A Three‐Component Enantioselective Cyclization Reaction Catalyzed by an Unnatural Amino Acid Derivative

A new diastereo‐ and enantioselective three‐component cyclization reaction is described. The reaction takes place between a ketone, a carboxylic acid, and a nitroalkene to yield a bicyclic octahydro‐2H‐indol‐2‐one scaffold possessing three chiral centers. This reaction involves a rearrangement of the nitro group under simple thermal conditions. A plausible mechanism is proposed for this new reaction based on DFT calculations and isotope‐labeling experiments. A new concise enantioselective synthesis of the alkaloid (+)‐pancracine is presented as an example of the potential of this novel organocatalytic cyclization reaction in the synthesis of natural products.     

An Upstream By‐product from Ester Activation via NHC‐Catalysis Catalyzes Downstream Sulfonyl Migration Reaction

A sequential reaction combining N‐heterocyclic carbene (NHC) and N‐hydroxyphthalimide (NHPI) catalysis allowed for the upstream by‐product NHPI, which was generated in the NHC‐catalyzed cycloaddition reaction, to act as the catalyst for a downstream nitrogen‐to‐carbon sulfonyl migration reaction. Enantiomeric excess of the major product in the cycloaddition reaction remained intact in the follow‐up sulfonyl migration reaction.     

Diastereoselective Total Synthesis of (±)‐Schindilactone A,Part 3: The Final Phase and Completion

The final phase for the total synthesis of (±)‐schindilactone A ( 1 ) is described herein. Two independent synthetic approaches were developed that featured Pd–thiourea‐catalyzed cascade carbonylative annulation reactions to construct intermediate 3 and a RCM reaction to make intermediate 4 . Other important steps that enabled the completion of the synthesis included: 1) A Ag‐mediated ring‐expansion reaction to form vinyl bromide 17 from dibromocyclopropane 30 ; 2) a Pd‐catalyzed coupling reaction of vinyl bromide 17 with a copper enolate to synthesize ketoester 16 ; 3) a RCM reaction to generate oxabicyclononenol 10 from diene 11 ; 4) a cyclopentenone fragment in substrate 8 was constructed through a Co–thiourea‐catalyzed Pauson–Khand reaction (PKR); 5) a Dieckmann‐type condensation to successfully form the A ring of schindilactone A ( 1 ). The chemistry developed for the total synthesis of schindilactone A ( 1 ) will shed light on the synthesis of other family members of schindilactone A.     

Total Synthesis of (−)‐Nakadomarin A

A highly efficient 12‐step synthesis of the marine alkaloid (?)‐nakadomarin A has been accomplished. The key advanced intermediate, a tetracyclic ketone derivative, was constructed in just seven steps using a sequence that includes an asymmetric Pauson–Khand reaction, an Overman rearrangement reaction, a ring‐closing metathesis reaction, and an amination reaction. Late introduction of the furan ring during the synthesis of (?)‐nakadomarin A means that the key tetracyclic ketone derivative has the potential to serve as an advanced intermediate for the synthesis of related marine alkaloids.     

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     

An Efficient Approach for the Construction of Benzazepine and Benzoxepine Derivatives

A novel and facile synthetic protocol for the construction of benzazepine and benzoxepine derivatives through a copper(I)‐catalyzed reaction of 2‐(2‐ethynylphenyl)‐1‐tosylaziridine or 2‐(2‐ethynylphenyl)oxirane with sulfonyl azides is disclosed. A ketenimine is the key intermediate during the reaction process.     

Convenient,Mild and One‐Pot Synthesis of Double Schiff Bases from Three Component Reaction of Salicylaldehyde,Ammonium Acetate and Aliphatic Aldehydes Accelerated by NEt3 as a Base

A convenient and efficient procedure for one‐pot preparation of double Schiff bases through a three component reaction of salicylaldehyde, ammonium acetate and aliphatic aldehyde was described. In this reaction, N,N′‐bis(salicylidene)‐1,1‐diaminoalkanes was easily obtained in excellent yields and short reaction times under mild reaction condition.     

Efficient Green Procedure for the Synthesis of Coumarin Derivatives by a One‐Pot,Three‐Component Reaction under Solvent‐Free Conditions

A simple, efficient, and general method has been developed for the synthesis of coumarin derivatives through a one‐pot reaction of aromatic aldehydes, 2,2‐dimethyl‐1,3‐dioxane‐4,6‐dione and 5,5‐dimethyl‐1,3‐cyclohexanedione, in the presence of TEBA under solvent‐free conditions using grinding methods. The mild reaction conditions, simple protocol, high yields, and cleaner reaction make this protocol practical and economically attractive.     

