridines, which were converted in situ into 5,6-unsubstituted 1,4-dihydropyridines via ethanol elimination in the presence of neutral Al(2)O(3), in a very efficient, one-pot protocol from acyclic, readily available starting materials that involves the generation of two C-N σ and one C-C π bonds. The structural variety of the dihydropyridine library thus generated was extended by base-promoted γ-alkylation of their C-2 position. The application of these 1,4-dihydropyridines to the facile generation of molecular diversity and complexity was demonstrated by employing them as dienophiles for Yb(OTf)(3)-catalyzed imino Diels-Alder (Povarov) reactions leading diastereoselectively to hexahydrobenzo[h][1,6]-naphthyridine derivatives containing three adjacent stereocenters.

Efficient generation of highly functionalized fused oxazepine frameworks based on a CAN-catalyzed four-component tetrahydropyridine synthesis/ring-closing metathesis sequence.

1-Allyl(propargyl)-6-allyl(propargyl)oxy-1,4,5,6-tetrahydropyridines, obtained through a CAN-catalyzed four-component reaction, were transformed into highly functionalized pyrido[2,1-b][1,3]oxazepines by ring-closing metathesis (RCM) and ring-closing enyne metathesis (RCEYM) processes, which constitute the first examples of the preparation of 1,3-oxazepine systems using metathesis reactions.

A very efficient cerium(IV) ammonium nitrate catalyzed, four-component synthesis of tetrahydropyridines and its application in the concise generation of functionalized homoquinolizine frameworks.

Molecular diversity: A cerium(IV) ammonium nitrate (CAN) catalyzed, four-component reaction from very simple acyclic starting materials afforded densely substituted tetrahydropyridines, which were transformed into homoquinolizines by using a gamma-alkylation-ring-closing metathesis (RCM) sequence (see scheme).The cerium(IV) ammonium nitrate (CAN) catalyzed, four-component reaction between primary aliphatic amines, beta-ketoesters or beta-ketothioesters, alpha,beta-unsaturated aldehydes, and alcohols provided a very efficient and atom-economical access to substituted 6-alkoxy-2-methyl-1,4,5,6-tetrahydropyridines. These materials were then transformed into homoquinolizine derivatives in excellent yields by using a two-step sequence comprised of regioselective gamma-deprotonation-allylation and ring-closing metathesis reactions.