Synthesis and Rearrangement of Silylated Oxy-Cope Systems

Addition of allyl or vinyl organometallic reagents to chiral a,b\alpha,\beta- or b,g\beta,\gamma -unsaturated acylsilanes afforded stereoselectively 3-silylated 3-hydroxy-1,5-dienes that are stereoselectively converted to d,e\delta,\varepsilon-unsaturated acylsilanes by the thermal oxy-Cope rearrangement. The rearrangement is restricted to compounds possessing an (alkoxy)methyl substituent at the silicon moiety; upon heating, analogous compounds with the t-BuMe₂_2Si group in the 3-position led to decomposition only. The (alkoxy)methyl group at silicon is supposed to act as a weak internal base, which accelerates the rearrangment reaction.     

Synthesis and Rearrangement of Silylated Oxy-Cope Systems

Addition of allyl or vinyl organometallic reagents to chiral a,b\alpha,\beta- or b,g\beta,\gamma -unsaturated acylsilanes afforded stereoselectively 3-silylated 3-hydroxy-1,5-dienes that are stereoselectively converted to d,e\delta,\varepsilon-unsaturated acylsilanes by the thermal oxy-Cope rearrangement. The rearrangement is restricted to compounds possessing an (alkoxy)methyl substituent at the silicon moiety; upon heating, analogous compounds with the t-BuMe₂_2Si group in the 3-position led to decomposition only. The (alkoxy)methyl group at silicon is supposed to act as a weak internal base, which accelerates the rearrangment reaction.     

Uncatalyzed Hydroamination of Electrophilic Organometallic Alkynes: Fundamental,Theoretical, and Applied Aspects

Simple reactions of the most used functional groups allowing two molecular fragments to link under mild, sustainable conditions are among the crucial tools of molecular chemistry with multiple applications in materials science, nanomedicine, and organic synthesis as already exemplified by peptide synthesis and “click” chemistry. We are concerned with redox organometallic compounds that can potentially be used as biosensors and redox catalysts and report an uncatalyzed reaction between primary and secondary amines with organometallic electrophilic alkynes that is free of side products and fully “green”. A strategy is first proposed to synthesize alkynyl organometallic precursors upon addition of electrophilic aromatic ligands of cationic complexes followed by endo hydride abstraction. Electrophilic alkynylated cyclopentadienyl or arene ligands of Fe, Ru, and Co complexes subsequently react with amines to yield trans‐enamines that are conjugated with the organometallic group. The difference in reactivities of the various complexes is rationalized from the two‐step reaction mechanism that was elucidated through DFT calculations. Applications are illustrated by the facile reaction of ethynylcobalticenium hexafluorophosphate with aminated silica nanoparticles. Spectroscopic, nonlinear‐optical and electrochemical data, as well as DFT and TDDFT calculations, indicate a strong push–pull conjugation in these cobalticenium– and Fe– and Ru–arene–enamine complexes due to planarity or near‐planarity between the organometallic and trans‐enamine groups involving fulvalene iminium and cyclohexadienylidene iminium mesomeric forms.     

Cu/SaBox-Catalyzed Photoinduced Coupling of Acylsilanes with Alkynes

The transition metal-catalyzed cross-coupling reaction with Fischer metal carbene intermediates bearing an electron-rich alkoxyl or siloxyl group remains a big challenge due to the lack of readily available corresponding carbene precursors. Herein, we report the coupling of alkynes with the Fischer-type copper carbene species bearing a α-siloxyl group, which could be in situ generated from acylsilanes catalytically under photoirradiation and redox-neutral conditions. The side-arm modified bisoxazoline (SaBox) ligands prove to be crucial for this coupling reaction, which provides the corresponding alkynyl alcohol in high yields with remarkable heterocycle tolerance and broad substrate scope.     

Isolation of keto-s-phenylthioxime of [23]cyclophane-1,2-dione. Re-visited contraction of 1,2,5-thiadiazole ring incorporated in a [23]cyclophane bridge by phenylmagnesium bromide

[2³]Paracyclophane derivative 3 of keto-S-phenylthioxime which is the hydrolyzed product of the hypothetical intermediate in the reaction of 1,2,5-thiadiazole with organometallic reagents, was obtained, together with diketone 1 , in the reaction of 1,2,5-thiadiazolo[2³]paracyclophane 2 with two equivalents of phenylmagnesium bromide. Contrary, [2³]metacyclophane 7 gave only diketone 12 in the reaction with phenylmagnesium bromide under the same conditions.     

