Recent development of vinylogous Mukaiyama aldol reactions

The vinylogous Mukaiyama aldol reaction (VMAR) is a powerful tool of polyketide synthesis, which constructs a large size structure by simultaneous introduction of the stereogenic center(s) and the α,β-unsaturated carbonyl group. A variety of stereocontrolled VMARs have been developed and applied to natural product synthesis. This review is focused on recent development of the vinylogous Mukaiyama aldol reaction using s-trans silyl dienolates.     

Application of vinylogous carbamates and vinylogous aminonitriles to the regiospecific synthesis of uniquely functionalized pyrroles and quinolones

Pyrroles and quinolones represent core structures, which are routinely found in both natural and synthetic bioactive substances. Consequently, the development of efficient and regiospecific methods for the preparation of such heterocycles with unique functionality is of some importance. We describe herein the regiospecific synthesis of 1,2,3,4-tetrasubstituted pyrroles containing polar substituents and such products are prepared from vinylogous carbamates and vinylogous aminonitriles. We also describe the regiospecific synthesis of 3-aryl containing 1,3,6-trisubstituted quinolones from vinylogous carbamates. The use of an amine exchange reaction to prepare precursors for the pyrrole and quinolone forming cyclizations represents a key factor in the strategy.     

Selective functional group transformation using guanidine: the conversion of an ester group into an amide in vinylogous ester-aldehydes of imidazole

An efficient and convenient method has been described for the selective conversion of an ester group into the corresponding carboxamide in vinylogous ester-aldehydes of imidazole. The method uses excess guanidine, which protects the aldehyde function as a diaminodihydro-s-triazine moiety. The carboxaldehyde group is regenerated by hydrolysis of the triazine moiety to provide vinylogous amide-aldehydes of imidazole as the final product.     

A scalable process for the synthesis of (E)-pterostilbene involving aqueous Wittig olefination chemistry

A synthetic approach toward the pharmacologically active (E)-stilbene pterostilbene is described using a Wittig reaction conducted under mildly basic, aqueous conditions. A surprising, non-intuitive difference in (E)/(Z) stereoselectivity was observed comparing the two possible isomeric Wittig routes, allowing for the development of a highly efficient process to access the title stilbene derivative through a one-pot olefination deprotection sequence.     

A highly stereospecific synthesis of (E)-α,β-unsaturated esters

CrCl₂-induced olefination of aldehydes using methyl dichloroacetate exclusively generates (E)-α,β-unsaturated esters in excellent yields. The intermediate α-chloro-β-hydroxy adducts could also be isolated in good yields under conditions of limited reagent.     

A solvent-free amidation of vinylogous esters via direct aziridination

A microwave-mediated aziridination of α,β-unsaturated ketones and esters through the decomposition of ethyl azidoformate has been developed. When the same atom-economical reaction conditions are applied to cyclic vinylogous esters, N-functionalization at the α-position occurs. Based on NMR analysis, these amidation products appear to be formed from the desired aziridine in moderate to good yields.     

Lewis acid-catalyzed Meyer-Schuster reactions: methodology for the olefination of aldehydes and ketones

In principle, the most efficient and atom-economical means of converting an aldehyde or ketone into the homologated α,β-unsaturated ester is through addition/rearrangement sequences involving acetylenic π-bonds (Scheme 1). Implementation of such a strategy for the synthesis of α,β-unsaturated esters is presented: addition of ethoxyacetylene followed by scandium(III) triflate-catalyzed Meyer-Schuster rearrangement reaction. Stereoselectivities range from good to excellent in the formation of disubstituted α,β-unsaturated esters from aldehydes (Table 3). The two-stage olefination of even the most hindered ketones proceeds with near perfect efficiency (Table 4).     

Anodic behaviour of mono- and bisdithiafulvenyl-9,9′-spirobifluorene: insertion of vinylogous TTF into the spirobifluorenyle framework

New three-dimensional copolymers containing 9,9′-spirobifluorenyl-ethylene units were prepared by anodic oxidation of 9,9′-spirobifluorenes 2-mono- or 2,7′-disubstituted by a dithiafulvenyl unit. The synthesis, physicochemical properties and electrochemistry of both monomers and derived oligomers and polymers are reported.     

