Acylsilanes in Rhodium(III)‐Catalyzed Directed Aromatic C–H Alkenylations and Siloxycarbene Reactions with C?C Double Bonds

Acylsilanes are known to undergo a 1,2‐silicon‐to‐oxygen migration under thermal or photochemical conditions to form siloxycarbenes. However, there are few reports regarding the application of siloxycarbenes in organic synthesis and surprisingly, their reaction with C C double or triple bonds remains virtually unexplored. To facilitate such a study, previously inaccessible aromatic acylsilanes containing an ortho‐tethered C C double bond were identified as suitable substrates. To access these key intermediates, we developed a new synthetic method utilizing a rhodium‐catalyzed oxidative Heck‐type olefination involving the application of an acylsilane moiety as a directing group. When exposed to visible‐light irradiation, the ortho‐olefinated acylsilanes underwent a smooth intramolecular cyclization process to afford valuable indanone derivatives in quantitative yields. This result paves the way for the development of new transformations involving siloxycarbene intermediates.     

Acylsilanes in Iridium‐Catalyzed Directed Amidation Reactions and Formation of Heterocycles via Siloxycarbenes

Exposing ortho‐amido aroylsilanes to visible light or heat leads to cyclization reactions that provide N‐heterocyclic compounds via siloxycarbenes as key intermediates. The previously unreported starting materials have been prepared by directed amidations of aromatic acylsilanes in the presence of an iridium catalyst followed by N‐alkylation.     

Photochemical reactions. 148th communication. Photochemistry of acylsilanes: Preparation,photolyses, and thermolyses of α,β-unsaturated silyl ketones

The syntheses, photolyses, and thermolyses of the α,β-unsaturated silyl ketones (E/Z)-7, (E)- 8 , and (E)- 9 are described. On n,π*-excitation (λ > 347 mm), the aforementioned compounds undergo (E/Z)-isomerization followed by γ-H abstraction. The intermediate enols are trapped intermolecularly by siloxycarbenes leading to the dimeric acetals 27A + B, 30A + B , and 31A + B . In addition, the acylsilanes (E/Z)- 7 undergo photoisomerization by δ-H abstraction furnishing the acylsilanes 29A + B . Flash vacuum thermolyses (FVT) of (E/Z)- 7 , (E/Z)- 8 , and (E)- 9 give rise to intramolecular reactions of the siloxycarbene intermediates. Thus, FVT (520°) of (E)- and (Z)- 7 selectively leads to the enol silyl ethers 32 and (E)- 33 , respectively, arising from carbene insertion into an allylic C–-H bond. FVT of (E/Z)- 8 (560°) and (E)- 9 (600°) affords the trienol silyl ethers 34A + B and the cyclic silyl ethers 37A + B , respectively, which are formed by CH insertion of the siloxycarbenes. As further products of (E)- 8 and (E)- 9 , the bicyclic enol ethers 35 and 36 are formed, presumably via siloxycarbene addition to the cyclohexene C?C bond.     

Toward product control in ring‐opening oligomerization of 9H‐9‐borafluorenes

To get deep insights into the structure–reactivity relationship for ring‐opening oligomerization reactions toward targeted design of novel main‐chain boron‐containing materials, detailed DFT B97D/TZVP calculations are carried out to compare the ring‐opening oligomerization of both unsubstituted and tert‐butyl (tBu)‐substituted 9H?9‐borafluorenes. In contrast to substituent exchange between normal boranes, such reactions are initiated by substituent exchanges involving double B? C? B bridged intermediates. On tBu‐substitution, the B? C? B, and B? H? B bridged dimer intermediate is stabilized mainly due to enhanced barrier of 18.1 kcal/mol toward further trimerization channel and higher isomerization barrier of 22.5 kcal/mol toward the double B? H? B bridged dimer. In good agreement with available experiments, it is clearly shown that various product channels can be efficiently controlled by bulky substitution and by reaction temperatures, pointing out the way toward desired higher oligomers with improved thermal stability. © 2014 Wiley Periodicals, Inc.     

trans‐Carbocarbonation of Internal Alkynes through a Formal anti‐Carbopalladation/C−H Activation Cascade

An intramolecular Pd‐catalyzed cascade reaction is presented that consists of a formal anti‐carbopalladation of a C?C triple bond followed by C?H activation. As a result, oligocyclic ring systems with an embedded tetrasubstituted double bond are formed. The key to success in affording the trans geometry of the emerging double bond are alkyne units with residues that must not undergo β‐hydride elimination (e.g., t‐butyl or silyl groups). Silyl groups proved to be a perfect handle to further convert the tetrasubstituted alkenes. The evaluation of kinetic data with a deuterium‐labeled compound and X‐ray analyses of trapped intermediates provided additional insight into the catalytic cycle.     