Reaction of acylsilanes with α-sulfinyl carbanions: regioselective synthesis of silyl enol ethers

The reaction of acylsilanes with α-sulfinyl carbanions such as α-lithioalkyl sulfoxide is described. The reaction proceeds to give silyl enol ethers preferentially through the initial formation of the α-silyl alkoxide intermediates. In particular, the products derived from enolizable acylsilanes were the regio-defined silyl enol ethers that cannot be obtained by usual enolization of the corresponding unsymmetrical ketones with base.     

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 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.     

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.     

A General Method for the Vinylation of Nitrones. Synthesis of Allyl Hydroxylamines and Allyl Amines

An examination of the vinylation of several nitrones is presented. Whereas a complete diastereofacial discrimination was observed upon the addition of vinyl organometallic reagents to α-alkoxy nitrones, the same reaction with α-amino nitrones gave syn adducts in all cases, with the only exception of a L-serine-derived α-amino monoprotected nitrone. The obtained allyl hydroxylamines were easily transformed into synthetically valuable allyl amines.     

Diastereoselective alkylation and reduction of β-alkoxyacylsilanes: stereoselective construction of three contiguous stereogenic centers

The nucleophilic addition reaction to acylsilanes, having stereogenic centers at the α and β positions, derived from the aldol reaction of dimethyl acetals and acylsilane silyl enol ethers gives the corresponding α-silylalcohols in high yields with excellent diastereoselectivity. The protiodesilylation of α-silylalcohols proceeds with complete retention of the configuration. In addition, the reduction of acylsilanes having stereogenic centers at the α and β positions affords the corresponding α-silylalcohols in good yields with high diastereoselectivity similarly to the nucleophilic addition. And the treatment of acylsilanes having a phenyl group on silicon atom with fluoride ion results in the formation of phenyl carbinol derivatives via migration of the phenyl group with high diastereoselectivity.     

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.     

Photochemical reactions. 152nd Communication. Photochemistry of acylsilanes; photolysis and thermolysis of cyclopropyl silyl ketones

The photolysis and thermolysis of the Cyclopropyl silyl ketones 3, 4 , and 5 are described. On n,π* excitation, the silyl ketones 3 and 4 undergo a Norrish-type-II reaction involving γ-H abstraction, cyclopropyl ring cleavage followed by retro-enolization to the acylsilanes 6 and (E/Z)- 12 , respectively. As a common product of 3 and 4 , the dihydrofuran 7 is formed via the alternative C(α)-C(β) cleavage of the cyclopropyl moiety. Compounds 6 , 7 , and (E/Z)- 12 are new types of acylsilane photoproducts. The irradiation of acylsilane 5 gave the analogous dihydrofuran 15 as the only product. On photolysis of 3 and 4 , products 8A + B and 13A + B , derived from a siloxy carbene intermediate, were found as well. On thermolysis of 3 and 4 , the acylsilanes 6 (80%), and (E)- 12 (33%) and (Z)- 12 (34%), respectively, are formed as the only products. Their formation may occur via a [1, 5] sigmatropic H-shift. The thermolysis of 5 gave the diene 16 whose formation can be explained by insertion of a siloxycarbene into the neighboring cyclopropane leading to the cyclobutene 28 as thermally unstable intermediate.     

Reaction of silyldihalomethyllithiums with nitriles: formation of alpha-keto acylsilanes via azirines and 1,3-rearrangement of silyl group from C to N

A synthesis of alpha-keto acylsilanes, where 2-bromo-2H-azirine participates as a key intermediate, is reported. The reaction of silyldibromomethyllithium with aryl nitriles provides alpha-keto acylsilanes in good yields. Interestingly, silyldichloromethyllithium induces aza-1,3-Brook rearrangement of the silyl group in th reaction with nitriles. The rearrangement enables a three-component coupling reaction in a one-pot operation.     

