An effective and highly stereoselective Julia olefination of cyclopropyl carbinol mediated by CeCl3.7H2O/NaI

[reaction: see text] An efficient and highly stereoselective synthesis of functionalized trisubstituted E-olefins from cyclopropyl carbinol derivatives via a Julia-type olefination mediated by an intriguing Lewis acidic system consisting of CeCl(3).7H(2)O and NaI in refluxing acetonitrile is reported. This facile olefination allows for the iterative incorporation of methylcyclopropyl ketone as a C(5) prenylation synthon in the synthesis of acyclic terpenoids, as demonstrated in the facile synthesis of plaunotol 6E-isomer 12, a biologically significant diterpene diol, and naturally occurring diterpene 17.     

Synthesis of Functionalized α‐Vinyl Aldehydes from Enaminones

An efficient Rh^II‐catalyzed synthesis of functionalized α‐vinyl aldehydes with high E/Z stereoselectivity was developed. The reaction mediates the cyclopropanation of enaminones with vinyl carbenoids that are generated from cyclopropenes in situ to give the aminocyclopropane intermediates. Selective C?C bond cleavage of the cyclopropane intermediates leads to formation of α‐vinyl aldehyde derivatives with high E/Z selectivity. This method proceeds at room temperature under very mild reaction conditions and works with a broad substrate scope.     

Synthesis of β‐Substituted γ‐Aminobutyric Acid Derivatives through Enantioselective Photoredox Catalysis

β‐Substituted chiral γ‐aminobutyric acids feature important biological activities and are valuable intermediates for the synthesis of pharmaceuticals. Herein, an efficient catalytic enantioselective approach for the synthesis of β‐substituted γ‐aminobutyric acid derivatives through visible‐light‐induced photocatalyst‐free asymmetric radical conjugate additions is reported. Various β‐substituted γ‐aminobutyric acid analogues, including previously inaccessible derivatives containing fluorinated quaternary stereocenters, were obtained in good yields (42–89 %) and with excellent enantioselectivity (90–97 % ee). Synthetically valuable applications were demonstrated by providing straightforward synthetic access to the pharmaceuticals or related bioactive compounds (S)‐pregabalin, (R)‐baclofen, (R)‐rolipram, and (S)‐nebracetam.     

Efficient transformation of azides to primary amines using the mild and easily accessible CeCl3.7H2O/NaI system

Because of the nitrogen functionality, the azido group plays an important role in the synthesis of amines, and numerous reduction methods of azides to primary amines are reported. Recent reports have highlighted the capability of NaI as a useful reagent for this transformation when it is used in combination with a Lewis acid promoter. However, these methods often suffer from harsh reaction conditions; for this reason, the development of a simple and efficient protocol using NaI in presence of inexpensive and readily available cerium salts Lewis acids would extend the scope of this organic transformation. In continuation of our interest on the use of the CeCl3.7H2O/NaI system, in this paper we report how azides undergo reduction by NaI in the presence of CeCl3.7H2O in refluxing acetonitrile under neutral conditions to produce the corresponding primary amines. The rate and yield of the reaction are considerably improved by employing this microwave-assisted procedure, and this may be of value for the preparation of densely functionalized molecules having biological and pharmaceutical activities.     

Synthesis and Biological Activity of a Series of Novel N‐Substituted β‐Lactams Derived from Natural Gallic Acid

A series of novel β‐lactams derived from natural gallic acid were conveniently synthesized via classical Staudinger ketene‐imine cycloaddition reaction. Their structures were confirmed by satisfactory analytical and spectroscopic methods. The preliminary bioassay showed that some of the target compounds exhibited obvious insecticidal activity against Heliothis armigera at the dosage of 0.2 mg/mL.     

Synthesis of β‐Arylacyl/β‐Heteroarylacyl‐β‐alkylidene Malonates and Their Application in Substituted Pyridone Synthesis

A novel approach has been developed for the synthesis of β‐arylacyl/β‐heteroarylacyl‐β‐alkylidine malonates in moderate to good yields by the reaction of Stork aryl and heteroaryl enamine with β‐chloroalkylidene malonates. The reaction involves conjugate (Michael) addition of Stork enamine on β‐chloroalkylidene malonates and elimination of chloride ion. These Michael adducts were utilized as intermediates for the synthesis of highly substituted 1,4‐dialkyl‐2‐oxo‐6‐aryl/hetreoaryl‐1,2‐dihydro‐pyridine‐3‐carboxylic acid ethyl esters via 5 + 1 ring annulation protocol.     

