Gallium Trihalide Catalyzed Sequential Addition of Two Different Carbon Nucleophiles to Esters by Using Silyl Cyanide and Ketene Silyl Acetals

A sequential addition of silyl cyanide and ketene silyl acetals to esters was achieved by a gallium trihalide catalyst to produce β‐cyano‐β‐siloxy esters. This is the first example of the sequential addition of two different carbon nucleophiles to esters. The employment of lactones provided α,α‐disubstituted cyclic ethers with a cyano group and an ester moiety. A variety of esters and lactones are applicable to this reaction system.     

Lewis base activation of Lewis acids: catalytic, enantioselective addition of silyl ketene acetals to aldehydes

The concept of Lewis base activation of Lewis acids has been reduced to practice for catalysis of the aldol reaction of silyl ketene acetals and silyl dienol ethers with aldehydes. The weakly acidic species, silicon tetrachloride (SiCl4), can be activated by binding of a strongly Lewis basic chiral phosphoramide, leading to in situ formation of a chiral Lewis acid. This species has proven to be a competent catalyst for the aldol addition of acetate-, propanoate-, and isobutyrate-derived silyl ketene acetals to conjugated and nonconjugated aldehydes. Furthermore, vinylogous aldol reactions of silyl dienol ethers are also demonstrated. The high levels of regio-, anti diastereo-, and enantioselectivity observed in these reactions can be rationalized through consideration of an open transition structure where steric interactions between the silyl cation complex and the approaching nucleophile are dominant.     

alpha-thiocyanation of carbonyl and beta-dicarbonyl compounds using (dichloroiodo)benzene-lead(II) thiocyanate

The combination reagent (dichloroiodo)benzene and lead(II) thiocyanate in dichloromethane effects oxidation of various enol silyl ethers, ketene silyl acetals, and beta-dicarbonyl compounds, thereby providing an efficient and convenient method for alpha-thiocyanation of carbonyl and beta-dicarbonyl compounds.     

Coupling Reaction of Enol Derivatives with Silyl Ketene Acetals Catalyzed by Gallium Trihalides

A cross‐coupling reaction between enol derivatives and silyl ketene acetals catalyzed by GaBr₃ took place to give the corresponding α‐alkenyl esters. GaBr₃ showed the most effective catalytic ability, whereas other metal salts such as BF₃?OEt₂, AlCl₃, PdCl₂, and lanthanide triflates were not effective. Various types of enol ethers and vinyl carboxylates as enol derivatives are amenable to this coupling. The scope of the reaction with silyl ketene acetals was also broad. We successfully observed an alkylgallium intermediate by using NMR spectroscopy, suggesting a mechanism involving anti‐carbogallation among GaBr₃, an enol derivative, and a silyl ketene acetal, followed by syn‐β‐alkoxy elimination from the alkylgallium. Based on kinetic studies, the turnover‐limiting step of the reaction using a vinyl ether and a vinyl carboxylate involved syn‐β‐alkoxy elimination and anti‐carbogallation, respectively. Therefore, the leaving group had a significant effect on the progress of the reaction. Theoretical calculations analysis suggest that the moderate Lewis acidity of gallium would contribute to a flexible conformational change of the alkylgallium intermediate and to the cleavage of the carbon?oxygen bond in the β‐alkoxy elimination process, which is the turnover‐limiting step in the reaction between a vinyl ether and a silyl ketene acetal.     

Catalytic enantioselective aldol reaction to ketones

An enantioselective aldol reaction between ketones and ketene silyl acetals is described using CuF-chiral phosphine as a catalyst. The key for high enantioselectivity was the development of a novel ligand derived from Taniaphos combined with the unique accelerative effect of PhBF3K. These conditions are applicable to various substrates such as aromatic, aliphatic, and heteroaromatic ketones. In the case of substituted nucleophiles, the reaction proceeds well. The diastereoselectivity is independent of ketene silyl acetal geometry. This is the first example of a catalytic enantio- and diastereoselective aldol reaction to ketones using ketene silyl acetals.     

Mesoporous aluminosilicate-catalyzed Mukaiyama aldol reaction of aldehydes and acetals

A mesoporous aluminosilicate (Al-MCM-41) was found to be an effective heterogeneous catalyst for the reaction of both aldehydes and acetals with silyl enol ethers or ketene silyl acetals to give the corresponding aldol adducts in moderate to high yields. The remarkable high catalytic activity of Al-MCM-41 over amorphous silica-alumina and aluminum-free mesoporous silicate was observed in the reaction. The solid acid catalyst could be recovered easily by filtration and the recovered catalyst was reusable in the same reactions without a significant loss of catalytic activity.     

