Nickel‐catalyzed oxidative esterification of formamides with 1,3‐dicarbonyl compounds under mild reaction conditions

Synthesis of enol carbamates was achieved via nickel‐catalyzed oxidative coupling of formamides with 1,3‐dicarbonyl compounds in the presence of tert ‐butyl hydroperoxide at 40 °C. Various derivatives of enol carbamates were synthesized by this method in good to excellent yields.     

Synthesis and characterization of new α,β‐unsaturated γ‐lactones: Alkyl 3‐acetyl‐4‐hydroxy‐2‐methyl‐5‐oxo‐2,5‐dihydrofuran‐2‐ylcarbamates

A convenient procedure for the preparation of carbamate derivatives of 5‐oxo‐2,5‐dihydrofuran ( 3 ) was described. The method is based on the Michael type addition of three alkyl carbamates ( 2 ) with 4‐acetyl‐5‐methyl‐2,3‐dihydro‐2,3‐furandione ( 1 ). According to ¹H nmr spectra of compounds show tautomeric forms ( 3,4,5 ) in CDC1₃. In the solid state the synthesized compounds are enol forms ( 3 ). The products were characterized with molecular spectroscopic methods.     

Regio- and stereoselective synthesis of novel (E)-1-alkenyl carbamate via carbocupration reaction

The stereoselective carbocupration and copper-catalyzed carbomagnesiation reactions of alkynyl carbamates are described as a new and straightforward method for the preparation of (E)-alkenyl enol carbamates. [reaction: see text]     

Access to Vinyl Ethers and Ketones with Hypervalent Iodine Reagents as Oxy‐Allyl Cation Synthetic Equivalents

We report an Umpolung strategy of enol ethers to generate oxy‐allyl cation equivalents based on the use of hypervalent iodine reagents. Under mild basic conditions, the addition of nucleophiles to aryloxy‐substituted vinylbenziodoxolone (VBX) reagents, easily available in two steps from silyl alkynes, resulted in the stereoselective formation of substituted aryl enol ethers. The reaction was most efficient with phenols as nucleophiles, but preliminary results were also achieved for C‐ and N‐ nucleophiles. In absence of external nucleophiles, the 2‐iodobenzoate group of the reagent was transferred. The obtained aryl enol ethers could then be transformed into α‐difunctionalized ketones by oxidation. The described “allyl cation”‐like reactivity contrast with the well‐established “vinyl‐cation” behavior of alkenyl iodonium salts.     

Base‐Promoted Coupling of Carbon Dioxide,Amines, and Diaryliodonium Salts: A Phosgene‐ and Metal‐Free Route to O‐Aryl Carbamates

A phosgene‐ and metal‐free synthesis of O‐aryl carbamates is realized through a three‐component coupling of carbon dioxide, amines and diaryliodonium salts. The reaction only requires a base as the promoter, providing access to a diverse array of O‐aryl carbamates in moderate to high yields with excellent chemoselectivity.     

Highly Stereoselective Gold‐Catalyzed Coupling of Diazo Reagents and Fluorinated Enol Silyl Ethers to Tetrasubstituted Alkenes

We report a highly stereoselective synthesis of all‐carbon or fluorinated tetrasubstituted alkenes from diazo reagents and fluorinated enol silyl ethers, using C−F bond as a synthetic handle. Cationic Au^I catalysis plays a key role in this reaction. Remarkable fluorine effects on the reactivity and selectivity was also observed.     

Regio‐ and Stereoselective Synthesis of Fully Substituted Silyl Enol Ethers of Ketones and Aldehydes in Acyclic Systems

The regio‐ and stereoselective preparation of fully substituted and stereodefined silyl enol ethers of ketones and aldehydes through an allyl‐Brook rearrangement is reported. This fast and efficient method proceeds from a mixture of E and Z isomers of easily accessible starting materials.     

