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.     

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.     

Lewis base activation of Lewis acids. Catalytic enantioselective addition of silyl enol ethers of achiral methyl ketones to aldehydes

A highly enantioselective addition of silyl enol ethers derived from simple methyl ketones is described. The catalyst system of silicon tetrachloride activated by a chiral bisphosphoramide (R,R)-7 effectively promotes the addition of a variety of unsubstituted silyl enol ethers to aromatic, olefinic, and heteroaromatic aldehydes in excellent yield. [reaction: see text]     

Lewis base activation of Lewis acids: catalytic, enantioselective vinylogous aldol addition reactions

The generality of Lewis base catalyzed, Lewis acid mediated, enantioselective vinylogous aldol addition reactions has been investigated. The combination of silicon tetrachloride and chiral phosphoramides is a competent catalyst for highly selective additions of a variety of alpha,beta-unsaturated ketone-, 1,3-diketone-, and alpha,beta-unsaturated amide-derived dienolates to aldehydes. These reactions provided high levels of gamma-site selectivity for a variety of substitution patterns on the dienyl unit. Both ketone- and morpholine amide-derived dienol ethers afforded high enantio- and diastereoselectivity in the addition to conjugated aldehydes. Although alpha,beta-unsaturated ketone-derived dienolate did not react with aliphatic aldehydes, alpha,beta-unsaturated amide-derived dienolates underwent addition at reasonable rates affording high yields of vinylogous aldol product. The enantioselectivities achieved with the morpholine derived-dienolate in the addition to aliphatic aldehydes was the highest afforded to date with the silicon tetrachloride-chiral phosphoramide system. Furthermore, the ability to cleanly convert the morpholine amide to a methyl ketone was demonstrated.     

Lewis base activation of Lewis acids. Vinylogous aldol addition reactions of conjugated N,O-silyl ketene acetals to aldehydes

N,O-Silyl dienyl ketene acetals derived from unsaturated morpholine amides have been developed as highly useful reagents for vinylogous aldol addition reactions. In the presence of SiCl4 and the catalytic action of chiral phosphoramide (R,R)-3, N,O-silyl dienyl ketene acetal 8 undergoes high-yielding and highly site-selective addition to a wide variety of aldehydes with excellent enantioselectivity. Of particular note is the high yields and selectivities obtained from aliphatic aldehydes. Low catalyst loadings (2-5 mol %) can be employed. The morpholine amide serves as a useful precursor for further synthetic manipulation.     

Catalytic formation of C-O bonds by alkene activation: Lewis acid-cycloisomerisation of olefinic alcohols

Tin(IV) trifluoromethanesulfonate has been found to be an excellent catalyst for the cycloisomerisation of non-activated and differently substituted olefinic alcohols to cyclic ethers.     

Lewis acid-promoted conjugate addition of dienol silyl ethers to nitroalkenes: synthesis of 3-substituted azepanes

A novel gamma-selective conjugate addition of 1-silyl-substituted dienol ethers to nitroalkenes activated by Lewis acids has been developed. The resulting alpha,beta-unsaturated acylsilanes undergo photoinduced protodesilylation to afford the corresponding enals, which can be conveniently transformed into azepanes under appropriate reductive conditions.     

Efficient and practical catalytic vinylogous aldol reaction of dioxinone-derived silyl dienol ethers with aromatic aldehydes

Vinylogous Mukaiyama-aldol reaction was realized by use of dioxinone-derived silyl dienol ethers and various aldehydes in the presence of highly catalytic amounts of bismuth triflate. The reaction proceeds rapidly and affords the corresponding β-hydroxy-1,3-dioxin-4-ones in very good to excellent yields (up to 98%).     

Gold(I)-catalyzed propargyl Claisen rearrangement

Homoallenic alcohols are prepared from propargyl vinyl ethers using a trinuclear gold(I)-oxo complex, [(Ph3PAu)3O]BF4, as a catalyst for propargyl Claisen rearrangement at room temperature. The gold(I)-catalyzed reaction is effective for a diverse collection of propargyl vinyl ethers, including substrates containing aryl and alkyl groups at the propargylic position, and hydrogen, aryl, and alkyl substituents at the alkyne terminus. Tertiary propargyl vinyl ethers can be employed in the reaction, at slightly elevated temperatures, to afford tetrasubstituted allenes. Importantly, the rearrangement of 1,2-disubstituted vinyl ethers proceeds with excellent diastereoselectivity, and the rearrangement of chiral nonracemic propargyl vinyl ethers proceeds with excellent chirality transfer to furnish enantioenriched allenes.     

Rhodium-catalyzed asymmetric coupling reaction of allylic ethers with arylboronic acids

An asymmetric allylic substitution of simple allylic ethers with arylboronic acids in the presence of a rhodium(I)/(R)-DTBM-SEGPHOS catalyst has been developed. The reactions proceeded smoothly at room temperature to give the corresponding branch products with excellent regioselectivities and good to excellent enantioselectivities.     

