Michael addition of stannyl ketone enolate to alpha,beta-unsaturated esters catalyzed by tetrabutylammonium bromide and an ab initio theoretical study of the reaction course

Michael addition of stannyl ketone enolates to alpha,beta-unsaturated esters was accomplished in the presence of a catalytic amount of tetrabutylammonium bromide (Bu(4)NBr). Other typical systems using lithium enolate or silyl enolate with catalysts (TiCl(4) or Bu(4)NF) failed to give the desired products. The bromide anion from Bu(4)NBr coordinates to the tin center in enolate to accelerate the conjugate addition where a five-coordinated tin species was generated. The coordination of the bromide anion significantly raises the HOMO level of tin enolate and enhances its nucleophilicity. The conjugate addition provides the intermediate Michael adduct, which has an ester enolate moiety, and the adduct immediately transforms to alpha-stannyl gamma-ketoester by keto-enol tautomerization. This step contributes to the stabilization of the product system and leads to a thermodynamically favorable reaction course. An ab initio calculation reveals that the activation energy in the reaction using the bromide anion is lower than that of the reaction without using it. The transition state in either reaction course has a linear structure, not a cyclic one. This system can be applied to a variety of tin enolates and alpha,beta-unsaturated carbonyls involving enoates, enones, and unsaturated amides.     

A new method for synthesis of α,α-disubstituted carbonyl compounds from carbonyl compounds with one-carbon homologation through β-oxido carbenoid rearrangement as the key reaction

The addition reaction of carbonyl compounds with lithium α-sulfinyl carbanions of 1-chloroalkyl p-tolyl sulfoxides gave adducts, α-chloro β-hydroxy sulfoxides, in high to quantitative yields. The adducts were first treated with a base to give alkoxides, which were treated with i-PrMgCl or t-BuLi to give β-oxido carbenoids via a sulfoxide-metal exchange reaction. The β-oxido carbenoid rearrangement then took place to afford the enolates with one-carbon elongation. The enolate intermediates were found to be able to be trapped with electrophiles such as aldehydes, ethyl chloroformate, benzoyl chloride, haloalkanes to give α,α-disubstituted carbonyl compounds in moderate to good yields. This method provides a new and efficient way for synthesis of α,α-disubstituted carbonyl compounds from carbonyl compounds with one-carbon homologation in only two synthetic operations.     

Cross-coupling reaction of alpha-chloroketones and organotin enolates catalyzed by zinc halides for synthesis of gamma-diketones

The reaction of tin enolates 1 with alpha-chloro- or bromoketones 2 gave gamma-diketones (1,4-diketones) 3 catalyzed by zinc halides. In contrast to the exclusive formation of 1,4-diketones 3 under catalytic conditions, uncatalyzed reaction of 1 with 2 gave aldol-type products 4 through carbonyl attack. NMR study indicates that the catalyzed reaction includes precondensation between tin enolates and alpha-haloketones providing an aldol-type species and their rearrangement of the oxoalkyl group with leaving halogen to produce 1,4-diketones. The catalyst, zinc halides, plays an important role in each step. The carbonyl attack for precondensation is accelerated by the catalyst as Lewis acid and the intermediate zincate promotes the rearrangement by releasing oxygen and bonding with halogen. Various types of tin enolates and alpha-chloro- and bromoketones were applied to the zinc-catalyzed cross-coupling. On the other hand, the allylic halides, which have no carbonyl moiety, were inert to the zinc-catalyzed coupling with tin enolates. The copper halides showed high catalytic activity for the coupling between tin enolates 1 and organic halides 7 to give gamma,delta-unsaturated ketones 8 and/or 9. The reaction with even chlorides proceeded effectively by the catalytic system.     

卤代烷反应中取代和消去竞争的教学设计

在卤代烷的取代和消去反应中,进攻试剂均为带负电的实体或多电子基团,因此取代和消去的竞争是卤代烷教学内容的重点和难点。本文介绍我们对这部分教学内容的组织和设计,使学生更好地理解反应底物、进攻试剂和反应条件对优势反应及产物的影响。该教学设计对培养学生的分析能力、思考能力和灵活应用知识的能力具有重要作用。     

Highly efficient and stereoselective synthesis of beta-glycolipids

beta-Galactosylceramide and glycolipid analogues were prepared in high yield and with complete chemo and stereoselectivity by reaction of alpha-iodo glycosides with stannyl ceramides, formed in situ. TBAI was used to activate both the iodogalactose and the stannyl ether.     

Intramolecular Michael reactions of aliphatic aldehyde enolates generated by imidazolium carbenes

Due to the high reactivity of the formyl group under either basic or acidic reaction conditions required for the direct generation of aldehyde enolates, intramolecular Michael additions of aldehyde enolates to α,β-unsaturated carbonyl compounds have been underexplored for the stereoselective synthesis of carbocyclic compounds. The intramolecular Michael reaction of aldehyde enolates generated by imidazolium carbenes was explored for the synthesis of cyclopentane aldehydes. The imidazolium carbenes were used as Brønsted bases to directly generate the aldehydes enolates.     

