Rhodium(II)‐Catalyzed Enantioselective Synthesis of Troponoids

We report a rhodium(II)‐catalyzed highly enantioselective 1,3‐dipolar cycloaddition reaction between the carbonyl moiety of tropone and carbonyl ylides to afford troponoids in good to high yields with excellent enantioselectivity. We demonstrate that α‐diazoketone‐derived carbonyl ylides, in contrast to carbonyl ylides derived from diazodiketoesters, undergo [6+3] cycloaddition reactions with tropone to yield the corresponding bridged heterocycles with excellent stereoselectivity.     

1,4-silatropy of S-alpha-silylbenzyl thioesters: a convenient route to silyl enol and dienol ethers accompanied by C-C bond formation via thiocarbonyl ylides

A novel convenient method for the generation of thiocarbonyl ylides from readily accessible starting materials and the first synthetic application of in situ generated ylides in the synthesis of silyl enol and dienol ethers, accompanied by C-C bond formation, is described. Under completely neutral conditions without any catalyst or additive, thermal reactions of S-alpha-silylbenzyl thioesters in sealed tubes at 180 degrees C provided silyl enol and dienol ethers in good to excellent yields with high stereoselectivities. This procedure consists of a multistep reaction in a one-pot process, i.e., 1,4-silatropy of S-alpha-silylbenzyl thioesters to give thiocarbonyl ylides, 1,3-electrocyclization of the ylides to give thiiranes, and the extrusion of sulfur from thiiranes to give silyl enol and dienol ethers.     

Total Syntheses of (+)‐Polygalolide A and (+)‐Polygalolide B: Elucidation of the Absolute Stereochemistry and Biogenetic Implications

The total syntheses of (+)‐polygalolide A and (+)‐polygalolide B have been completed by using a carbonyl ylide cycloaddition strategy. Three of the four stereocenters, including two consecutive tetrasubstituted carbon atoms at C2 and C8, were incorporated through internal asymmetric induction from the stereocenter at C7 by a [Rh₂(OAc)₄]‐catalyzed carbonyl ylide formation/intramolecular 1,3‐dipolar cycloaddition sequence. The arylmethylidene moiety of these natural products was successfully installed by a Mukaiyama aldol‐type reaction of a silyl enol ether with a dimethyl acetal, followed by elimination under basic conditions. We have also developed an alternative approach to the carbonyl ylide precursor based on a hetero‐Michael reaction. This approach requires 18 steps, and the natural products were obtained in 9.8 and 9.3 % overall yields. Comparison of specific rotations of the synthetic materials and natural products suggests that polygalolides are biosynthesized in nearly racemic forms through a [5+2] cycloaddition between a fructose‐derived oxypyrylium zwitterion with an isoprene derivative.     

Synthesis of Chiral Tetrasubstituted Azetidines from Donor–Acceptor Azetines via Asymmetric Copper(I)‐Catalyzed Imido‐Ylide [3+1]‐Cycloaddition with Metallo‐Enolcarbenes

The all‐cis stereoisomers of tetrasubstituted azetidine‐2‐carboxylic acids and derivatives that possess three chiral centers have been prepared in high yield and stereocontrol from silyl‐protected Z‐γ‐substituted enoldiazoacetates and imido‐sulfur ylides by asymmetric [3+1]‐cycloaddition using chiral sabox copper(I) catalysis followed by Pd/C catalytic hydrogenation. Hydrogenation of the chiral p‐methoxybenzyl azetine‐2‐carboxylates occurs with both hydrogen addition to the C=C bond and hydrogenolysis of the ester.     

Catalytic Asymmetric [3+1]‐Cycloaddition Reaction of Ylides with Electrophilic Metallo‐enolcarbene Intermediates

The first asymmetric [3+1]‐cycloaddition was successfully achieved by copper(I) triflate/double‐sidearmed bisoxazoline complex catalyzed reactions of β‐triisopropylsilyl‐substituted enoldiazo compounds with sulfur ylides. This methodology delivered a series of chiral cyclobutenes in good yields with high enantio‐ and diastereoselectivities (up to 99 % ee , and >20:1 d.r.). Additionally, the [3+1]‐cycloaddition of catalytically generated metallo‐enolcarbenes was successfully extended to reaction with a stable benzylidene dichlororuthenium complex.     

