A unified approach to sesquiterpenes sharing trimethyl(p-tolyl) cyclopentanes: Formal total synthesis of (±)-laurokamurene B

A unified approach to the sesquiterpenoids sharing common trimethyl(p-tolyl) cyclopentane skeleton has been disclosed via a key Stork-Danheiser sequence on a cyclopentane based vinylogous ester with aryl Grignard reagent followed by α-methylation strategy. The strategy is eventually applied to the concise formal total synthesis of (±)-laurokamurene B (1b) in only 5 steps with 45.4% overall yield.     

Generation of medium-ring cycloalkynes by ring expansion of vinylogous acyl triflates

Reductive cyclization of aryl and vinyl iodides tethered to vinylogous acyl triflates (VATs) induces a ring-expanding fragmentation to provide cyclic alkynyl ketones, including strained nine-membered cycloalkynes, in fair to excellent yield. The tandem cyclization/C-C bond-cleavage is initiated under carefully optimized conditions by halogen-metal exchange in the presence of carbonyl and vinyl triflate functionality. A modified protocol for alkylation of 1,3-cyclohexanedione is described for preparing the relevant VAT substrates.     

Equilibrium between a vinylogous ylide and a phosphonium dienolate zwitterion: vinylogous Wittig olefination versus vinylogous aldol-type reaction

This paper describes the equilibrium established between a phosphonium dienolate zwitterion and a vinylogous phosphorus ylide, and their reactions with aldehydes. The reactions between ethyl 2-methyl-2,3-butadienoate and various aldehydes occur through either a phosphonium dienolate or a vinylogous ylide intermediate, depending on the presence/absence of a Lewis acid and the nature of the phosphine. We observed a rare vinylogous Wittig olefination from the reaction between ethyl 2-methyl-2,3-butadienoate and an electron-deficient aromatic aldehyde in the presence of a stoichiometric amount of an electron-deficient triarylphosphine and a catalytic amount of a Lewis acid (e.g., BF₃·Et₂O). On the other hand, the use of triphenylphosphine, in the absence of a Lewis acid, facilitated vinylogous aldol addition, accompanied by a rare 1,2-aryl phosphorus-to-carbon migration.     

Triflic Salt–Catalyzed Coupling: Iron Triflate–Catalyzed Homocoupling of Aryl Bromides in the Presence of Metallic Magnesium

In the presence of metallic magnesium, the homocoupling reaction of aryl bromides catalyzed by iron triflate was carried out readily in one pot. The catalyst was used successfully in this coupling reaction without preparation of Grignard reagent in advance. Meanwhile, the catalyst was recovered easily and reused smoothly with only a little loss of its activity.     

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.     

Tandem nucleophilic addition/fragmentation reactions and synthetic versatility of vinylogous acyl triflates

A thorough analysis of the chemistry of vinylogous acyl triflates provides insight into important chemical processes and opens new directions in synthetic technology. Tandem nucleophilic addition/C-C bond cleaving fragmentation reactions of cyclic vinylogous acyl triflates 1 yield a variety of acyclic acetylenic compounds. Full details are disclosed herein. A wide array of nucleophiles, such as organolithium and Grignard reagents, lithium enolates and their analogues, hydride reagents, and lithium amides, are applied. The respective reactions produce ketones 2, 1,3-diketones and their analogues 3, alcohols 4, and amides 5. The present reactions are proposed to proceed through a 1,2-addition of the nucleophile to the carbonyl group of starting triflates 1 to form tetrahedral alkoxide intermediates C, followed by Grob-type fragmentation, which effects C-C bond cleavage to yield acyclic acetylenic compounds 2-5 and 7. The potent nucleofugacity of the triflate moiety is channeled through the sigma-bond framework of 1, providing direct access to the fragmentation pathway without denying other typical reactions of cyclic vinylogous esters. The synthetic versatility of vinylogous acyl triflates, including functionalization reactions of the cyclic enone core (1 --> 6 or 8), is also illustrated.     

Synthesis and properties of 1-methylthiopropargylammonium salts and their use as key precursors to sulfur-containing enediynes

1-methylthiopropargylammonium salts were synthesized in a highly efficient manner by reaction of alkynyl S,N-acetals with methyl triflate. Reactions of the 1-methylthiopropargylammonium salts with Grignard reagents gave propargyl sulfides or allenyl sulfides, whereas the reaction with organocopper reagents led to exclusive formation of allenyl sulfides regardless of the nature of substituents on the acetylenic carbon. The salts undergo self-dimerization reactions when treated with organolithium and lithium amide bases.     

On the chemistry of pyrrole pigments,LXXXIX: Vinylogous linear di- and tetrapyrroles

Summary A vinylogous dipyrrinone, its Ehrlich aldehyde condensate, and the vinylogous bilindione derived from the vinylogous dipyrrinone were prepared. Their structural aspects of tautomerism, configuration and conformation were derived by analysis of their¹H-NMR data. Selected physical properties were determined and are discussed.