Bio‐Inspired Formal Synthesis of Hirsutellones A–C Featuring an Electrophilic Cyclization Triggered by Remote Lewis Acid‐Activation

A bio‐inspired strategy was used to complete the formal synthesis of the antitubercular hirsutellone B and congeners A and C, through construction of its decahydrofluorene core from a linear polyene strand activated at both ends by a silyl enol ether and an allyl acetate. Our synthesis features a key electrophilic cyclization, starting with the remote activation (by [Yb(OTf)₃] or BF₃ ? OEt₂) of the allyl acetate and stereoselectively affording the C ring. This was followed by an intramolecular Diels–Alder reaction to get the tricyclic core of the natural product. The stereoselective reduction of the resulting ketone towards the formal intermediate was critical to the success of this strategy.     

Preparation of substituted 1,3‐dihydro‐2H‐imidazo[4,5‐c]pyridin‐2‐ones

A new synthetic route to 6‐substituted‐imidazo[4,5‐c]pyridin‐2‐ons from 4‐aminopyridine has been investigated. 4‐Aminopyridine protected as alkyl carbamates were nitrated with dinitrogen pentoxide to the corresponding methyl, i‐propyl and t‐butyl 3‐nitropyridin‐4‐yl carbamates ( 5a‐c ) in 51‐63 % yields. Attempts to substitute these in the 6‐position by the ONSH and the VNS techniques succeeded with butyl‐amine and the t‐butyl carbamate 9 . From the methyl or t‐butyl 3‐nitropyridin‐4‐yl carbamates 5a, 5c 1,3‐dihydro‐2H‐imidazo[4,5‐c]pyridin‐2‐one ( 1 ) was formed in 73 and 39 % yields, respectively. t‐Butyl 6‐N‐butylamin‐3‐aminopyridin‐4‐yl carbamate ( 6 ) gave 6‐butylamino‐1,3‐dihydro‐2H‐imidazo[4,5‐c]‐pyridin‐2‐one (7) in 53 % yield.     

Total Synthesis of (±)‐Corymine

The first total synthesis of the hexacyclic indole alkaloid (±)‐corymine is described. Starting from the readily available N‐protected tryptamine, the title compound was achieved in 21 steps in 3.4 % overall yield. Key steps of the synthesis include: a) the addition of a malonate to a 3‐bromooxindole to afford 3,3‐disubstituted oxindole, b) the formation of a 12‐membered cyclic enol ether by intramolecular O‐propargylation, immediately followed by propargyl Claisen rearrangement to provide the α‐allenyl ketone stereospecifically, c) DMDO oxidation to install a hydroxy group in a highly stereoselective manner, and d) the SmI₂‐mediated reductive C−O bond cleavage to remove the α‐keto carboxyl group.     

Synthesis of the Strychnos Alkaloid (−)‐Strychnopivotine and Confirmation of its Absolute Configuration

The first enantioselective synthesis of (?)‐strychnopivotine from a known and inexpensive phenol has been achieved in 15 steps. The strategy is based on a new diastereoselective aza‐Michael‐enol‐ether cascade desymmetrization of a dienone, guided by a removable lactic acid‐derived chiral auxiliary. Synthesis involves a phenol dearomatization, a conjugated silicon addition, a stereoselective double reductive amination, and two Heck‐type carbopalladations as key steps. The absolute configuration of the natural compound, which, to date, has been uncertain, was confirmed by using circular dichroism (CD) spectroscopy and X‐ray analyses.     

Enantioselective RH-catalyzed hydrogenation of enol acetates and enol carbamates with monodentate phosphoramidites

[reaction: see text] Monodentate phosphoramidites, in particular PipPhos and its octahydro analogue, are excellent ligands for the rhodium-catalyzed asymmetric hydrogenation of aromatic enol acetates, enol carbamates, and 2-dienol carbamates up to 98% ee. These latter substrates were hydrogenated selectively to the carbamates of the allyl alcohol.     