Synthesis of 1-hydrocarbon substituted cyclopropyl silyl ketones

The synthesis of cyclopropyl silyl ketones possessing a hydrocarbon group at 1-position of three-membered ring was investigated. The reaction of sulfoxonium ylide with α,β-unsaturated acylsilanes derived from α,β-unsaturated aldehydes did not afford the desired acylsilane derivatives. Instead, the corresponding silyl enol ethers were yielded exclusively. On the other hand, the Corey-Chaykovsky cyclopropanation of α-substituted α,β-unsaturated aldehydes proceeded well to give 1-substituted cyclopropyl aldehydes. The silyl substitution of formyl proton in the obtained aldehydes via umpolung of carbonyl group afforded the target acylsilanes.     

Catalytic additions of acylsilanes to imines: an acyl anion strategy for the direct synthesis of alpha-amino ketones

The addition of acylsilanes to imines catalyzed by neutral carbenes (or zwitterions) generated in situ from readily available thiazolium salts is described. The general reaction successfully utilizes acylsilanes as carbonyl anion precursors and is tolerant of a range of structural diversity on the acylsilane or imine electrophile. The overall reaction utilizes easily available precursors and directly accesses protected alpha-amino ketones in the correct oxidation state.     

The reaction of allenylsilanes with α,β-unsaturated acylsilanes: new annulation approaches to five and six-membered carbocyclic compounds

The reaction of α,β-unsaturated acylsilanes with allenylsilanes can be directed to produce either five or six-membered carbocyclic compounds.     

Photochemical reactions. 139th Communication. Photochemistry of acylsilanes: 1. Siloxcarbene formation versus γ-H-abstraction

The Syntheses and the photolyses of the acylsilane 1 and the corresponding methyl ketone 2 are described. On n,π*-excitation, the silyl ketone 1 as well as the methyl ketone 2 undergo a Norrish type II reaction involving γ-H-abstraction and fragmentation to the diene 12 , and acetone ( 20 ) or the acylsilane 26 , respectively. The methyl ketone 2 , but not the acylsilane 1 , isomerizes to cyclobutanols ( 21A - D ). Additionally, compound 1 shows photochemical behavior typical of acylsilanes undergoing rearrangement to the siloxycarbene intermediate c . Insertion of c into the O? H-ond of the enol 28 leads to compound 13 . Initial trapping of the siloxycarbene c by H₂O, however, gives rise to the formation of compounds 16 – 18 . As minor photolysis products of 1 , compounds 14 and (Z)- 15 were formed; however, on vapor phase thermolysis (520°) of 1 , compounds 14 and (E/Z)- 15 were obtained in 92% combined yield. To a small extent the acylsilane 1 also undergoes Norrish type I cleavage leading to the acid 19 .     

In situ stabilization of Pd(0) nanoparticles into a mixture of natural carbohydrate beads: A novel and highly efficient heterogeneous catalyst system for Heck coupling reactions

A convenient, mild and cost‐effective synthesis of palladium nanoparticles stabilized by a mixture of natural carbohydrate beads (gum arabic and pectin) as a new bio‐organometallic catalyst is reported. Powder X‐ray diffraction, transmission and scanning electron microscopies and energy‐dispersive X‐ray and UV–visible spectroscopies were employed to characterize this supported Pd nanoparticles/gum arabic/pectin catalyst. The nanocatalyst exhibited efficient activity in Mizoroki–Heck cross‐coupling reactions between various aryl halides and n ‐butyl acrylate under solvent‐free conditions. The catalyst can easily be recovered from the reaction system and reused several times with high yields. The products were obtained in short reaction times with excellent yields.     

Thiazolium-catalyzed additions of acylsilanes: a general strategy for acyl anion addition reactions

A strategy utilizing N-heterocyclic carbenes (NHCs) derived from thiazolium salts has been developed for the generation of carbonyl anions from acylsilanes. Synthetically useful 1,4-diketones and N-phosphinoyl-alpha-aminoketones have been prepared in good to excellent yields via NHC-catalyzed additions of acylsilanes to the corresponding alpha,beta-unsaturated systems and N-phosphinoylimines. These organocatalytic reactions are air- and water-tolerant methods to execute robust carbonyl anion addition reactions. Additionally, polysubstituted aromatic furans and pyrroles have been efficiently synthesized in a one-pot process using this carbonyl anion methodology. The addition of alcohols to the reaction renders the process catalytic in thiazolium salt. In an effort to synthesize a potential intermediate along the proposed reaction pathway, silylated thiazolium carbinols have been identified to provide good yields of carbonyl anion addition products when subjected to the standard reaction conditions in the presence of suitable electrophiles.