Photochemically promoted transition metal-free cross-coupling of acylsilanes with organoboronic esters

Intermolecular carbon-carbon bond formation between acylsilanes and organoboronic esters was achieved by photoirradiation under almost neutral, transition metal-free conditions. In this reaction, siloxycarbenes generated by photoisomerization of acylsilanes reacted with boronic esters to give the formal B-C bond insertion intermediates, which underwent unique rearrangement to afford the cyclic α-alkoxyboronic esters. Acidic treatment of the resulting crude products under air furnished the cross-coupled ketones in good yields.     

Intramolecular Cyclopropanation of 1,4‐Dienes through Hydroboration–Homologation: Easy Access to Bicyclo[3.1.0]hexanes

An intramolecular cyclopropanation reaction involving B‐(1‐chloroalkyl)catecholborane intermediates generated from 1,4‐dienes through hydroboration with catecholborane and Matteson homologation was developed. This sequential procedure leading to bicyclo[3.1.0]hexanes involves the formation of three new sigma C?C bonds at the same carbon atom. A mechanistic study supports the involvement of carbocationic intermediates.     

Transition‐Metal‐Free Deconstructive Lactamization of Piperidines

One of the major challenges in organic synthesis is the activation or deconstructive functionalization of unreactive C(sp³)–C(sp³) bonds, which requires using transition or precious metal catalysts. We present here an alternative: the deconstructive lactamization of piperidines without using transition metal catalysts. To this end, we use 3‐alkoxyamino‐2‐piperidones, which were prepared from piperidines through a dual C(sp³)–H oxidation, as transitory intermediates. Experimental and theoretical studies confirm that this unprecedented lactamization occurs in a tandem manner involving an oxidative deamination of 3‐alkoxyamino‐2‐piperidones to 3‐keto‐2‐piperidones, followed by a regioselective Baeyer–Villiger oxidation to give N‐carboxyanhydride intermediates, which finally undergo a spontaneous and concerted decarboxylative intramolecular translactamization.     

Advancements in the Synthesis and Applications of Cationic N‐Heterocycles through Transition Metal‐Catalyzed C−H Activation

Cationic N‐heterocycles are an important class of organic compounds largely present in natural and bioactive molecules. They are widely used as fluorescent dyes for biological studies, as well as in spectroscopic and microscopic methods. These compounds are key intermediates in many natural and pharmaceutical syntheses. They are also a potential candidate for organic light‐emitting diodes (OLEDs). Because of these useful applications, the development of new methods for the synthesis of cationic N‐heterocycles has received a lot of attention. In particular, many C?H activation methodologies that realize high step‐ and atom‐economies toward these compounds have been developed. In this review, recent advancements in the synthesis and applications of cationic N‐heterocycles through C?H activation reactions are summarized. The new C?H activation reactions described in this review are preferred over their classical analogs.     

Palladium‐Catalyzed Cascade Double C—N Bond Activation: A New Strategy for Aminomethylation of 1,3‐Dienes with Aminals

A new palladium‐catalyzed selective aminomethylation of conjugated 1,3‐dienes with aminals via double C—N bond activation is described. This simple method provides an effective and rapid approach for the synthesis of linear α,β‐unsaturated allylic amines with perfect regioselectivity. Mechanistic studies disclosed that one palladium catalyst cleaved two distinct C—N bond to furnish a cascade double C—N bond activation, in which an allylic 1,3‐diamine and allylic 1,2‐diamine were initially formed as key intermediates through the palladium‐catalyzed C—N bond activation of aminal and the α,β‐unsaturated allylic amine was subsequently produced via palladium‐catalyzed C—N bond activation of the allylic diamines.     

