Catalytic asymmetric hydroxymethylation of silicon enolates using an aqueous solution of formaldehyde with a chiral scandium complex

Catalytic asymmetric hydroxymethylation of silicon enolates has been achieved. In this reaction, an aqueous solution of formaldehyde can be used to realize an easy and safe procedure, and high enantioselectivities have been obtained. This is the first example of catalytic asymmetric reactions in aqueous media with a chiral scandium complex.     

Bismuth triflate-chiral bipyridine complexes as water-compatible chiral Lewis acids

[reaction: see text] Catalytic asymmetric hydroxymethylation of silicon enolates with an aqueous formaldehyde solution has been developed using a chiral bismuth complex. This is the first example of highly enantioselective reactions using a chiral bismuth catalyst in aqueous media. In this paper, we have added Bi(OTf)(3)-1 complex as a "water-compatible Lewis acid". Bi(OTf)3 is unstable in the presence of water but is stabilized by the basic ligand.     

Anionic, in situ generation of formaldehyde: a very useful and versatile tool in synthesis

A very simple, safe and powerful method for the in situ generation of formaldehyde at low temperature in anhydrous conditions is described. This new tool avoids the use of gaseous formaldehyde and is suitable for basic carbon nucleophiles which cannot be generated in aqueous reaction media. Various substrates, including organolithium reagents and enolates, underwent smooth hydroxymethylation showing the versatility of this process. A Wittig reaction was also carried out in high yield. [reaction: see text]     

Catalytic asymmetric mannich-type reactions activated by ZnF2 chiral diamine in aqueous media

Catalytic asymmetric Mannich-type reactions of an alpha-hydrazono ester with silicon enolates in aqueous media have been developed by using ZnF2 and chiral diamines as catalysts. In these reactions, both Zn2+ and a fluoride anion were necessary to achieve high yields and enantioselectivities, suggesting a double activation mechanism, in which Zn2+ activates the alpha-hydrazono ester and the fluoride anion simultaneously activates the silicon enolate. When chiral diamine ligands bearing methoxy-substituted aromatic rings were employed, the reactions in aqueous THF were markedly accelerated. Furthermore, the use of these diamines facilitated the asymmetric Mannich-type reactions in water without any organic cosolvents. It is noteworthy that either syn or anti adducts were stereospecifically obtained from (E)- or (Z)-silicon enolates, respectively. Interestingly, these reactions proceeded smoothly only in the presence of water. On the basis of several experimental results, it can be concluded that the reaction mechanism is likely to be a fluoride-catalyzed one, in which the ZnF2 chiral diamine complex is regenerated from the Me3SiF formed during the reaction.     

Recent Advances in the Chemistry of Heavier Group 14 Enolates

Recently heavier Group 14 enolates showed their importance and applicability in a broad range of chemical transformations. They were found to be key intermediates during the synthesis of photoinitiators, as well as during the formation of complex silicon frameworks. This Minireview presents general strategies towards the synthesis of heavier Group 14 enolates (HG 14 enolates). Structural properties, as well as their spectroscopic behavior are outlined. This study may aid future development in this research area.     

Iron‐ and Bismuth‐Catalyzed Asymmetric Mukaiyama Aldol Reactions in Aqueous Media

We have developed asymmetric Mukaiyama aldol reactions of silicon enolates with aldehydes catalyzed by chiral Fe^II and Bi^III complexes. Although previous reactions often required relatively harsh conditions, such as strictly anhydrous conditions, very low temperatures (?78 °C), etc., the reactions reported herein proceeded in the presence of water at 0 °C. To find appropriate chiral water‐compatible Lewis acids for the Mukaiyama aldol reaction, many Lewis acids were screened in combination with chiral bipyridine L1 , which had previously been found to be a suitable chiral ligand in aqueous media. Three types of chiral catalysts that consisted of a Fe^II or Bi^III metal salt, a chiral ligand ( L1 ), and an additive have been discovered and a wide variety of substrates (silicon enolates and aldehydes) reacted to afford the desired aldol products in high yields with high diastereo‐ and enantioselectivities through an appropriate selection of one of the three catalytic systems. Mechanistic studies elucidated the coordination environments around the Fe^II and Bi^III centers and the effect of additives on the chiral catalysis. Notably, both Brønsted acids and bases worked as efficient additives in the Fe^II‐catalyzed reactions. The assumed catalytic cycle and transition states indicated important roles of water in these efficient asymmetric Mukaiyama aldol reactions in aqueous media with the broadly applicable and versatile catalytic systems.     

