A cyclobutene bridgehead olefin approach to the germacranes

A model study for the synthesis of the germacranes is described which utilizes a consecutive oxy-Cope/cyclobutene ring opening rearrangement sequence. The β,γ-unsaturated enone necessary for the rearrangement is obtained directly from the photocycloaddition of allene and cyclohexenone.     

The steering pathway: Ketene-Claisen rearrangement (KCR)-1978–2016

From what began as a casual discovery of the ketene-Claisen rearrangement (the Malherbe-Bellu? rearrangement) over 3 decades ago has flourished a reaction of substantial significance. The noticeable qualities of the ketene-Claisen rearrangement is accomplished in terms of experimental simplicity, forming new CC bonds, high levels of chemo- and stereocontrol, ring enlargements and constructing new stereocenters. This survey of the ketene-Claisen rearrangement with some applications in organic synthesis will not only recapitulate the prospective of this reaction so far but also illustrate the achievable future significant prospective.     

Convergent synthesis of mosloflavone, negletein and baicalein from crysin

An expeditious synthesis of three polyoxygenated flavones: mosloflavone, negletein and baicalein, starting from crysin, an easily available flavone, by a bromination/methoxylation procedure is reported. The convergent synthesis exploits a base induced Wesley-Moser type rearrangement.     

Enantioselective Synthesis of Protease Inhibitors and AntiHIV Agents

Part 1: A highly enantio-and diastereoselective Ireland-Claisen rearrangement of chiral C3(acyloxy)-vinyl silanes for the synthesis of anti-disubstituted succinic acid, an important intermediate for matrix metalloprotease inhibitors, has been developed (enantio-and anti/syn selectivities up to 95% and 38/1). The diastereoselectivity of this reaction was found to be sensitive to remote hydroxyl protecting groups, for example, with-OMOM group, the anti/syn ratio was 19/1, while with-OTBDMS, the ratio was 38/1. The resultant Ireland-Claisen rearrangement product was applied to the synthesis of macrocyclic MMP inhibitors, such as SL 422.     

Stereoselective synthesis of (−)-ara-cyclohexenyl-adenine

A stereoselective synthesis leading to (−)-ara-cyclohexenyl-adenine is described. The synthesis starts from methyl-α-d-glucopyranose and involves an isomerization step, selective protection/deprotection chemistry, a Ferrier rearrangement and a Mitsunobu reaction. This is the first total synthesis of an enantiomeric pure ara-type cyclohexenyl nucleoside.     

An Efficient Synthesis of de novo Imidates via Aza-Claisen Rearrangements of N-Allyl Ynamides

A novel thermal 3-aza-Claisen rearrangement of N-allyl ynamides for the synthesis of α-allyl imidates is described. Also, a sequential aza-Claisen, Pd-catalyzed Overman rearrangement is described for the synthesis of azapine-2-ones.     

Stereoselective Total Synthesis of Eburnane‐Type Alkaloids Enabled by Conformation‐Directed Cyclization and Rearrangement

Controlling the cis C20/C21 relative stereochemistry remains an unsolved issue in the synthesis of eburnane‐type indole alkaloids. Provided herein is a simple solution to this problem by developing a unified and diastereoselective synthesis of four representative members of this class of natural products, namely, eburnamonine, larutensine, terengganensine B, and melokhanine E. The synthesis features the following key steps: a) an α‐iminol rearrangement transforming the 3‐hydroxyindolenine into spiroindolin‐3‐one, b) a highly diastereoselective conformation‐directed cyclization leading to the melokhanine skeleton with the desired C20/C21 cis stereochemistry, and c) either an aza‐pinacol or an unprecedented α‐aminoketone rearrangement converting spiroindolinone back into the indole skeleton.     

A general synthetic entry to the pentacyclic strychnos alkaloid family, using a [4 + 2]-cycloaddition/rearrangement cascade sequence

The total synthesis of (+/-)-strychnopivotine, (+/-)-tubifolidine, (+/-)-strychnine, and (+/-)-valparicine is reported. The central step in the synthesis consists of an intramolecular [4 + 2]-cycloaddition/rearrangement cascade of an indolyl-substituted amidofuran that delivers an aza-tetracyclic substructure containing the ABCE-rings of the Strychnos alkaloid family. A large substituent group on the amide nitrogen atom causes the reactive s- trans conformation of the amidofuran to be more highly populated, thereby facilitating the Diels-Alder cycloaddition. The reaction also requires the presence of an electron-withdrawing substituent on the indole nitrogen for the cycloaddition to proceed. The cycloaddition/rearrangement cascade was remarkably efficient given that two heteroaromatic systems are compromised in the reaction. Closure to the remaining D-ring of the Strychnos skeleton was carried out from the aza-tetracyclic intermediate by an intramolecular palladium-catalyzed enolate-driven cross-coupling between the N-tethered vinyl iodide and the keto functionality. The cycloaddition/rearrangement approach was successfully applied to (+/-)-strychnopivotine (2), the only Strychnos alkaloid bearing a 2-acylindoline moiety in its pentacyclic framework. A variation of this tactic was then utilized for a synthesis of the heptacyclic framework of (+/-)-strychnine. The total synthesis of (+/-)-strychnine required only 13 steps from furanyl indole 18 and proceeded in an overall yield of 4.4%.     

Assembling the prenylneoflavone system through a Pechmann condensation/Mitsunobu reaction/Claisen rearrangement/olefin cross-metathesis sequence

Monatshefte für Chemie - Chemical Monthly - The multistep synthesis of a prenylneoflavone through a sequence of the Mitsunobu reaction/Claisen rearrangement/olefin cross-metathesis reaction...     