Mononuclear Nonheme High‐Spin (S=2) versus Intermediate‐Spin (S=1) Iron(IV)–Oxo Complexes in Oxidation Reactions

Mononuclear nonheme high‐spin (S=2) iron(IV)–oxo species have been identified as the key intermediates responsible for the C?H bond activation of organic substrates in nonheme iron enzymatic reactions. Herein we report that the C?H bond activation of hydrocarbons by a synthetic mononuclear nonheme high‐spin (S=2) iron(IV)–oxo complex occurs through an oxygen non‐rebound mechanism, as previously demonstrated in the C?H bond activation by nonheme intermediate (S=1) iron(IV)–oxo complexes. We also report that C?H bond activation is preferred over C=C epoxidation in the oxidation of cyclohexene by the nonheme high‐spin (HS) and intermediate‐spin (IS) iron(IV)–oxo complexes, whereas the C=C double bond epoxidation becomes a preferred pathway in the oxidation of deuterated cyclohexene by the nonheme HS and IS iron(IV)–oxo complexes. In the epoxidation of styrene derivatives, the HS and IS iron(IV) oxo complexes are found to have similar electrophilic characters.     

Generation and Rearrangement of N,O‐Dialkenylhydroxylamines for the Synthesis of 2‐Aminotetrahydrofurans

A new diastereoselective route to 2‐aminotetrahydrofurans has been developed from N,O‐dialkenylhydroxylamines. These intermediates undergo a spontaneous C?C bond‐forming [3,3]‐sigmatropic rearrangement followed by a C?O bond‐forming cyclization. A copper‐catalyzed N‐alkenylation of an N‐Boc‐hydroxylamine with alkenyl iodides, and a base‐promoted addition of the resulting N‐hydroxyenamines to an electron‐deficient allene, provide modular access to these novel rearrangement precursors. The scope of this de novo synthesis of simple nucleoside analogues has been explored to reveal trends in diastereoselectivity and reactivity. In addition, a base‐promoted ring‐opening and Mannich reaction has been discovered to covert 2‐aminotetrahydrofurans to cyclopentyl β‐aminoacid derivatives or cyclopentenones.     

Synthesis of Azabicyclic Building Blocks for Daphniphyllum Alkaloid Intermediates Featuring N‐Trichloroacetyl Enamide 5‐endo‐trig Radical Cyclizations

A general procedure is reported for the synthesis of cis ring fused azapolycyclic compounds bearing an all‐carbon quaternary stereocenter at the ring fusion and an adequate functionalization for the assembly of new rings leading to advanced synthetic intermediates for Daphniphyllum alkaloid synthesis. The key carbon?carbon bond‐forming step in this approach is a radical cyclization of an N‐cycloalkenyl trichloroacetamide derivative involving a tetrasubstituted enamide to achieve polyfunctionalized lactams.     

Metal Olefin Complexes: Revisiting the Dewar−Chatt−Duncanson Model and Deriving Reactivity Patterns from Carbon‐13 NMR Chemical Shift

Metal olefin complexes that are ubiquitous intermediates in catalysis are investigated by a detailed analysis of their ¹³C‐NMR chemical shift tensors. This analysis allows evidencing specific electronic features, namely the olefin‐to‐metal σ‐donation and the metal‐to‐olefin π‐backdonation as proposed in the Dewar?Chatt?Duncanson model. Apart from these interactions, the chemical shift tensor analysis reveals an additional ligand‐to‐metal π‐donation of the olefin σ(C=C) orbital in systems with suitably oriented vacant d‐orbitals. This interaction which is not accounted for in the Dewar?Chatt?Duncanson model explains the reactivity of this type of metal olefin complexes towards oxidative cyclization (olefin insertion) and protonolysis.     

Efficient Selective Formation of C‐C Single Bonds and C˭C Double Bonds by NBS‐Promoted Oxidative Coupling of β‐Keto Esters

Abstract

A new application of NBS, which results in the oxidative coupling of β‐keto esters to selectively form C‐C single and C?C double bonds, can be controlled by the amount of NBS and t‐BuOK employed. This methodology adds a new entry to C‐C single and C?C double‐bond formation between active methylene groups under mild conditions with high selectivity.     