Alkyl radical cyclization to vinylogous carbonates for the stereoselective synthesis of unsymmetrical dioxa-cage compounds: effect of conformation on the rate of cyclization versus reduction

An efficient strategy for the stereoselective construction of unsymmetrical dioxa-cage compounds containing ether linkages employing a 6-exo-trig alkyl radical cyclization to vinylogous carbonates is developed. The radical precursors are prepared from the diols obtained from the Diels-Alder adducts via iodoetherification followed by addition of the alcohol to the ethyl propiolate. The geometrical constrains play important role in deciding the outcome of the reaction as cyclization versus simple reduction. Formation of the mono-oxa-cage compounds via a 5-exo-trig intramolecular alkyl radical cyclization to olefin is also described. The dioxa-cages could also be assembled employing a tandem oxymercuration reduction-radical cyclization to vinylogous carbonates protocol with equal efficiency and with reduced number of steps.     

anti-Aldol reactions of chiral alcohol-substituted vinylogous urethanes and the synthesis of (−)-prelactone B

This paper describes a convenient and efficient method for synthesizing chiral alcohol-substituted vinylogous urethanes, in which the double bond has E configuration was determined by single crystal X-ray analysis. In addition, we investigated the anti-aldol reactions of these chiral vinylogous urethane anions. The use of (1S,2R,4R)-1-(hydroxydiphenylmethyl)-7,7-dimethylbicyclo[2,2,1]-heptan-2-ol as a chiral auxiliary, provided the best enantioselectivities, and the resulting vinylogous urethane lactone could be used for the synthesis of (−)-prelactone B. A plausible mechanism for the generation of major enantiomeric isomer was discussed.     

A one-step protocol for the chemical derivatisation of glass microfluidic devices

A simple and robust derivatisation system for glass and silica microdevices is described. The device surface is coated in a one-step treatment with a highly cross-linked polystyrene/divinylbenzene/allylsiloxane copolymer. The surface derivatisation is highly resistant to solvents, acids, bases and oxidising or reducing agents.     

A novel one-step method for the reductive allylation of esters and the first total synthesis of (±)-erythrococcamide B

A novel and convenient one-step method for the reductive allylation of aliphatic and alicyclic esters using InBr₃ as a catalyst is reported. This methodology has also been applied in the first total synthesis of (±)-erythrococcamide B.     

An improved cyclization protocol for the synthesis of diazabicyclo[4.3.0]alkanes

We have recently described the synthesis of diazabicyclo[4.X.0]alkanes and their use as ligands for the prostate specific membrane antigene (PSMA). The key step of our synthetic route toward these diazabicycloalkanes is an oxidative cleavage of a bicyclic diol moiety followed by the attack of a nitrogen nucleophile to the resulting intermediate bisaldehyde. We herein describe the mechanism of this ring closure and its stereochemical consequences. In addition, we report a convenient method for trapping intermediate bisaldehydes by Wittig reagents. This trapping allows the synthesis of 3,5-disubstituted proline derivatives, which are shown to be versatile precursors for functionalized diazabicycloalkane dipeptide mimetics.     

A stereoselective approach to 6-alkylated piperidinone & 2-piperidine via three-component vinylogous Mannich reactions (VMR) and a concise synthesis of (S)-anabasine

A three-component diastereoselective vinylogous Mannich-type reaction (VMR) with the silyl ketene acetal (1) was developed. Adducts from the reactions provided valuable intermediates for construction of a variety of chiral 6-alkylated piperidinone and 2-piperidine compounds. The strategy was applied in a concise synthesis (S)-anabasine.     

A simple strategy for the synthesis of optically pure trans-hydrindane systems

A new strategy for the synthesis of optically pure trans-hydrindane systems is reported from an easily available starting material.     

A novel simple and efficient bromination protocol for activated arenes

An efficient, high yielding, and environmentally benign bromination using an alkali metal bromide as the bromine source is disclosed. Investigation of the protocol revealed that the method operates for activated arenes producing the corresponding monobrominated products in good to excellent yields.     

A short route to the macrocyclic core of biaryl ether-based cyclopeptides

A new route based on an intramolecular Horner-Wadsworth-Emmons type olefination of amidophosphonates has been developed for the construction of a 17-membered macrocyclic scaffold related to some biologically important biaryl ether-based cyclic peptides.     

A novel and highly stereoselective route for the synthesis of non-racemic 3-substituted isoindolin-1-one targets

A new, versatile and highly stereoselective approach for the synthesis of non-racemic 3-substituted isoindolin-1-ones is described from a readily available chiral template. The potential of this new protocol is demonstrated through the synthesis of an enantiomerically enriched 3-alkyl N-H isoindolin-1-one target with an e.e. of 98%.