Bis(1,1,3-trihydroperfluoropropyl)isocyanato Phosphite and Tris(1,1,3-trihydroperfluoropropyl) Phosphite in Reactions with Carbonyl Compounds

Abstract

Nucleophilicity of (I) in reactions with such carbonyl compounds as chloral, benzyl, ester and nitrile of benzoylformic acid is found to be notably reduced by the electronoaccepting perfluoropropyl groups. Unlike of dialkyl isocyanatophosphites (I) afford the cycloaddition products with ≡P-N- fragment (II) which being unable for the imide-amide rearrangement undergo dimerization into crystalline cyclodiphosphazanes (III) with pentacovalent phosphorus atoms.     

Electroinduced Addition of Fluoroalkyltrimethylsilanes to Carbonyl Compounds

Generation of a radical anion of a carbonyl compound in the presence of fluoroalkyltrimethylsilanes results in a chain reaction of addition to the carbonyl group with the generation of corresponding silyl ethers at a current efficiency of up to 7000%. A similar reaction is realized when zinc dust is used as the reductant.     

Novel Addition of Diphosphanes to Carbonyl Compounds

During our attempts to synthesize chiral bidentate bis(trifluoromethyl)phosphane containing ligands, we found a bis(trifluoromethyl)phosphanide induced formal insertion of acetone into tetrakis(trifluoromethyl)diphosphane.     

Enantioselective Alkynylzinc Addition to Carbonyl Compounds by Tf-based Sulfamide-amine Alcohol Catalysis

The new Tf‐based sulfamide‐amine alcohol 3a was found to be very effective in catalyzing the enantioselective alkynylzinc addition to both aromatic aldehydes and unactivated aromatic ketones without using another metal species under mild condition, providing up to 92% ee and 90% ee for aldehydes and ketones, respectively.     

Trimethylsilyl Cyanide Addition to Carbonyl Compounds Under Neutral Condition Catalyzed by Iodine

Reaction of trimethylsilyl cyanide with aliphatic or aromatic aldehydes and ketones in the presence of a catalytic amount of elemental iodine produced the corresponding cyanohydrin trimethylsilyl ethers in very short time and high yields.     

Catalytic Addition of Simple Alkenes to Carbonyl Compounds Using Group 10 Metals

Recent advances using nickel complexes in the activation of unactivated monosubstituted olefins for catalytic intermolecular carbon-carbon bond-forming reactions with carbonyl compounds, such as simple aldehydes, isocyanates, and conjugated aldehydes and ketones, are discussed. In these reactions, the olefins function as vinyl- and allylmetal equivalents, providing a new strategy for organic synthesis. Current limitations and the outlook for this new strategy are also discussed.     

Mechanism of Remote Conjugate Addition of Lithium Organocuprates to Polyconjugated Carbonyl Compounds

Regioselective reaction of a lithium organocuprate (R₂CuLi) and a polyconjugated carbonyl compound affords a remote‐conjugate‐addition product. This reaction proceeds particularly cleanly when the conjugation is terminated by a C? C triple bond. The reaction pathways and the origin of the regioselectivity of this class of transformations are explored with the aid of density functional calculations. The outline of the reaction pathway is as follows. An initially formed β‐cuprio(III) enolate intermediate undergoes smooth copper migration along the conjugated system. This process takes place faster than reductive elimination of intermediary σ/π‐allylcopper(III) species, since the latter reaction disrupts the conjugation in the substrate and hence is not preferred. The copper migration to the acetylenic terminal affords a σ/π‐allenylcopper(III) intermediate, which undergoes facile and selective C? C bond forming reductive elimination at the terminal carbon atom. The present mechanistic framework shows good agreement with some pertinent experimental data, including ¹³C NMR chemical shifts and kinetic isotope effects.     

Trimethylsilyl bis(Fluorosulfonyl)imide : An Efficient Catalyst for the Addition of Trimethylsilyl Cyanide to Carbonyl Compounds

In the presence of 1 mol% of trimethylsilyl bis(fluorosulfonyl)imide, trimethylsilyl cyanide adds efficiently to carbonyl compounds. The catalyst has been found to be more active than trimethylsilyl triflate for the above reaction.     