[Z]-1-[2-(三芳基锡基)乙烯基]环辛醇的合成和性质

本文用三苯基氢化锡、三对甲苯基氢化锡作为锡氢化试剂与1-乙炔基环辛醇进行反应, 合成了两个有机锡化合物: [Z]-1-[2-(三苯基锡基)乙烯基]环辛醇(1)和[Z]-1-[2-(三对甲苯基锡基)乙烯基]环辛醇(2), 并测定了1的晶体结构。1和2分别与ICl, Br2, I~2反应, 得到六个有机锡一卤化物和三个有机锡二卤化物(3-11)。有机锡二卤化物6和一卤化物5与KOH乙醇溶液反应, 分别得到相应的锡氧化物和锡氢氧化物(12, 13)。有机锡二卤化物8分别与含氮双齿配体[2,2'-联吡啶(Bipy),5-硝基-1,10-邻菲罗啉(Nphen),8-羟基喹啉(Oxin)]反应, 得到三个相应的配合物(14-16)。十六个新化合物通过元素分析、锡含量测定、IR、^1H NMR测定对其结构进行了表征, 同时提出了1和2的生成反应历程。     

Short communication: An alternative and effective catalyst for the silastannation of arylacetylenes with Me3SiSnBu3 at room temperature

The palladium‐catalyzed silastannation of acetylenes with tributyl(trimethylsilyl)stannane in the presence of triethylphosphite is reported for the first time. The reaction occurs at room temperature to give (Z)‐silyl(stannyl)ethenes in high yields. The protodemetallation of the resulting adducts with HCl–tetraethylammonium chloride is described first, which demonstrates that the reaction is governed only by the stability of a carbonium ion arising from the protonation to (Z)‐silyl(stannyl)ethenes rather than the hard and soft acid and base principle, i.e. the β‐cation stabilization effect (σ–π stabilization one) of a stannyl group in the carbonium ion is rather significant. Copyright © 2004 John Wiley & Sons, Ltd.     

Mechanism of the double aldol reaction: the first spectroscopic characterization of a carbon-bound boron enolate derived from carboxylic esters

The novel doubly borylated enolate is identified as an intermediate of the double aldol reaction of acetate esters. As a precursor to the formation of the doubly borylated enolate, carbon-bound boron enolates of carboxylic esters are spectroscopically characterized for the first time. When 2,6-diisopropylphenyl acetate (10d) is treated with c-Hex(2)BOTf (1.3 equiv) and triethylamine (1.5 equiv) in CDCl(3), the corresponding mono-enolate is formed as a mixture of oxygen- (11d) and carbon-bound (12d) forms in 71% and 20% yields, respectively. The structures of these enolates have been unambiguously determined by NMR spectroscopy. Investigation of the enolization of a series of substituted aryl acetates shows that the steric factor of the acetate affects the degree of the mono-enolate (as a mixture of oxygen- and carbon-bound enolates) and the doubly borylated enolate formation. Studies also revealed that oxygen- and carbon-bound boron enolates exist as equilibrium mixtures and that a proton transfer process occurs between oxygen- and carbon-bound enolates. The doubly borylated enolate formation is general for a variety of carbonyl compounds. Besides acetate esters, carbonyl containing compounds, such as acetic acid, dimethylacetamide, methoxyacetone, and 3-acetyl-2-oxazolidinone, also produce the doubly borylated enolates when treated with c-Hex(2)BOTf (2.5 equiv) and triethylamine (3.0 equiv). A plausible pathway of the double aldol reaction involving a carbon-bound boron enolate as a key intermediate is proposed.     

Generation of (E)-silylketene acetals in a Rhodium-DuPhos catalyzed two-step reductive aldol reaction

[reaction: see text]. Mechanistic studies employing in situ NMR analysis implicate intermediate silicon enolates as reactive intermediates in the Rh-DuPhos catalyzed two-step reductive aldol reaction with Cl(2)MeSiH. These enolates undergo noncatalyzed reaction with a variety of aldehydes to give the derived syn-aldol adduct in high yields and diastereoselection.     

Base-promoted reactions of bridged ketones and 1,3- and 1,4-haloalkyl azides: competitive alkylation vs azidation reactions of ketone enolates

The reactions of 1,3- and 1,4-haloalkyl azides with enolates of 2-norbornanone (and a ring-expanded analog) afford polycyclic 1,2,3-triazolines in good yields. The reaction occurs by the initial azidation of the ketone enolate, followed in order by triazoline formation and O-alkylation. An interesting element of this process is the preferential reaction of the alkyl azide with an enolate anion as opposed to the more familiar reaction of the alkyl halide (including Cl and I derivatives). Reactions of acyclic or monocyclic enolates generally lead to 1,2,3-triazoles but none of the alternative C-alkylation product.     