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Zur Chemie von Pyrrolpigmenten, 89. Mitt.: Vinyloge Lineare Di- und Tetrapyrrole

Zusammenfassung Ein vinyloges Dipyrrinon, sein Ehrlich-Aldehyd-Kondensat und ein vom vinylogen Dipyrrin abgeleitetes vinyloges Bilindion wurden dargestellt. Ihre strukturellen Aspekte der Tautomerie, Konfiguration und Konformation wurden durch Analyse ihrer¹H-NMR-Daten abgeleitet. Ausgewählte physikalische Eigenschaften wurden gemessen und diskutiert.

     

AgOTf‐Catalyzed Electrophilic Cyclization of Triynols with NXS: Rapid Synthesis of Densely Trisubstituted Naphthalenes and Quinolines

A silver triflate‐catalyzed electrophilic cyclization reaction of acyclic triynols with NXS (X=I, Br) under mild conditions is reported. Three reactive functional groups, such as a carbonyl group, an alkyne group, and a halogen, could be selectively installed at the C1, C2, and C3 positions to obtain the naphthalene and quinoline products, respectively. The obtained densely trisubstituted products could be further transformed into more complex aromatic products by manipulating the alkynyl moiety and the other two functional groups as synthons.     

Efficient and practical catalytic vinylogous aldol reaction of dioxinone-derived silyl dienol ethers with aromatic aldehydes

Vinylogous Mukaiyama-aldol reaction was realized by use of dioxinone-derived silyl dienol ethers and various aldehydes in the presence of highly catalytic amounts of bismuth triflate. The reaction proceeds rapidly and affords the corresponding β-hydroxy-1,3-dioxin-4-ones in very good to excellent yields (up to 98%).     

An efficient synthesis of vinylogous carbamates from alkyl azides

An efficient one-pot synthesis of vinylogous carbamates is reported starting from alkyl azides by using NH₄Cl/Zn dust.     

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.     

Recent progress on direct catalytic asymmetric vinylogous reactions

Direct catalytic asymmetric vinylogous reaction serves as a powerful tool to introduce stereocenter(s) at the γ- or/and even more remote position(s) of the vinylogous products in an atom-economical and efficient way. A variety of direct catalytic asymmetric vinylogous reactions with broad substrate scope and mild reaction conditions has been developed. Both metal catalysis and organocatalysis contributed in this field and led to the vinylogous products in high stereoselectivity. These vinylogous reactions provided efficient pathways for the synthesis of highly functionalized optically pure compounds, especially these with potential biological activity and pharmacological activity. This digest paper mainly focuses on the most recent developments in this field, including both nucleophilic addition and nucleophilic substitution.     

Further studies on the application of vinylogous amides and β-halovinylaldehydes to the regiospecific synthesis of unsymmetrical,polyfunctionalized 2,3,4- and 1,2,3,4- substituted pyrroles

Highly functionalized pyrroles with appropriate regiochemical functionality represent an important class of marine natural products and potential drug candidates. We describe herein a detailed study of the reaction of α-aminoacid esters with vinylogous amides and also β-halovinylaldehydes for the regiospecific synthesis of 2,3,4-trisubstituted and 1,2,3,4-tetrasubstituted pyrroles. Since the vinylogous amides and β-halovinylaldehydes are readily available precursors, rapid access to a wide variety of unsymmetrically substituted pyrroles is accomplished via this methodology.     

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.     

Hg(OTf)2-Catalyzed cyclization of alkynyl tert-butylcarbonate leading to cyclic enol carbonate

Mercuric triflate was shown to be a powerful catalyst for the cyclization of alkynyl tert-butylcarbonates giving rise to cyclic enol carbonates under mild conditions. Internal alkynyl carbonate affords endo cyclization product selectively, while terminal alkynyl carbonate provides only exo cyclization product.     

Y(OTf)3 catalyzed substitution dependent oxidative C(sp)–C(sp) cleavage and regioselective dehydration of β-allyl-β-hydroxydithioesters: alternate route to α,β-unsaturated ketones and functionalized dienes

β-Allyl-β-hydroxydithioesters have been generated by the regioselective Grignard addition to the β-oxodithioesters. They have been successfully employed in selective C(sp³)–C(sp³) bond cleavage to construct α,β-unsaturated ketone residues by the treatment of an emerging catalyst yttrium(III)triflate for the first time. On the other hand, hetaryl substituted β-allyl-β-hydroxydithioesters led to the useful diene precursors through selective dehydration under the similar conditions.     

Efficient synthesis of highly functionalized vinylogous thiol esters

A series of vinylogous thiol esters 2,3 and 2,6-dioxo-1,2,5,6-tetrahydropyridines (cyclic vinylogous thiol esters) 4 were prepared in high to excellent yields from the tandem reaction of readily available α-alkenoylketene diethylthioacetals 1 and diethyl malonate. A plausible mechanism, which involves a base catalyzed retro-Michael ring opening of cyclohexanenes 2 to give vinylogous thiol ester 3, is disclosed.     

DMAP catalysed vinylogous Rauhut–Currier reaction of allenoates with para-quinone methides

The hitherto unknown, organocatalysed (DMAP) vinylogous Rauhut-Currier reaction of 2,3-butadienoates with para-quinone methides has been achieved. The products, diarylmethane substituted allenoates, are formed in high to excellent yields under mild reaction conditions.