醛、酮结构对羰基亲核加成反应活性的影响

醛、酮分子中都含有活泼的羰基 ,亲核加成是醛酮最重要、最典型的反应之一。其反应历程为 :式中Ｒ为Ｈ或烃基 ,Ｎｕ为亲核试剂。这两种历程 ,决定反应速率的关键步骤均为Ｎｕ对羰基的进攻[1～ 3 ] 。因此 ,羰基化合物的结构以及Ｎｕ的性质对加成反应进行的难易程度均有影响。但在相同的条件下 ,同一亲核试剂对不同羰基化合物的加成反应 ,影响反应活性的因素就只有羰基化合物的结构了。国内有机化学教科书[3～ 7] 一般都是从两方面论述羰基反应活性的 :①电子因素 :当羰基碳上连有给电性基团 (如烷基、芳基等 )时 ,由于中心碳原子的电正性减…     

Nucleophilic Cyclopropanation Reaction with Bis(iodozincio)methane by 1,4‐Addition to α,β‐Unsaturated Carbonyl Compounds

Treatment of α,β‐unsaturated ketones with an electrophilic site at the γ‐position in the presence of trimethylsilyl cyanide with bis(iodozincio)methane afforded the (Z)‐silyl enol ether of the β‐cyclopropyl substituted ketone in good yields. The reaction proceeds by 1,4‐addition to form an enolate, and its sequential intramolecular nucleophilic attack to an adjacent electrophilic site. The reaction of γ‐ethoxycarbonyl‐α,β‐unsaturated ketone and bis(iodozincio)methane in the presence of trimethylsilyl cyanide afforded 1‐ethoxy‐1‐trimethylsiloxycyclopropane derivatives, which can be regarded as the homoenolate equivalent. Additionally, reaction of the obtained homoenolate equivalents with imines give 1‐(E)‐alkenyl‐2‐(1‐aminoalkyl)alkanols diastereoselectively.     

2-位氧化糖羰基转位反应的研究

α-甲基－D－葡萄糖苷的2－位羰基衍生物（简称为2－位氧化糖）,不仅在生物体糖代谢过程中起着关键作用,而且由于其自身多个手性中心及高活性羰基的存在,使之成为有机合成中的一种重要手性源,我们在前期的研究中发现,2－位氧化糖的羰基比其它位置氧化的葡萄糖苷具有更高的活性：在D2O中,2－位氧化糖的羰基100％以事形式存在,而3－位氧化糖则100％地以羰基形式存在,4－位氧化糖仅有25％以水合形式存在。因此,2－位氧化糖羰基反应活性的研究在不对称合成中有着重要意义。长期以来此方面的研究主要集中的2－位羰基及其邻位的烷基化,关于其氨基化反应鲜有报道。Tsuda等在合成Nojirimicin的过程中报道了羟胺与2－位氧化糖缩合成肟的反应,我们选择了芳胺与2－位氧化糖的反应进行研究,通过对邻苯二胺与2－位氧化糖反应所形成中间产物的^1H NMR谱变化的跟踪,并选用其它芳胺进行验证,发现芳胺类化合物在与2－位氧化糖反应时,并未生成C＝N双键,而是生成了羰基转化到3－位的加成产物。2－位氧化糖芳胺亲核加成引起羰基转位反应式如Scheme 1所示。     

Michael Addition of Thiols to á,(a)-Unsaturated Carbonyl Compounds Catalyzed by Bifunctional Organocatalysts:Asymmetric Michael Addition and Asymmetric Protonation