Total syntheses of (+)-polygalolide a and (+)-polygalolide b: elucidation of the absolute stereochemistry and biogenetic implications

The total syntheses of (+)-polygalolide?A and (+)-polygalolide?B have been completed by using a carbonyl ylide cycloaddition strategy. Three of the four stereocenters, including two consecutive tetrasubstituted carbon atoms at C2 and C8, were incorporated through internal asymmetric induction from the stereocenter at C7 by a [Rh(2) (OAc)(4)]-catalyzed carbonyl ylide formation/intramolecular 1,3-dipolar cycloaddition sequence. The arylmethylidene moiety of these natural products was successfully installed by a Mukaiyama aldol-type reaction of a silyl enol ether with a dimethyl acetal, followed by elimination under basic conditions. We have also developed an alternative approach to the carbonyl ylide precursor based on a hetero-Michael reaction. This approach requires 18 steps, and the natural products were obtained in 9.8 and 9.3?% overall yields. Comparison of specific rotations of the synthetic materials and natural products suggests that polygalolides are biosynthesized in nearly racemic forms through a [5+2] cycloaddition between a fructose-derived oxypyrylium zwitterion with an isoprene derivative.     

Sulfilimines as Versatile Nitrene Transfer Reagents: Facile Access to Diverse Aza‐Heterocycles

We herein report the unprecedented synthesis of diverse biologically important aza‐heterocycles by employing sulfilimines as nitrene transfer reagents. This class of sulfur‐based aza‐ylides had not been successfully used for gold nitrene transfer before. This work contains an efficient generation of α‐imino gold carbenes by N?S cleavage of sulfilimines. These gold carbenes undergo C?H insertion, cyclopropanation, and nucleophilic attack to form indoles (44 examples), 3‐azabicyclo[3.1.0]hexan‐2‐imines (24 examples), and imidazoles (3 examples). Our study represents a unique gold‐catalyzed reaction between alkynes and sulfur ylides, and also includes the first aza‐heterocycle synthesis that proceeds by intermolecular nitrene transfer followed by cyclopropanation of the α‐imino gold carbenes. Moreover, an unexpected synthesis of 4‐acylquinolines (3 examples) from 2‐acylphenyl sulfilimines and propargylic silyl ether derivatives by a 1,2‐hydride shift onto the α‐imino gold carbene and a subsequent Mukaiyama aldol cyclization was discovered.     

Synthetic Studies on and Mechanistic Insight into [W(CO)5(L)]‐Catalyzed Stereoselective Construction of Functionalized Bicyclo[5.3.0]decane Frameworks

Stereoselective preparation of a variety of synthetically useful functionalized bicyclo[5.3.0]decane derivatives was achieved by tandem cyclization of 3‐siloxy‐1,3,9‐triene‐7‐yne derivatives based on the electrophilic activation of alkynes catalyzed by [W(CO)₅(L)]. The reaction proceeded smoothly under photoirradiation, and various substrates were cyclized to give the corresponding bicyclic compounds with up to four chiral centers stereospecifically. Reactions of siloxydienes with a silyl substituent as an equivalent of a hydroxyl group also proceeded with wide generality to afford silyl‐substituted bicyclo[5.3.0]decanes, which were highly useful as synthetic intermediates. Stereochemical studies concerning the silyl enol ether moiety suggested that two types of reaction pathway for the formation of seven‐membered rings were present. The reaction of (Z)‐enol silyl ethers proceeded through Cope rearrangement of cis‐divinylcyclopropane intermediates, and that of (E)‐enol silyl ethers by 1,4‐addition of the dienyl tungsten species at the position δ to the metal atom. In the reactions of siloxydiene derivatives with silyl substituents, all possible diastereomers could be synthesized stereoselectively by changing the geometry of the silyl enol ether and enyne moieties.     

A Chiral N,N′‐Dioxide–ZnII Complex Catalyzes the Enantioselective [2+2] Cycloaddition of Alkynones with Cyclic Enol Silyl Ethers

A highly efficient enantioselective [2+2] cycloaddition between alkynones and cyclic enol silyl ethers was developed by using a chiral N,N′‐dioxide‐zinc(II) complex as a catalyst. This method functions well for a variety of terminal alkynes as well as cyclic enol silyl ethers, with good to excellent enantioselectivity (up to 97 % ee). This is also the first successful example for the catalytic enantioselective [2+2] cycloaddition of internal alkynes with cyclic enol silyl ethers to give fully substituted cyclobutenes. Meanwhile, the desired cyclobutene product can easily be transformed into fused cyclobutane derivatives.     