Vinyl ketones to allenes: preparation of 1,3-dien-2-yl triflates and their application in Pd-catalyzed reactions with soft nucleophiles

[chemical reaction: see text]. A general route of converting alkenyl ketones to functionalized allenes was developed. Substituted 1,3-dien-2-yl triflates, which were prepared from the alkenyl ketones via silyl dienol ethers, were excellent substrates for the palladium-catalyzed reaction with soft nucleophiles giving the multisubstituted allenes in high yields. Comparison between the dienyl triflates and analogous bromodienes in the Pd-catalyzed reaction was studied as well.     

The preparation and reactions of dienol ester and dienol ester derivatives of hagemann's ester and its t-butyl analogue

The efficient conversion of Hagemann's ester and its t-butyl analogue into dienol ethers and dienol esters, and reactions of the derived dienolates with electrophiles is described.     

Phenylthiomethylstannylation of silyl enol ethers and silyl dienol ethers

Silyl enol ethers (2) react with tributyl [(phenylthio) chloromethyl] stannane (1) in the presence of Zinc bromide to give β-phenylthiomethylstannyl ketones (3) in good yields. Silyl dienol ethers (4) mainly give products (5) due to γ-attack, under these conditions.     

Auto‐Tandem Catalysis with Frustrated Lewis Pairs for Reductive Etherification of Aldehydes and Ketones

Herein we report that a single frustrated Lewis pair (FLP) catalyst can promote the reductive etherification of aldehydes and ketones. The reaction does not require an exogenous acid catalyst, but the combined action of FLP on H₂, R‐OH or H₂O generates the required Brønsted acid in a reversible, “turn on” manner. The method is not only a complementary metal‐free reductive etherification, but also a niche procedure for ethers that would be either synthetically inconvenient or even intractable to access by alternative synthetic protocols.     

Novel sequential 1,4-Brook rearrangement-Wittig reaction: new one-pot approach for silyl dienol ethers

A novel one-pot synthetic method of silyl dienol ethers via 1,4-Brook rearrangement-Wittig reaction sequence has been developed. This tandem reaction proceeded via the intramolecular silyl migration step, which enabled stereoselective formation of phosphorane intermediates. The reaction is operationally simple and high yielding, thus providing a new useful formula for silyl dienol ether synthesis.     

Synthesis of substituted acetylenes, aryl-alkyl ethers, 2-alkene-4-ynoates and nitriles using heterogeneous mesoporous Pd-MCM-48 as reusable catalyst

Pd-MCM-48 has been employed as a heterogeneous catalyst for the synthesis of substituted acetylenes via Sonogashira reactions under copper and amine-free reaction conditions. In addition, the catalyst exhibited excellent regioselectivity for primary alcohols towards C-O coupling leading to formation of alkyl-aryl ethers in high yields. A green procedure for the stereoselective synthesis of 2-alkene-4-ynoates and nitriles from the reactions of vic-(E)-diiodoalkenes with activated alkenes has also been demonstrated using Pd-MCM-48 catalyst. The catalyst was easily recovered from the reaction mixture by filtration and reused for at least six times with minimal loss of activity.     

The γ-alkylation of enones using silyl dienol ethers: The effect of changing the electrophile and of changing the silyl group

Phenylthiomethyl chloride (3) and the trimethylsilyl dienol ether (2) of crotonophenone react to give the lowest level of γ-attack of a range of carbon electrophiles and trimethylsilyl dienol ethers; the γ-selectivity for this reaction can be raised from 45:55 to 85:15 by changing the silyl group from trimethylsilyl to triphenylsilyl.     

Preparation of silyl polyenol ethers by carbonyl olefination of silyl esters

Silyl enol ethers were produced by the carbonyl olefination of silyl esters with titanium carbene complexes generated by the desulfurizative titanation of thioacetals. The regioselective preparation of silyl dienol and trienol ethers has been achieved by using unsaturated silyl esters and thioacetals.     

Formamides as Lewis Base Catalysts in SN Reactions—Efficient Transformation of Alcohols into Chlorides,Amines, and Ethers

A simple formamide catalyst facilitates the efficient transformation of alcohols into alkyl chlorides with benzoyl chloride as the sole reagent. These nucleophilic substitutions proceed through iminium‐activated alcohols as intermediates. The novel method, which can be even performed under solvent‐free conditions, is distinguished by an excellent functional group tolerance, scalability (>100 g) and waste‐balance (E‐factor down to 2). Chiral substrates are converted with excellent levels of stereochemical inversion (99 %→≥95 % ee). In a practical one‐pot procedure, the primary formed chlorides can be further transformed into amines, azides, ethers, sulfides, and nitriles. The value of the method was demonstrated in straightforward syntheses of the drugs rac‐Clopidogrel and S‐Fendiline.     

A Lewis Acid-Catalyzed Procedure for the Conversion of 2-Methoxyethoxymethyl Ethers to Carboxylic Esters

A procedure for the conversion of 2-methoxy-ethoxymethyl (MEM) ethers to carboxylic esters employed ferric chloride (0.4 equivalents) and a carboxylic anhydride (14 equivalents) and exhibited selectivity for the MEM ether functionality in the presence of benzyl ethers.