Preparation of a Porous polymer by a catalyst‐free diels‐alder reaction and its structural modification by post‐reaction

A microporous polymer is prepared by a catalyst‐free Diels–Alder reaction. A cyclopentadiene with both a diene and a dienophile functionality and a dienophilic maleimide are used for the Diels–Alder reaction. 1,3,5‐Tris(bromomethyl)‐2,4,6‐trimethylbenzene is reacted with sodium cyclopentadienide to produce the multicyclopentadiene‐functionalized monomer. A crosslinked polymer ( CDAP ) is obtained by the reaction of the cyclopentadiene monomer with N,N′‐1,4‐phenylenedimaleimide. The thermal dissociation of the cyclopentadiene dimeric unit and the subsequent Diels–Alder reaction with the maleimide group are investigated by the model reaction. We are able to restructure the crosslinked polymer network by taking advantage of the thermal reversibility of the Diels–Alder linkage. After the post thermal treatment, the BET surface area of the polymer ( CDAP‐T ) is greatly increased from 317 to 1038 m² g^?1. CDAP‐T is functionalized with pyrene by bromination with N‐bromosuccinimide and the subsequent substitution reaction with aminopyrene. The adsorption property of the pyrene‐functionalized polymer for an aromatic dye is investigated using malachite green. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2013, 51, 3646–3653     

Synthesis of α‐Nitro‐α‐diazocarbonyl Derivatives and Their Applications in the Cyclopropanation of Alkenes and in O?H Insertion Reactions

A facile and highly efficient method for the preparation of α‐nitro‐α‐diazocarbonyl derivatives by a diazo‐transfer reaction involving (trifluoromethyl)sulfonyl azide has been developed. These substrates undergo a rhodium‐catalyzed cyclopropanation reaction with a variety of alkenes. A systematic study of the reaction indicated that the diastereoselectivity of the cyclopropanation could be effectively controlled through the modification of the steric bulk of the diazo reagent. A novel O? H insertion reaction of the metal? carbene complex derived from the α‐nitro‐α‐diazocarbonyl reagent afforded the corresponding novel α‐nitro‐α‐alkoxy carbonyl derivatives.     

Flow‐Based Enzymatic Ligation by Sortase A

Sortase‐mediated ligation (sortagging) is a versatile, powerful strategy for protein modification. Because the sortase reaction reaches equilibrium, a large excess of polyglycine nucleophile is often employed to drive the reaction forward and suppress sortase‐mediated side reactions. A flow‐based sortagging platform employing immobilized sortase A within a microreactor was developed that permits efficient sortagging at low nucleophile concentrations. The platform was tested with several reaction partners and used to generate a protein bioconjugate inaccessible by solution‐phase batch sortagging.     

Deaminative (Carbonylative) Alkyl‐Heck‐type Reactions Enabled by Photocatalytic C−N Bond Activation

The palladium‐catalyzed Heck reaction is a well‐known, Nobel Prize winning transformation for producing alkenes. Unlike the alkenyl and aryl variants of the Heck reaction, the alkyl‐Heck reaction is still underdeveloped owing to the competitive side reactions of alkyl–palladium species. Herein, we describe the development of a deaminative alkyl‐Heck‐type reaction that proceeds through C?N bond activation by visible‐light photoredox catalysis. A variety of aliphatic primary amines were found to be efficient starting materials for this new process, affording the corresponding alkene products in good yields under mild reaction conditions. Moreover, this strategy was successfully applied to deaminative carbonylative alkyl‐Heck‐type reactions.     

A New Class of Non‐Racemic Chiral Macrocycles: A Conformational and Synthetic Study

Amino alcohols have been used to introduce non‐racemic chirality into macrocycles using a modular approach that relies on a Heck macrocyclisation reaction. A wide variety of macrocycles have been synthesised, and their structures studied using X‐ray crystallography and molecular modelling. A fragmentation reaction encountered during the use of (S)‐1,1‐dimethylvalinol revealed that carboxylic acids generate acylals under reaction conditions often used for Heck reactions.     

Sulfinate‐Salt‐Mediated Radical Relay Cyclization of Cyclic Ethers with 2‐Alkynylbenzonitriles toward 3‐Alkylated 1‐Indenones

A new sulfinate salt‐mediated radical relay for the completion of C(sp³)?H bond indenylation of cyclic ethers with readily available 2‐alkynylbenzonitriles by combining silver/tert‐butyl peroxide (TBHP) was established, providing a wide range of 3‐alkylated 1‐indenones with generally good yields. Interestingly, the current reaction system can tolerate an S‐centered radical and a C‐centered radical in one pot, in which the S‐centered radical promotes the formation of the C‐centered radical to induce a radical cascade without disturbing the reaction process. A reaction mechanism is also proposed based on control experiments.     