Mild and efficient pentafluorophenylammonium triflate (PFPAT)-catalyzed C-acylations of enol silyl ethers or ketene silyl (Thio)acetals with acid chlorides

A pentafluorophenylammonium triflate (PFPAT) catalyst (5 mol %) successfully promoted C-acylation of enol silyl ethers with acid chloride to produce various beta-diketones (12 examples; 62-92% yield). Similarly, C-acylation of ketene silyl acetals or ketene silyl thioacetals (i.e., crossed Claisen condensation) proceeded smoothly to provide not only alpha-monoalkylated beta-keto (thio)esters but also thermodynamically unfavorable (less accessible) alpha,alpha-dialkylated beta-keto (thio)esters in good to excellent yield (38 examples; 60-92% yield).     

Diastereoselective additions of nucleophiles to alpha-acetoxy ethers using the alpha-(trimethylsilyl)benzyl auxiliary

We report the diastereoselective addition of a variety of nucleophiles to alpha-(trimethylsilyl)benzyl-substituted oxocarbenium ions. The oxocarbenium ions are generated from alpha-acetoxy ethers, which are easily prepared via reductive acetylation of esters. The alpha-(trimethylsilyl)benzyl auxiliary produces good to excellent facial selectivity with a variety of nucleophiles, including silyl enol ethers, silyl ketene acetals, allylsilanes, and crotylsilanes. The utility of this auxiliary is further demonstrated in a complex ketone aldol coupling reaction. [reaction: see text]     

Facile synthesis of pyrroles via Rh(II)-catalyzed transannulation of 1-tosyl-1,2,3-triazoles with silyl or alkyl enol ethers

A novel Rh(II)-catalyzed transannulation of 1-tosyl-1,2,3-triazoles with silyl or alkyl enol ethers has been developed, which enables the facile synthesis of substituted pyrroles in a regiocontrollable manner. Moreover, the methodology could be extended to access 3-pyrrolin-2-one derivatives with silyl ketene acetals used as the reaction partner.     

N-heterocyclic carbene-catalyzed silyl enol ether formation

N-Heterocyclic carbenes (NHCs) were found to catalyze the silyl transfer from trialkylsilyl ketene acetals to ketones. In the presence of a catalytic amount of NHC 3 (IAd, 0.1 to 5 mol %), a series of enolizable ketones as well as cyclohexanecarboxaldehyde were efficiently converted into the corresponding silyl enol ethers at 23 degrees C in THF.     

Trimethyl Orthoacetate and Ethylene Glycol Mono‐Vinyl Ether as Enolate Surrogates in Enantioselective Iridium‐Catalyzed Allylation

Trimethyl orthoacetate and ethylene glycol mono‐vinyl ether are employed in iridium‐catalyzed enantioselective allylation reactions. The method documented enables their convenient use as surrogates for silyl ketene acetals and silyl enol ethers to prepare γ,δ‐unsaturated esters and protected aldehydes with excellent enantioselectivity. The utility of this novel method has been demonstrated by its implementation in a formal enantioselective synthesis of the meroterpenoid (+)‐conicol.     

Lewis base activation of Lewis acids: catalytic, enantioselective addition of glycolate-derived silyl ketene acetals to aldehydes

A catalytic system involving silicon tetrachloride and a chiral, Lewis basic bisphosphoramide catalyst is effective for the addition of glycolate-derived silyl ketene acetals to aldehydes. It was found that the sense of diastereoselectivity could be modulated by changing the size of the substituents on the silyl ketene acetals. In general, the trimethylsilyl ketene acetals derived from methyl glycolates with a large protecting group on the alpha-oxygen provide enantiomerically enriched alpha,beta-dihydroxy esters with high syn-diastereoselectivity, whereas the tert-butyldimethylsilyl ketene acetals derived from bulky esters of alpha-methoxyacetic acid provide enantiomerically enriched alpha,beta-dihydroxy esters with high anti-diastereoselecitvity.     

Addition of activated olefins to cyclic N-acyliminium ions in ionic liquids

Organoindate(III) ionic liquid (BMI·InCl₄) was successfully employed in the nucleophilic addition of allyltrimethylsilane, silyl enol ethers and ketene silyl acetals to in situ generated cyclic N-acyliminium ions at room temperature without the need of an external Lewis acid. The corresponding α-substituted heterocycles were obtained in good yields and the recovered ionic liquid phase could be reused at least three times.     