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.     

An efficient synthesis of alkyl α-(hydroxymethyl)acrylates induced by DABCO in an aqueous medium

Alkyl α-(hydroxymethyl)acrylates are prepared in high yields on a synthetic scale by hydroxymethylation of the corresponding acrylates using 30% aqueous formaldehyde in THF or DME as solvent and DABCO as the catalyst.     

Catalytic asymmetric synthesis of alpha-amino phosphonates using enantioselective carbon-carbon bond-forming reactions

We have developed highly enantioselelctive reactions of silicon enolates with N-acyl-alpha-iminophosphonates leading to optically active alpha-amino phophonates. A copper (II)-diamine complex was shown to be effective in this reaction, and high levels of yield and selectivity were achieved. It is noteworthy that this reaction opens a way to various biologically important, optically active alpha-amino phosphonate derivatives.     

Iridium‐Catalyzed Enantioselective Allylic Substitution of Aliphatic Esters with Silyl Ketene Acetals as the Ester Enolates

Enantioselective allylic substitution with enolates derived from aliphatic esters under mild conditions remains challenging. Herein we report iridium‐catalyzed enantioselective allylation reactions of silyl ketene acetals, the silicon enolates of esters, to form products containing a quaternary carbon atom at the nucleophile moiety and a tertiary carbon atom at the electrophile moiety. Under relatively neutral conditions, the allylated aliphatic esters were obtained with excellent regioselectivity and enantioselectivity. These products were readily converted into primary alcohols, carboxylic acids, amides, isocyanates, and carbamates, as well as tetrahydrofuran and γ‐butyrolactone derivatives, without erosion of enantiomeric purity.     

Synthesis of 4(5)-hydroxymethylimidazoles by hydroxymethylation and decarboxylation of imidazole-4(5)-carboxylic acids

4(5)-Hydroxymethylimidazoles were prepared by hydroxymethylation and decarboxylation of imidazole-4(5)-carboxylic acid esters. The reaction was simply carried out with aqueous formaldehyde solution in the presence of base.     

Iridium-Catalyzed Enantioselective Allylic Substitution of Aliphatic Esters with Silyl Ketene Acetals as the Ester Enolates

Enantioselective allylic substitution with enolates derived from aliphatic esters under mild conditions remains challenging. Herein we report iridium-catalyzed enantioselective allylation reactions of silyl ketene acetals, the silicon enolates of esters, to form products containing a quaternary carbon atom at the nucleophile moiety and a tertiary carbon atom at the electrophile moiety. Under relatively neutral conditions, the allylated aliphatic esters were obtained with excellent regioselectivity and enantioselectivity. These products were readily converted into primary alcohols, carboxylic acids, amides, isocyanates, and carbamates, as well as tetrahydrofuran and γ-butyrolactone derivatives, without erosion of enantiomeric purity.     

Lewis base-promoted aldol reaction of dimethylsilyl enolates in aqueous dimethylformamide: use of calcium chloride as a Lewis base catalyst.

In the presence of CaCl2, dimethylsilyl (DMS) enolates smoothly reacted with aldehydes under mild conditions to give aldol adducts in good to high yields. The catalytic activities of various metal and tetrabutylammonium salts have revealed that CaCl2 works as a Lewis base catalyst to activate DMS enolates. The CaCl2-promoted reaction proceeded even in the presence of water or in pure water. This catalytic system was applicable to the aldol reaction with aqueous aldehydes such as formalin.     

三聚氰胺甲醛树脂合成—盐酸的催化作用及对产物稳定性的影响

三聚氰胺 (MA)在含有HCl的水溶液中与甲醛 (FA)进行羟甲基化反应。HCl与MA以等摩尔比结合 ,在反应过程中逐渐析出 ,至反应完毕仍保留半结合量。氢离子浓度对三聚氰胺甲醛树脂 (MF)溶液的稳定性有重要的影响     

Lewis acid-activated chiral leaving group: enantioselective electrophilic addition to prochiral olefins

A new strategy using a BINOL derivative as a chiral leaving group and Lewis acid has been developed for enantioselective alkylation of prochiral olefins. (R)-2,2'-Bis[2-(trimethylsilyl)ethoxymethyl]-1,1'-binaphthol is demonstrated to be an effective reagent for enantioselective hydroxymethylation of silyl enol ethers and trisubstituted alkenes. Electrophilic addition to prochiral olefins is accompanied by cleavage of an acetal that is dual activated by SnCl4 and the delta-effect of silicon through the S(N)2 substitution process. Enantioselective synthesis of cyclic terpenes is also described using this strategy.     