Bimetal‐Catalyzed Cascade Reaction for Efficient Synthesis of N‐Isopropenyl 1,2,3‐Triazoles via In‐Situ Generated 2‐Azidopropenes

A bimetal‐catalyzed cascade reaction for the synthesis of N‐isopropenyl 1,2,3‐triazoles in high yield is reported. This reaction involves the generation of 2‐azidopropenes in situ by C(sp³)‐OAr bond cleavage for click reaction and features a broad substrate scope, good functional group tolerance and readily available substrates.     

Copper‐Assisted/Copper‐Free Synthesis of Functionalized Dibenzo[b,f]oxepins and Their Analogs via a One‐Pot Tandem Reaction

A simple, convenient, and efficient method for the formation of functionalized dibenzo[b,f]oxepins and their analogs bearing both electron‐donating and electron‐withdrawing groups has been developed via a one‐pot cascade reaction. Most starting materials are commercially available 2‐(2‐hydroxyphenyl)acetonitriles and 2‐haloarylaldehydes. The procedure makes use of Cs₂CO₃ as the base, and DMF as solvent under copper‐assisted/copper‐free conditions. The reaction has a comprehensive group tolerance for substrates. Most of the reactions were complete within 1 h in good‐to‐excellent yields, and the reaction temperatures were relatively low. The protocol could be scaled up to grams without lowering the yield. A reaction mechanism was also proposed.     

Total Syntheses of (−)‐Strictosidine and Related Indole Alkaloid Glycosides

A collective synthesis of glycosylated monoterpenoid indole alkaloids is reported. A highly diastereoselective Pictet–Spengler reaction with α‐cyanotryptamine and secologanin tetraacetate as substrates, followed by a reductive decyanation reaction, was developed for the synthesis of (?)‐strictosidine, which is an important intermediate in biosynthesis. This two‐step chemical method was established as an alternative to the biosynthetically employed strictosidine synthase. Furthermore, after carrying out chemical and computational studies, a transition state for induction of diastereoselectivity in our newly discovered Pictet–Spengler reaction is proposed. Having achieved the first enantioselective total synthesis of (?)‐strictosidine in just 10 steps, subsequent bioinspired transformations resulted in the concise total syntheses of (?)‐strictosamide, (?)‐neonaucleoside A, (?)‐cymoside, and (?)‐3α‐dihydrocadambine.     

UV‐Induced Tetrazole‐Thiol Reaction for Polymer Conjugation and Surface Functionalization

A UV‐induced 1,3‐dipolar nucleophilic addition of tetrazoles to thiols is described. Under UV irradiation the reaction proceeds rapidly at room temperature, with high yields, without a catalyst, and in both polar protic and aprotic solvents, including water. This UV‐induced tetrazole‐thiol reaction was successfully applied for the synthesis of small molecules, protein modification, and rapid and facile polymer–polymer conjugation. The reaction has also been demonstrated for the formation of micropatterns by site‐selective surface functionalization. Superhydrophobic–hydrophilic micropatterns were successfully created by sequential modifications of a tetrazole‐modified porous polymer surface with hydrophobic and hydrophilic thiols. A biotin‐functionalized surface could be fabricated in aqueous solutions under long‐wavelength UV irradiation.     

Iron‐Catalyzed Radical Cleavage/C−C Bond Formation of Acetal‐Derived Alkylsilyl Peroxides

A novel radical‐based approach for the iron‐catalyzed selective cleavage of acetal‐derived alkylsilyl peroxides, followed by the formation of a carbon–carbon bond is reported. The reaction proceeds under mild reaction conditions and exhibits a broad substrate scope with respect to the acetal moiety and the carbon electrophile. Mechanistic studies suggest that the present reaction proceeds through a free‐radical process involving carbon radicals generated by the homolytic cleavage of a carbon–carbon bond within the acetal moiety. A synthetic application of this method to sugar‐derived alkylsilyl peroxides is also described.     

Density functional computational studies on the glucose and glycine Maillard reaction: Formation of the Amadori rearrangement products

Theoretical energy changes of various intermediates leading to the formation of the Amadori rearrangement products (ARPs) under different mechanistic assumptions have been calculated, by using open chain glucose (O‐Glu)/closed chain glucose (A‐Glu and B‐Glu) and glycine (Gly) as a model for the Maillard reaction. Density functional theory (DFT) computations have been applied on the proposed mechanisms under different pH conditions. Thus, the possibility of the formation of different compounds and electronic energy changes for different steps in the proposed mechanisms has been evaluated. B‐Glu has been found to be more efficient than A‐Glu, and A‐Glu has been found more efficient than O‐Glu in the reaction. The reaction under basic condition is the most favorable for the formation of ARPs. Other reaction pathways have been computed and discussed in this work. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008