Synthesis of Novel β‐Lactams from Phenothiazin‐10‐ylacetic Acid

The first synthesis of 3‐phenothiazine‐β‐lactams is herein reported. Thirteen new derivatives of β‐lactams were synthesized using various Schiff bases and (phenothiazin‐10‐yl)acetic acid, which in turn was prepared starting from phenothiazine. The sole product of the Staudinger ketene–imine [2 + 2] cycloaddition reaction is the trans‐β‐lactam. All the synthesized compounds were characterized by elemental analyses and spectral (IR, ¹H‐NMR, and ¹³C‐NMR) data.     

Synthesis of 3‐Aryl/methoxycarbonyl‐3,4‐dihydroisocoumarin‐6‐carboxylic Acid Derivatives

3‐Substituted methyl 3,4‐dihydroisocoumarin‐6‐carboxylates were obtained by the intramolecular cyclization of 2,5‐dimethoxycarbonyl benzenediazonium bromides with methyl/ethyl acrylate and styrenes under Meerwein's arylation conditions.     

A New Route to N‐Aryl 2‐Alkenamides,N‐Allyl N‐Aryl 2‐Alkenamides,and N‐Aryl α,β‐Unsaturated γ‐Lactams from N‐Aryl 3‐(Phenylsulfonyl)propanamides

A series of N‐aryl 2‐alkenamides were produced efficiently by treating N‐aryl 3‐(phenylsulfonyl)‐propanamides with potassium tert‐butoxide in THF at 0°C. With out isolation, it was further treated with an additional equivalent of potassium tert‐butoxide and allyl bromide to give N‐allyl N‐aryl 2‐alkenamides in one pot in good yields. Followed by a ring‐closing metathesis reaction, these N‐allyl N‐aryl 2‐alkenamides were respectively converted into corresponding N‐aryl α,β‐unsaturated γ‐lactams in moderate yields.     

Improved heteroatom nucleophilic addition to electron-poor alkenes promoted by CeCl3.7H2O/NaI system supported on alumina in solvent-free conditions

Conjugate addition of heteroatom nucleophiles to carbon-carbon double bonds conjugated with a strong electron-withdrawing group is one of the most important new bond-forming strategies in synthetic organic chemistry. Among the methods for these Michael additions, Lewis acids have shown the best promoter activity, and in particular, the use of reagents impregnated over inorganic supports is rapidly increased. With the increase of environmental consciousness in chemical research, the solvent-free Michael addition has attracted our attention. In continuation of our ongoing program to develop synthetic protocols utilizing cerium trichloride, we report an extension of the CeCl(3).7H(2)O/NaI combination supported under solvent-free conditions to promote heteroatom Michael addition. Using neutral alumina (Al(2)O(3)) as solid support permits us to circumvent some of the problems associated with the procedure where the inorganic support is silica gel. The CeCl(3).7H(2)O/NaI/Al(2)O(3) system works well for hetero-Michael additions utilizing weakly nucleophiles such as imidazoles and carbamates, and also the reaction proceeds with good yields in the case of Michael acceptors different from alpha,beta-unsaturated carbonyl compounds. An important synthetic application of this our methodology is the intramolecular aza-Michael reaction in producing 4-piperidinone derivatives, which are of interest as synthetic intermediates toward important classes of heterocycles.     

Visible‐Light‐Mediated Synthesis of β‐Chloro Ketones from Aryl Cyclopropanes

We report the visible‐light‐mediated synthesis of β‐chloro ketones from aryl cyclopropanes, oxygen, hydrochloric acid, and nitric acid. The operationally simple and catalyst‐free method uses cheap standard laboratory reagents and displays broad functional‐group tolerance. Moreover, scale up of the reaction and late‐stage functionalization of bioactive compounds is possible, providing the opportunity to utilize the cyclopropane ring as a masked β‐chloro ketone in a reaction sequence. We propose a light‐driven radical chain reaction initiated by the reaction of diluted hydrochloric and nitric acid to produce small quantities of molecular chlorine. The mechanistic hypothesis is supported by ¹⁸O labelling and UV/Vis experiments, cyclovoltammetry, and several control reactions.     

CeCl3/Sm System Induced Reductive Cleavage of the Se‐Se Bond in Diaryl Diselenides: A Novel Method for the Synthesis of β‐Selenoesters and β‐Selenonitriles

The Se‐Se bond in diselenides was reduced by CeCl₃/Sm system to produce selenolate anions, which react with α,β‐unsaturated esters or α,β‐unsaturated nitriles to afford β‐selenoesters and β‐selenonitriles, respectively.