Catalytic silicon-mediated carbon-carbon bond-forming reactions of unactivated amides

In the presence of catalytic amounts of trialkylsilyl triflate and triethylamine, unactivated amides react with imines to afford the corresponding Mannich-type adducts in high yields with high anti selectivities. While silicon enolates have been widely used in organic synthesis for four decades, this is the first example of the catalytic use of the silicon species, to the best of our knowledge. Moreover, it is noteworthy that unactivated simple amides bearing α-protons that are less acidic than those of ketones and aldehydes can be successfully used in catalytic direct-type addition reactions. Finally, a preliminary trial of an asymmetric catalytic version was conducted and showed promising enantioselectivity of the desired product.     

Stereoselective aldol condensations via alkenyloxy dialkoxyboranes : mechanistic and stereochemical details

A detailed investigation of the enolization of ketones with ethylenechloroboronate ( ECB ) in the presence of a tertiary amine and the subsequent aldol condensations of these boron enolates was conducted. The enolization with ECB- DPEA system was found to be regioselective except for the case of butanone. The stereochemistry of the enolates derived from ethyl ketones was defined as Z on the basis of ¹H-NMR comparison to the Z enolates obtained by a stereodefined route. A mechanistic model for the enolization is proposed to explain the enolization selectivity. E enolates were found to be more reactive than the Z enolates. The product aldol stereochemistry ( syn ) was correlated to the enolate geometry via a chairlike transition state ( Z enolates ) or via a boatlike transition state ( E enolates ).     

Deprotonations,conjugate additions,and enolate trapping of oxime ethers and dimethylhydrazones using KDA : The effect of diisopropylamine on enolate trapping

Potassium diisopropylamide (KDA) has been used to efficiently generate the anions of oxime ethers and dimethylhydrazones. As a deprotonating agent, KDA is superior to BuLi and LDA. The corresponding cuprates are extremely oxygen sensitive, but undergo 1,4-addition with cyclohexenone, and the resulting potassium enolates can be trapped with aqueous buffer or ClSiMe₃. Attempted trapping with either Ac₂O or AcCl in the presence of diisopropylamine fails.     

Formaldehyde equilibria: Their effect on the kinetics of the reaction with phenol

The kinetics of the base catalyzed hydroxymethylation of phenol by aqueous formaldehyde are influenced strongly by the equilibria among the hydrated forms of formaldehyde, and among the hydrates and the alcoholic function of the products. Apparent peculiarities in the kinetics of the system and seemingly anomalous solvent effects are shown to be due to erroneous formulation of the previously accepted rate expression. The correct expression is: Rate = k[P_i^?] [F]m, where P_i^? is phenoxide ion, F is unreacted formaldehyde, and m is the fraction of formaldehyde in the form of monomeric hydrate. Formaldehyde tied up in equilibria as αω-poly(oxymethylene) diols, and hemiformals of the hydroxymethylphenols, constitutes a potential source of formaldehyde and is detected by the usual analytical procedures, but does not contribute to the rate of the hydroxymethylation reaction.     

Metal enolates of alpha-CF3 ketones: theoretical guideline, direct generation, and synthetic use

The difficulty as well as the significance of the direct generation of metal enolates of alpha-CF(3) ketones cannot be easily understood by chemists unfamiliar with F. In sharp contrast to the sunny side of non-F, hydrocarbon chemistry, F chemistry has long been overshadowed. Metal enolates of carbonyl compounds are synthetically important in C-C bond-forming reactions. However, the metal enolates of fluorinated carbonyl compounds have been severely limited to alpha-F metal enolates. Alpha-CF(3) metal enolates have generally been recognized as unstable and difficult to prepare because of the facile beta-M-F elimination. However, we have developed a direct generation and synthetic application of alpha-CF(3) metal enolates. Therefore, the present results regarding the direct generation and synthetic use of metal enolates of alpha-CF(3) ketones might be recognized as a real breakthrough for the general use of metal enolates in F chemistry.