Alkyne migration in alkylidene carbenoid species: a new method of polyyne synthesis

The synthesis of conjugated polyyne structures via a modification of the Fritsch-Buttenberg-Wiechell (FBW) rearrangement is reported. Our adaptation provides for the 1,2-migration of an alkyne in a carbene/carbenoid intermediate that is conveniently effected via lithium-halogen exchange with the appropriate dibromo-olefinic precursor. This rearrangement is quite rapidly accomplished under mild conditions (hexane solution, -78 degrees C), and the seemingly high migratory aptitude of the alkynyl moiety provides for efficient rearrangement. This, in turn, allows for multiple rearrangements in a single molecule, greatly facilitating the construction of highly unsaturated substrates. This procedure is exploited for the rapid synthesis of symmetrical and unsymmetrical 1,3,5-hexatriynes, extended polyynes, and aryl polyyne building blocks. Most significantly, many of these structures have been or would be difficult to access via more traditional transition metal catalyzed homo- or cross-coupling techniques.     

Concise, Biomimetic Total Synthesis of d,l-Marcfortine C

A biomimetic total synthesis of the fungal metabolite marcfortine C utilizing an intramolecular Diels-Alder reaction is described. In addition, a key stereoselective oxaziridine-mediated oxidation/pinacol rearrangement of indole 24 was used to complete the total synthesis.     

Formal synthesis of (+/-)-dendrobine: use of the amidofuran cycloaddition/rearrangement sequence

The formal synthesis of the alkaloid (+/-)-dendrobine (4) was accomplished using the IMDAF cycloaddition/rearrangement sequence of a furanyl carbamate. Conversion of the rearranged cycloadduct to Kende's advanced intermediate in eight steps completed the formal synthesis of (+/-)-dendrobine.     

Concise formal synthesis of the bryostatin southern hemisphere (C17-C27)

An efficient synthesis of Hale and co-workers' C17-C27 bryostatin southern hemisphere intermediate has been accomplished in six steps and 33% overall yield from (R)-2-(benzyloxy)propanal. The synthesis features a one-pot DIBALH/HWE ester homologation as well as a novel acetonide rearrangement/glycal formation cascade.     

A new strategy toward the total synthesis of stachyflin,a potent anti-influenza A virus agent: concise route to the tetracyclic core structure

[reaction: see text] A new strategy directed toward the total synthesis of stachyflin, a potent and novel anti-influenza A virus agent isolated from a microorganism, has been presented through the enantioselective synthesis of the tetracyclic core structure. The synthetic method features a BF(3) x Et(2)O-induced domino epoxide-opening/rearrangement/cyclization reaction as the key step.     

Combined C-H activation/cope rearrangement as a strategic reaction in organic synthesis: total synthesis of (-)-colombiasin a and (-)-elisapterosin B

The total synthesis of (-)-colombiasin A (2) and (-)-elisapterosin B (3) has been achieved. The key step is a C-H functionalization process, the combined C-H activation/Cope rearrangement, between methyl (E)-2-diazo-3-pentenoate and 1-methyl-1,2-dihydronaphthalenes. When the reaction is catalyzed by dirhodium tetrakis((R)-(N-dodecylbenzenesulfonyl)prolinate), Rh(2)(R-DOSP)(4), an enantiomer differentiation step occurs where one enantiomer of the dihydronaphthalene undergoes the combined C-H activation/Cope rearrangement while the other undergoes cyclopropanation. This sequence controls the three key stereocenters in the natural products such that the remainder of the synthesis is feasible using standard chemistry.     

Novel oxidative nitrogen to carbon rearrangement found in the conversion of anilines to benzaldoximes by treating with HCHO/H2O2

Novel rearrangement was found by reacting anilines with HCHO/H₂O₂ resulting in the synthesis of various benzaldoximes. The mechanism of the rearrangement is proposed and suggested that the rearrangement might proceed via unstable N-phenyloxazirane intermediate followed by the transfer of aryl moiety from nitrogen to carbon atom leading to the formation of benzaldoxime.     

A new synthetic route to nucleosides: dissymmetric construction of a cyclopentene system by double [3,3]-sigmatropic rearrangement and double ring-closing metathesis

[reaction: see text] The dissymmetric synthesis of a carbocyclic nucleoside was achieved by a novel double [3,3]-sigmatropic rearrangement/double ring-closing metathesis strategy with a high stereoselectivity.     

A transition metal-free tandem process to pyrrolopyrazino[2,3-d]pyridazine-diones

A transition metal-free tandem process for the synthesis of pyrrolopyrazino[2,3-d]pyridazine-diones is described. The process is an efficient construction of this tricyclic system by a one-pot coupling/Smiles rearrangement/cyclization approach. This methodology has potential applications in the synthesis of biologically and medicinally relevant compounds.     

Total synthesis of (3S,4S,2′S)- and (3R,4R,2′S)-viridiofungin A triester

The total synthesis of an alkylcitrate secondary metabolite from the fungi Trichoderma viride is described. An ester dienolate [2,3]-Wittig rearrangement and a S. Julia-Kocienski olefination served as key C/C-connecting transformations. The highly convergent synthesis consists of a longest linear sequence of 17 steps.     

Enantioselective formal total synthesis of aplysin utilizing a palladium-catalyzed addition of an arylboronic acid to an allenic alcohol—Eschenmoser/Claisen rearrangement

The enantioselective formal total synthesis of aplysin has been achieved utilizing a palladium-catalyzed addition of arylboronic acid to the allenic alcohol followed by the Eschenmoser/Claisen rearrangement as the key steps.