Allylstannylation of carbon-carbon and carbon-oxygen unsaturated bonds via a radical chain process

In the presence of a radical initiator, allyltributylstannanes bearing an electron-withdrawing group at the beta-position smoothly reacted with electron-deficient terminal alkenes to give allylstannylated products in good yields. The stannyl group was introduced into the terminal carbon with high regioselectivity. The allylstannylation of homochiral 8-phenylmenthyl acrylate proceeded with moderate to good diastereoselectivity. Terminal and electron-deficient internal alkynes as well efficiently underwent the radical-initiated allylstannylation in an anti addition mode. The reaction of terminal alkynes showed the same regioselectivity as that of terminal alkenes. The present radical reaction was applicable to allylation of aromatic aldehydes and ketones.     

Mechanistic and synthetic aspects of the reaction of alkyl esters of phosphorus with trimethylstannyl halides

The reaction of trimethylstannyl halides with trialkyl phosphates has been studied. The results are interpreted in terms of a mechanism involving a trimethylstannyloxyphosphonium salt intermediate. The much lower reactivity of the stannyl halides compared with their silicon analogs is explained by the lower ionization of the stannyl halide phosphate complexes and the unfavourable direction of the decomposition of the phosphonium salt intermediate. The reaction may be useful in synthesis of phosphates containing only one O-stannyl group, which can be used in generation of the acid function or replaced in reactions with compounds containing active halogen.     

Photochemical cleavage of benzylic stannanes

Photolysis of benzylic stannanes leads to efficient homolytic cleavage to form benzylic and stannyl radicals. The reaction proceeds via the excited singlet state of the benzyl stannane.     

Stannyl ester cyclizations

Alpha halo stannyl esters react with alkenes to afford lactones. The reaction is catalyzed by AIBN. The reaction proceeds best with electron rich alkenes. The mechanistic aspects of this novel reaction are discussed. This reaction can also be conducted intramolecularly to produce bicyclic lactones. An approach to the lignan system is presented.     

A versatile approach to the synthesis of 4,5-dioxoaporphine and 3,4-dioxocularine alkaloids. One-Pot sequential C/B ring formation from arylacetamides

Cyclization of biarylacetamides to their phenanthrene derivatives is promoted by oxalyl chloride/stannyl chloride. The reaction proceeds with a second cyclization in which the oxalyl fragment acts as an -dicarbonyl transfer agent to give 4,5-dioxoaporphine alkaloids in a single step. This double cyclization was also applied to aryloxyphenyl acetamides to give the corresponding 3,4-dioxocularine alkaloids. Decarbonylated aristocularine alkaloids were also formed in this case.     

Ruthenium-catalyzed decarboxylative allylation of nonstabilized ketone enolates

[reaction: see text] Bipyridyl(pentamethylcyclopentadienyl)ruthenium chloride is an efficient catalyst for the formal [3,3] rearrangement of allyl beta-ketoesters. The mechanism of the transformation involves formation of pi-allyl ruthenium intermediates, which are selectively attacked at the more substituted allyl terminus by freely diffusing enolates. Decarboxylation of beta-ketocarboxylates allows generation of enolates under extremely mild conditions.     

Asymmetric allylic alkylation of ketone enolates: an asymmetric Claisen surrogate

[reaction: see text] The combination of catalytic palladium(0) and Trost ligand provides an effective catalyst for the rearrangement of allyl beta-ketoesters. The mechanism of the transformation involves formation of pi-allyl palladium intermediates which undergo enantioselective attack by ketone enolates. Decarboxylation of beta-ketocarboxylates allows regiospecific generation of enolates under extremely mild conditions.     

Development of catalytic asymmetric reactions via chiral palladium enolates

This article describes the generation of chiral palladium enolates and their application to several kinds of catalytic asymmetric reactions. Two methods to generate chiral enolates were developed using novel cationic palladium complexes 1 and 2 . In these processes, water or a hydroxo ligand on palladium metal plays an important role as a nucleophile to promote the transmetallation or as a Brønsted base to abstract an acidic α‐proton of the carbonyl group. These enolates showed sufficient reactivity with various electrophiles. Using a chiral Pd enolate as a key intermediate, highly enantioselective reactions such as catalytic aldol reactions, Mannich‐type reactions, Michael reactions, and fluorination reactions were developed. The unique structures of the palladium enolate complexes were elucidated and reaction mechanisms are proposed. © 2004 The Japan Chemical Journal Forum and Wiley Periodicals, Inc. Chem Rec 4: 231–242; 2004: Published online in Wiley InterScience ( www.interscience.wiley.com ) DOI 10.1002/tcr.20017     

Property and reactivity of fluoro(silyl)acetylenes and fluoro(stannyl)acetylenes

Fluoro(silyl)acetylenes and fluoro(stannyl)acetylenes underwent a radical addition reaction of THF to furnish the corresponding fluorinated cyclic ethers in moderate to good yields. These intriguing addition reaction proved to proceed via a radical reaction mechanism.