Acid anhydrides as alternatives to acid chlorides in the palladium‐catalyzed reaction with silacyclobutanes

The palladium‐catalyzed reaction of acid anhydrides with silacyclobutane gives a mixture of cyclic silyl enol ether, carboxy(propyl)silane, and 3‐(carboxysilyl)ketone. In the presence of N,N‐dicyclohexylcarbodiimido (DCC), the reaction preferentially provides a cyclic silyl enol ether in a good yield. In addition, the palladium‐catalyzed reaction of benzoic acid with silacyclobutane in the presence of two equivalents of DCC also affords a cyclic silyl enol ether in a moderate yield. Copyright © 2001 John Wiley & Sons, Ltd.     

Iron‐Catalyzed Decarboxylative (4+1) Cycloadditions: Exploiting the Reactivity of Ambident Iron‐Stabilized Intermediates

The first example of iron‐catalyzed decarboxylative (4+1) cycloaddition reactions is described in this publication. By using this method, a wide range of functionalized indoline products were prepared from easily available vinyl benzoxazinanones and sulfur ylides in high yields and selectivities. A possible reaction pathway involving an allylic iron intermediate is discussed based on a series of control experiments and density‐functional theory calculations.     

Visible‐Light‐Driven Photocatalytic Activation of Inert Sulfur Ylides for 3‐Acyl Oxindole Synthesis

Bicarbonyl‐substituted sulfur ylide is a useful, but inert reagent in organic synthesis. Usually, harsh reaction conditions are required for its transformation. For the first time, it was demonstrated that a new, visible‐light photoredox catalytic annulation of sulfur ylides under extremely mild conditions, permits the synthesis of oxindole derivatives in high selectivities and efficiencies. The key to its success is the photocatalytic single‐electron‐transfer (SET) oxidation of the inert amide and acyl‐stabilized sulfur ylides to reactive radical cations, which easily proceeds with intramolecular C?H functionalization to give the final products.     

Asymmetric Synthesis of Tetrahydroquinolines through a [3+2] Cycloaddition Controlled by Dienamine Catalysis

A dienamine‐mediated enantioselective 1,3‐dipolar cycloaddition catalyzed by a chiral prolinol silyl ether catalyst has been developed. Removal of the benzamide group of the intermediates could furnish chiral C‐1 substituted tetrahydroisoquinolines (see scheme) in high yields and excellent stereoselectivities.     

Conversion of Carbonyl Compounds to Olefins via Enolate Intermediate

A general and efficient protocol to synthesize substituted olefins from carbonyl compounds via nickel catalyzed C—O activation of enolates was developed. Besides ketones, aldehydes were also suitable substrates for the presented catalytic system to produce di‐ or tri‐ substituted olefins. It is worth noting that this approach exhibited good tolerance to highly reactive tertiary alcohols, which could not survive in other reported routes for converting carbonyl compounds to olefins. This method also showed good regio‐ and stereo‐selectivity for olefin products. Preliminary mechanistic studies indicated that the reaction was accomplished through nickel catalyzed C—O activation of enolates, thus offering helpful contribution to current enol chemistry.     

Visible‐Light‐Driven Aza‐ortho‐quinone Methide Generation for the Synthesis of Indoles in a Multicomponent Reaction

A visible‐light‐driven radical‐mediated strategy for the in situ generation of aza‐ortho ‐quinone methides from 2‐vinyl‐substituted anilines and alkyl radical precursors is described. This process enables an efficient multicomponent reaction of 2‐vinylanilines, halides, and sulfur ylides, and has a wide substrate scope and good functional group tolerance. Treatment of the cycloaddition products with a base leads to densely functionalized indoles in a single‐flask operation.     

A carbocationic route to 3-substituted 1,4-cycloheptadienes

The Lewis acid catalysed reaction of 5-chloro-1, 3-cycloheptadiene 4 with silyl enol ethers yields -cycloheptadienyl substituted carbonyl compounds in high yield. Since 4 is easily prepared from cycloheptatriene, and the cycloheptadienyl cation 3 is preferably attacked at 3-position, this reaction opens an efficient access to 3-substituted 1,4-cycloheptadienes.     