Transition‐Metal‐Free Ring‐Opening Silylation of Indoles and Benzofurans with (Diphenyl‐tert‐butylsilyl)lithium

A practical method is presented for ring opening various indoles and benzofurans with concomitant stereoselective silylation using readily generated (diphenyl‐tert ‐butylsilyl)lithium to afford ortho ‐β‐silylvinylanilines or ‐phenols. Dearomatization of the heteroarene core proceeds in the absence of any transition‐metal catalyst through addition of a silyl anion and a subsequent stereoselective β‐elimination. DFT calculations provide insight into the mechanism. Functionalizing C−X bond cleavage of heteroarenes is rare and generally requires transition‐metal catalysts.     

Applications of Dainshefsky's Dienes in the Asymmetric synthesis of Aza‐Diels‐Alder Reaction

Asymmetric hetero‐Diels‐Alder (AHDA) reactions provide a multitude of opportunities for the highly efficient, regio‐ and stereoselective construction of various heterocycles in enantiomerically pure form. The asymmetric aza‐Diels‐Alder (A‐aza‐DA) reaction using diversely hetero‐dienophiles and hetero‐dienes have been increasingly developed as a valuable method for the synthesis of functionalized nitrogen ring systems. The purpose of this review is to give a detailed discussion of the A‐aza‐DA reaction particularly, the stereoselective reactions of imines as dienophiles with Dainshefsky dienes to obtain optically pure aza‐Diels‐Alder products. The development of stereoselective variants of the reaction make use of imines as the dienophile and Dainshefsky dienes is at the forefront of these studies. This review updates the A‐aza‐DA reactions covering the literature from 1972 till date     

Structure‐Reactivity Relationships as Probes to Acetylcholinesterase Inhibition Mechanisms by Aryl Carbamates. I. Steady‐State Kinetics

From enzyme kinetics, 4‐nitrophenyl‐N‐substituted carbamates 1 are characterized as pseudo‐substrate inhibitors of acetylcholinesterase. However, the activity of the carbamyl enzyme does not recover in the presence of a competitive inhibitor, edrophonium. Therefore, carbamates 1 should be called as the “pseudo‐pseudo‐substrate” inhibitors of the enzyme. Moreover, the ‐logK_i, logk_c, and logk_i values are linearly correlated with Taft‐Ingold equation, log (k/k_o) = ρ*σ* + δ E_s. A three‐step AChE inhibition mechanism by carbamates 1 is proposed. The first step is the pre‐equilibrium protonations of carbamates 1 with ρ* value of ?1.4 from pK_a‐σ*‐correlation. The second step is the enzyme‐carbamates 1 tetrahedral intermediate formation from nucleophilic attack of the active site Ser200 on the protonated carbamates 1 . The ρ* value for the ‐logK_i‐σ*‐E_s‐correlation indicates that the true ρ* value for the second step is 0.5 [= ?0.9 ‐ (‐1.4)]. The δ value of 0.56 for the ‐logK_i‐σ*‐E_s‐correlation indicates that carbamates 1 with bulky substituents retarded the formation of enzyme‐inhibitor tetrahedral intermediates. The third step (k_c step) is the carbamylation step and is the carbamyl enzyme conjugate formation from the enzyme‐carbamates 1 tetrahedral intermediate. The ρ* value of 0.21 for the logk_c‐correlation indicates that the transition state for the carbamylation step is more negative charge than the enzyme‐carbamates 1 tetrahedral intermediate. Moreover, the k_c step is insensitive to substituent effects since there is a cancellation of electronic demands for bond‐making and bond‐breaking components, like S_N2 reactions. The δ value of 0.00 for the logk_c‐correlation indicates that the k_c step is independent of substituent steric effect. Therefore, the product of this step carbamyl enzyme conjugate is as crowded as the enzyme‐carbamates 1 tetrahedral intermediate and is likely bound to the leaving group, p‐nitrophenol.     