Mucohalic acid in Lewis acid catalyzed Mukaiyama aldol reaction: a concise method for highly functionalized γ-substituted γ-butenolides

The first Mukaiyama aldol reaction on mucohalic acid (1a/b) has been achieved. Reaction of 1 with various ketene silyl acetals or silyl enol ethers in the presence of a Lewis acid provides the γ-substituted γ-butenolides in good to excellent yield.     

Indium Tribromide Catalyzed Coupling Reaction of Enol Ethers with Silyl Ketene Imines toward the Synthesis of β,γ‐Unsaturated Nitriles

Herein, a coupling reaction of enol ethers with silyl ketene imines in the presence of catalytic amounts of InBr₃ and Me₃SiBr is described. Kinetic studies have revealed that an indium catalyst and Me₃SiBr accelerated the coupling process and the regeneration of the catalyst, respectively. Various types of enol ethers and silyl ketene imines are applicable. In addition, a formal synthesis of verapamil was achieved by using this novel coupling reaction.     

Mechanism of Mukaiyama-Michael Reaction of Ketene Silyl Acetal: Electron Transfer or Nucleophilic Addition?

Mechanism of Mukaiyama-Michael reaction of ketene silyl acetal has been discussed. The competition reaction employing various types of ketene silyl acetals reveals that those bearing more substituents at the beta-position react preferentially over less substituted ones. However, when ketene silyl acetals involve bulky siloxy and/or alkoxy group(s), less substituted compounds react preferentially. The Lewis acids play an important role in these reactions. Enhanced preference for the more sterically demanding Michael adducts is obtained with Bu(2)Sn(OTf)(2), SnCl(4), and Et(3)SiClO(4) in the former reaction while TiCl(4) gives the highest selectivity for the less sterically demanding products in the latter case. These results are interpreted in terms of alternative reaction mechanisms. The reaction of less bulky ketene silyl acetals are initiated by electron transfer from these compounds to a Lewis acid. On the other hand, bulkier ketene silyl acetals undergo a ubiquitous nucleophilic reaction. Such a mechanistic change is discussed based on a variety of experimental results as well as the semiempirical PM3 MO calculations.     

Experimental and theoretical studies on Mannich-type reactions of chiral non-racemic N-(benzyloxyethyl) nitrones

The nucleophilic addition of both silyl ketene acetals and lithium enolates derived from methyl acetate to chiral non-racemic N-(benzyloxyethyl)nitrones has been studied both experimentally and theoretically. Aromatic nitrones showed lower reactivity that aliphatic nitrones and the addition of the silyl ketene acetal led to lower selectivities than the addition of the corresponding lithium enolate. Whereas low selectivity was obtained for the addition of the silyl ketene acetal, only one diastereomer could be detected in all cases for the addition of lithium enolate to aliphatic nitrones. The synthetic utility of the two chiral auxiliaries employed lies in the preparation of enantiomeric compounds. DFT theoretical calculations confirmed the stepwise mechanism for the addition of silyl ketene acetals to nitrones and are in good agreement with the observed experimental results.     

Rhenium-catalyzed reaction of carbonyl compounds with ketene silyl acetals

It was found that rhenium complex is an effective catalyst for the reaction of carbonyl compounds with ketene silyl acetals. A wide range of β-silyloxy esters is obtained by the treatment of carbonyl compounds with ketene silyl acetals in the presence of a catalytic amount of ReBr(CO)₅ in moderate to good yields.     

Aminoboranes as "compatible" iminium ion generators in aminative C-C bond formations

Aminoboranes have been shown to be highly efficient and mild iminium ion generators in the Mannich-type aminative coupling of aldehydes with silyl ketene acetals. By using aminoboranes bearing bulky amino groups, such as a diisopropylamino group, free secondary amines can be successfully used as the amino component in a three-component Mannich reaction with aldehydes and silyl ketene acetals.     

Synthesis of 2,6-disubstituted dihydropyrans via an efficient BiBr3-initiated three component, one-pot cascade

The rapid synthesis of cis-2,6-disubstituted dihydropyrans is achieved in a three-component, one-pot cascade reaction. BiBr₃-mediated addition of ketene silyl acetals or silyl enol ethers to β,γ-unsaturated cis-4-trimethylsilyl-3-butenal provides a Mukaiyama aldol adduct containing a vinylsilane moiety tethered to a silyl ether. Addition of a second aldehyde initiates a domino sequence involving intermolecular addition followed by an intramolecular silyl-modified Sakurai (ISMS) reaction. Isolated yields of this one-pot reaction vary from 44 to 80% and all compounds were isolated as the cis-diastereomers (10 examples).