Comparison of Cu‐ZSM‐5 Zeolites and Cu‐MOF‐505 Metal‐Organic Frameworks as Heterogeneous Catalysts for the Mukaiyama Aldol Reaction: A DFT Mechanistic Study

The density functional theory (DFT) model ONIOM(M06L/6‐311++G(2df,2p):UFF was employed to reveal the catalytic activity of Cu^II in the paddle‐wheel unit of the metal‐organic framework (MOF)‐505 material in the Mukaiyama aldol reaction compared with the activity of Cu‐ZSM‐5 zeolites. The aldol reaction between a silyl enol ether and formaldehyde catalyzed by the Lewis acidic site of both materials takes place through a concerted pathway, in which the formation of the C? C bond and the transfer of the silyl group occurs in a single step. MOF‐505 and Cu‐ZSM‐5 are predicted to be efficient catalysts for this reaction as they strongly activate the formaldehyde carbonyl carbon electrophile, which leads to a considerably lower reaction barrier compared with the gas‐phase system. Both MOF‐505 and Cu‐ZSM‐5 catalysts stabilize the reacting species along the reaction coordinate, thereby lowering the activation energy, compared to the gas‐phase system. The activation barriers for the MOF‐505, Cu‐ZSM‐5, and gas‐phase system are 48, 21, and 61 kJ mol^?1, respectively. Our results show the importance of the enveloping framework by stabilizing the reacting species and promoting the reaction.     

Dirhodium(II)‐Catalyzed Annulation of Enoldiazoacetamides with α‐Diazoketones: An Efficient and Highly Selective Approach to Fused and Bridged Ring Systems

A dirhodium(II)‐catalyzed annulation reaction between two structurally different diazocarbonyl compounds furnishes the donor–acceptor cyclopropane‐fused benzoxa[3.2.1]octane scaffold with excellent chemo‐, regio‐, and diastereoselectivity under exceptionally mild conditions. The composite transformation occurs by [3+2]‐cycloaddition between donor–acceptor cyclopropenes generated from enoldiazoacetamides and carbonyl ylides formed from intramolecular carbene–carbonyl cyclization in one pot with one catalyst. The annulation products can be readily transformed into benzoxa[3.3.1]nonane and hexahydronaphthofuran derivatives with exact stereocontrol. This method allows the efficient construction of three fused and bridged ring systems, all of which are important skeletons of numerous biologically active natural products.     

Ruthenium Catalyzed C−H Acylmethylation of N‐Arylphthalazine‐1,4‐diones with α‐Carbonyl Sulfoxonium Ylides: Highway to Diversely Functionalized Phthalazino‐fused Cinnolines

A direct ortho‐Csp²‐H acylmethylation of 2‐aryl‐2,3‐dihydrophthalazine‐1,4‐diones with α‐carbonyl sulfoxonium ylides is achieved through a Ru^II‐catalyzed C?H bond activation process. The protocol featured high functional group tolerance on the two substrates, including aryl‐, heteroaryl‐, and alkyl‐substituted α‐carbonyl sulfoxonium ylides. Thereafter, 2‐(ortho‐acylmethylaryl)‐2,3‐dihydrophthalazine‐1,4‐diones were used as potential starting materials for the expeditious synthesis of 6‐arylphthalazino[2,3‐a]cinnoline‐8,13‐diones and 5‐acyl‐5,6‐dihydrophthalazino[2,3‐a]cinnoline‐8,13‐diones under Lawesson's reagent and BF₃?OEt₂ mediated conditions, respectively. Of these, the BF₃?OEt₂‐mediated cyclization proceeded in DMSO as a solvent and a methylene source via dual C?C and C?N bond formations.     

A Visible‐Light‐Driven Iminyl Radical‐Mediated C−C Single Bond Cleavage/Radical Addition Cascade of Oxime Esters

A room‐temperature, visible‐light‐driven N‐centered iminyl radical‐mediated and redox‐neutral C?C single bond cleavage/radical addition cascade reaction of oxime esters and unsaturated systems has been accomplished. The strategy tolerates a wide range of O‐acyl oximes and unsaturated systems, such as alkenes, silyl enol ethers, alkynes, and isonitrile, enabling highly selective formation of various chemical bonds. This method thus provides an efficient approach to various diversely substituted cyano‐containing alkenes, ketones, carbocycles, and heterocycles.