A syn‐Selective Aza‐Aldol Reaction of Boron Aza‐Enolates Generated from N‐Sulfonyl‐1,2,3‐Triazoles and 9‐BBN‐H

A syn‐selective aza‐aldol reaction of boron aza‐enolates, generated from N‐sulfonyl‐1,2,3‐triazoles and 9‐BBN‐H, is reported. It provides a sequential one‐pot procedure for the stereoselective construction of 1,3‐amino alcohols, having contiguous stereocenters, starting from terminal alkynes.     

Synthesis of Angularly Substituted trans‐Fused Decalins through a Metallacycle‐Mediated Annulative Cross‐Coupling Cascade

A convergent coupling reaction is described that enables the stereoselective construction of angularly substituted trans‐fused decalins from acyclic precursors. The process builds on our alkoxide‐directed titanium‐mediated alkyne–alkyne coupling and employs a 1,7‐enyne coupling partner. Overall, the reaction is thought to proceed through initial formation of a tetrasusbstituted metallacyclopentadiene, stereoselective intramolecular [4+2] cycloaddition, elimination, isomerization, and regio‐ and stereoselective protonation. Distinct from our early studies directed at the synthesis of trans‐fused hydrindanes, the current annulative coupling reveals an important effect of TMSCl in controlling the final protonation—the event that establishes the stereochemistry of the ring fusion.     

Single‐Crystal X‐ray Diffraction Structure of the Stable Enol Tautomer Polymorph of Barbituric Acid at 224 and 95 K

The thermodynamically stable enol crystal form of barbituric acid, previously prepared as powder by grinding or slurry methods, has been obtained as single crystals by slow cooling from methanol solution. The selection of the enol crystal was facilitated by a density‐gradient method. The structure at 224 and 95 K confirms the enol inferred on the basis of powder data. The enol has bond lengths that are consistent with the expected bond order and with DFT calculations that include treatment of hydrogen bonding. In isolation, the enol is higher in energy than the tri‐keto form by 50 kJ mol^?1 which must be more than compensated by enhanced hydrogen bonding. Both crystal forms have four normal H‐bonds; the enol has two additional H‐bonds with O–O distances of 2.49 Å. Conversion into the enol form occurs spontaneously in the solid state upon prolonged storage of the commercial tri‐keto material. Slurry conversion of tri‐one to enol in ethanol is reversed in direction in ethanol‐D₁.     

Highly Diastereoselective Synthesis of Syn‐1,3‐Dihydroxyketone Motifs from Propargylic Alcohols via Spiroepoxide Intermediates

Syn dihydroxyketone motifs are embedded in a wide range of biologically active natural products, however the development of stereoselective synthetic methods to assemble these structures has proven a challenging task. We report a highly diastereoselective method for the synthesis of syn dihydroxyketones from propargylic alcohols, with wide scope for application in natural product synthesis. The reaction sequence involves regioselective cyclisation of propargylic alcohols with incorporation of a triketone to give enol dioxolanes that are then diastereoselectively epoxidised to form unusual spiroepoxide intermediates. Hydrolysis affords syn dihydroxyketones as essentially single diastereisomers. The reaction sequence is operationally simple, of wide substrate scope, and remarkably can be efficiently carried out as a one‐pot process with no loss of overall yield or diastereoselectivity.     

External‐Photocatalyst‐Free Visible‐Light‐Mediated Synthesis of Indolizines

A visible‐light‐mediated synthesis of valuable polycyclic indolizine heterocycles from easily accessed brominated pyridine and enol carbamate derivatives has been developed. This process, which operates at room temperature under irradiation from readily available light sources, does not require the addition of an external photocatalyst. Instead, an investigation into the reaction mechanism indicates that the indolizine products themselves may be in some way involved in mediating and accelerating their own formation. Preliminary studies also show that these simple heterocyclic compounds may be capable of facilitating other visible‐light‐mediated transformations.