Recently the hydrogen-bond activated reactions have attracted much attention.1 Takemoto2 reported a highly enantioselective Michael addition of manolate to nitroolefins catalyzed by a bifunctional organocatalyst with tertiary amine and thiourea moiety. As we known,stereoselective conjugate additions of thiols are interesting due to the standpoint of biological and synthetic importance, however, only very limited good results have been obtained except for the works of Shibasaki3, Kanemasa4 and Deng5 et al.In this letter, we report an efficient catalytic asymmetric Michael reactions of thiols to a,a-unsaturated carbonyl compounds promoted by bifunctional organocatalysts. A series of organocatalysts with chiral amine and thiourea structures were designed and synthesized and have been successfully applied in the conjugated additions of thiols to a,a-unsaturated imides and enones.The reactions got quantitative yields and the ee values were up to 84%. It is noteworthy that the a-asymmetric protonation (up to 43% ee) also could be achieved.The Michael addition between aromatic thiols and a,a-unsaturated carbonyl compounds isdescribed as follows:Works to further increase the enantioselectivity is under investigation in our laboratory.     

Hitting a Soft Drug with a Hard Nucleophile: Preparation of Esmolol's Metabolite by Treatment with Bis(tributyltin) Oxide

A facile method for the production of esmolol's metabolite in high purity is described. Bis(tributyltin) oxide is used to disrupt esmolol's ester linkage, and hydrolysis is completed by addition of water, which also allows the inorganic side products to be conveniently extracted into ether. Evaporation of the aqueous phase and trituration with ethyl acetate provides the carboxylic acid–amine internal salt as a white, free-flowing powder.     

A Nucleophilic Addition of Acetone Enolate to ( E)-Alkyloxindolylideneacetates

The reaction of (E)-(2-oxo-1,2-dihydroindol-3-ylidene)acetic acid esters with dry acetone at 70°C in presence of aluminum oxide as a catalyst led to the formation of an addition product as a mixture of two isomers. When the same reaction was carried out in presence of morpholine as a base, the unexpected spiro-product was obtained beside the two isomers. Methylation of the latter with methyl iodide in acetone in presence of anhydrous potassium carbonate yielded the corresponding methylated products, whereas methylation of the starting material by the same procedure gave an N-methylated product and the unexpected dispiro-compound. The reaction mechanisms are considered and the structural assignments of the new compounds are based on the chemical and spectroscopic evidences. The structure of the dispiro-product was derived by X-ray analysis.     

Enantioselective Addition of Organometallic Reagents to Carbonyl Compounds: Chirality Transfer,Multiplication, and Amplification

Nucleophilic addition of organometallic reagents to carbonyl substrates constitutes one of the most fundamental operations in organic synthesis. Modification of the organometallic compounds by chiral, nonracemic auxiliaries offers a general opportunity to create optically active alcohols, and the catalytic version in particular provides maximum synthetic efficiency. The use of organozinc chemistry, unlike conventional organolithium or -magnesium chemistry, has realized an ideal catalytic enantioselective alkylation of aldehydes leading to a diverse array of secondary alcohols of high optical purity. A combination of dialkylzinc compounds and certain sterically constrained β-dialkylamino alcohols, such as (–)-3-exo-dimethylaminoiso- borneol [(–)-DAIB], as chiral inducers affords the best result (up to 99% ee). The alkyl transfer reaction occurs via a dinuclear Zn complex containing a chiral amino alkoxide, an aldehyde ligand, and three alkyl groups. The chiral multiplication method exhibits enormous chiral amplification: a high level of enantioselection (up to 98%) is attainable by use of DAIB in 14% ee. This unusual nonlinear effect is a result of a marked difference in chemical properties of the diastereomeric (homochiral and heterochiral) dinuclear complexes formed from the dialkylzinc and the DAIB auxiliary. This phenomenon may be the beginning of a new generation of enantioselective organic reactions.     

Addition Reaction Between Trimethyl Phosphite and Dibenzoylacetylene in the Presence of SH- or NH-Acids

The reactive 1:1 intermediate produced in the addition reaction between trimethyl-phosphite and dibenzoylacetylene was trapped by SH- or NH-acids such as 4-nitroimidazole, 4-methyl-5-nitroimidazole, succinimide, or mercaptoacetic acid to produce 2-substituted 1,4-diphenylbutane-1,4-diones.