Carbon Monoxide Activation by a Molecular Aluminium Imide: C−O Bond Cleavage and C−C Bond Formation

Anionic molecular imide complexes of aluminium are accessible via a rational synthetic approach involving the reactions of organo azides with a potassium aluminyl reagent. In the case of K₂[( NON )Al(NDipp)]₂ ( NON =4,5‐bis(2,6‐diisopropylanilido)‐2,7‐di‐tert‐butyl‐9,9‐dimethyl‐xanthene; Dipp=2,6‐diisopropylphenyl) structural characterization by X‐ray crystallography reveals a short Al?N distance, which is thought primarily to be due to the low coordinate nature of the nitrogen centre. The Al?N unit is highly polar, and capable of the activation of relatively inert chemical bonds, such as those found in dihydrogen and carbon monoxide. In the case of CO, uptake of two molecules of the substrate leads to C?C coupling and C≡O bond cleavage. Thermodynamically, this is driven, at least in part, by Al?O bond formation. Mechanistically, a combination of quantum chemical and experimental observations suggests that the reaction proceeds via exchange of the NR and O substituents through intermediates featuring an aluminium‐bound isocyanate fragment.     

Tertiary α‐Silyl Alcohols by Diastereoselective Coupling of 1,3‐Dienes and Acylsilanes Initiated by Enantioselective Copper‐Catalyzed Borylation

An efficient synthesis of functionalized tertiary α‐silyl alcohols by an enantio‐ and diastereoselective copper‐catalyzed three‐component coupling of 1,3‐dienes, bis(pinacolato)diboron, and acylsilanes is reported. The reaction proceeds well with different 1,3‐dienes and a broad range of aryl‐ as well as alkenyl‐ but also alkyl‐substituted acylsilanes. The target compounds are formed with high regio‐, diastereo‐, and enantioselectivity (up to 99 % ee and d.r. >20:1) and are highly versatile synthetic building blocks.     

Cobalt‐Catalyzed Regio‐ and Stereoselective Hydroboration of Allenes

An efficient pincer‐ligand‐based cobalt‐complex‐catalyzed allene hydroboration affording Z‐allylic boronates is described. The reaction demonstrates an excellent regio‐ as well as Z‐stereoselectivity and a wide substrate scope that tolerates many functional groups. Based on solvent‐assisted electrospray ionization mass spectrometry (SAESI‐MS) studies, a rationale for the cobalt‐catalyzed hydroboration involving the highly selective insertion of an allene into the Co?H bond to form Z‐allylic cobalt intermediates is proposed.     

Chemoselective,Substrate‐directed Fluorination of Functionalized Cyclopentane β‐Amino Acids

This work describes a substrate‐directed fluorination of some highly functionalized cyclopentane derivatives. The cyclic products incorporating CH₂F or CHF₂ moieties in their structure have been synthesized from diexo‐ or diendo‐norbornene β‐amino acids following a stereocontrolled strategy. The synthetic study was based on an oxidative transformation of the ring carbon–carbon double bond of the norbornene β‐amino acids, followed by transformation of the resulted ?all cis“ and ?trans“ diformyl intermediates by fluorination with ?chemodifferentiation“.     

Synthesis of N‐Arylated 1,2‐Dihydroheteroaromatics Through the Three‐Component Reaction of Arynes with N‐Heteroaromatics and Terminal Alkynes or Ketones

The reaction of benzynes with N‐heteroaromatics including quinolines, isoquinolines, and pyridines and various terminal alkynes or ketones with an α‐hydrogen in the presence of KF and 18‐crown‐6 in THF at room temperature for 8 h gave various N‐arylated 1,2‐dihydroheteroaromatics in good to moderate yields. Some of these product structures are found in various naturally occurring and biologically active heterocyclic compounds. The reaction involves an unusual multiple construction of new C? C, C? N, and C? H bonds and the cleavage of a C? H bond in one pot. It is likely that the three‐component coupling proceeds through the nucleophilic addition of quinoline to benzyne, which generates a zwitterionic species. The latter then attracts a proton from terminal alkyne (or ketone) to generate an N‐arylated quinolinium cation and an acetylide anion. Further reaction of these two ions provides the final substituted 1,2‐dihydroquinolines. In the reaction, the terminal alkyne acts first as a proton donor and then as a nucleophile. The application of a three‐component coupling reaction product, 1,2‐dihydro‐2‐pyridinyl alkyne in a stereospecific [4+2] Diels–Alder cycloaddition reaction with N‐phenyl maleimide to give an isoquinuclidine derivative, an important core present in various natural products, is demonstrated.