A simple approach to separate a mixture of homopropargylic and allenic alcohols

A simple and practical approach to separate homopropargylic alcohol from allenic alcohol has been developed. It involves the formation of an insoluble silver acetylide species between silver nitrate and homopropargylic alcohol in aqueous acetone which can be separated from the allenic alcohol through a simple filtration. The homopropargylic alcohol can subsequently be recovered by hydrolysis with 1 N HCl. This protocol has been applied to the separation of a mixture of chiral homopropargylic and allenic alcohols in excellent yields with retention of absolute stereochemistry.     

Indium-mediated reaction of trialkylsilyl propargyl bromide with aldehydes: highly regioselective synthesis of allenic and homopropargylic alcohols

High regioselective preparation of either the allenic alcohols or homopropargylic alcohols using the indium-mediated reaction of trialkylsilyl propargyl bromides with various aldehydes has been accomplished. By just changing the silyl groups and the reaction conditions, both the allenic and homopropargylic alcohols can be obtained in high regioselectivities.     

镝促进下醛、酮与炔丙基溴及苯基炔丙基溴的高 选择性反应

在金属镝的促进下,醛、酮可与炔丙基溴反应,高选择性高产率地得到相应的高炔丙醇,没有发现连二烯醇的存在。当用苯基炔丙基溴代替炔丙基溴与醛、酮反应时,主要得到了相应的连二烯醇,而没有发现高炔丙醇的存在,由此提出了六元环过渡态的反应机理。     

金属单质锡促进的水相中醛的Barbier类型炔丙基化反应

报道了一种简单、 高效且快速的醛的炔丙基化反应体系. 使用廉价的金属单质锡粉, 在路易斯酸SnCl₂·2H₂O促进下, 实现了水相中醛羰基化合物的Barbier类型炔丙基化反应, 高收率、高区域选择性地得到单一的高炔丙基醇产物(收率99%). 该方法具有底物适用范围广、反应条件温和(30℃)、环境友好(以水为介质)及反应速度快(30 min内反应原料基本消失)等优点. 另外, 在使用肉桂醛为底物且将反应温度升至55℃时, 意外地得到了中等收率的新型高度对称的烯炔醚化合物.     

Rhodium(I)-catalyzed carbonyl allenylation versus propargylation via redox transmetalation across tetragonal tin(II) oxide

[reaction: see text] A reagent combination of beta-SnO and catalytic [Rh(COD)Cl](2) in THF-H(2)O promotes the reaction of propargyl bromides and aldehydes and directs the regioselectivity toward the formation of either allenic alcohols or homopropargylic alcohols. This highly regioselective either/or transformation proceeds via a transmetalation from rhodium to tin, in which metallotropic rearrangement between a propargylmetal and allenylmetal is arrested.     

Highly selective formation of propargyl- and allenyltrichlorosilanes and their regiospecific addition to various types of aldehydes: preparation of both allenic and homopropargylic alcohols

The highly selective preparation of propargyl- and allenyltrichlorosilanes via metal-catalyzed silylation of propargyl chloride has been developed. These trichlorosilyl nucleophiles were then shown to add to various types of aldehydes to afford the corresponding allenic and homopropargylic alcohols, respectively, in high yields with complete regiospecificity. Remarkably, these carbon–carbon bond-forming reactions simply proceeded in N,N-dimethylformamide (DMF) without using any metal catalysts.     

Copper(I)-catalyzed substitution of propargylic carbonates with diboron: selective synthesis of multisubstituted allenylboronates

A versatile synthetic method for the preparation of the allenylboronates, Cu(I)-catalyzed reaction of propargylic carbonates with a diboron, is described. A Cu(O-t-Bu)-Xantphos catalyst system was effective for the preparation of various allenylboron compounds, allenylboronates with different substitution patterns, those with functional groups, and an axially chiral one. The Lewis acid promoted stereoselective addition to aldehydes leading to homopropargylic alcohols showed the usefulness of the new allenylboronates.     

Iron(III)-catalyzed Prins-type cyclization using homopropargylic alcohol: a method for the synthesis of 2-alkyl-4-halo-5,6-dihydro-2H-pyrans

[reaction: see text] A new Prins-type cyclization between homopropargylic alcohol and aldehydes in the presence of FeX(3) to obtain 2-alkyl-4-halo-5,6-dihydro-2H-pyrans in good yield is described. Osmium-catalyzed cis dihydroxylation provided direct access to trans-2-alkyl-3-hydroxy-tetrahydro-pyran-4-ones. Anhydrous ferric halides are also shown to be excellent catalysts for the standard Prins cyclization using homoallylic alcohol. Isolation of an intermediate acetal provides substantiation of a proposed mechanism.     

Indium-mediated asymmetric Barbier-type propargylations: additions to aldehydes and ketones and mechanistic investigation of the organoindium reagents

We report a simple, efficient, and general method for the indium-mediated enantioselective propargylation of aromatic and aliphatic aldehydes under Barbier-type conditions in a one-pot synthesis affording the corresponding chiral alcohol products in very good yield (up to 90%) and enantiomeric excess (up to 95%). The extension of this methodology to ketones demonstrated the need for electrophilic ketones more reactive than acetophenone as the reaction would not proceed with just acetophenone. Using the Lewis acid indium triflate [In(OTf)(3)] induced regioselective formation of the corresponding homoallenic alcohol product from acetophenone. However, this methodology demonstrated excellent chemoselectivity in formation of only the corresponding secondary homopropargylic alcohol product in the presence of a ketone functionality. Investigation of the organoindium intermediates under our reaction conditions shows the formation of allenylindium species, and we suggest that these species contain an indium(III) center. In addition, we have observed the presence of a shiny, indium(0) nugget throughout the reaction, irrespective of the stoichiometry, indicating disproportionation of indium halide byproduct formed during the reaction.     

Highly Selective Synthesis of Acetylenic Alcohols Promoted by Metallic Dysprosium in the Presence of Mercuric Chloride

Promoted by metallic dysprosium, carbonyl compounds react smoothly with propargyl bromide to afford the corresponding homopropargylic alcohols in good to excellent yields without observation of allenic alcohols. In addition, this reaction is regioselective and chemoselective.     

Lewis acid-promoted cascade reaction of primary amine, 2-butynedioate,and propargylic alcohol: a convenient approach to 1,2-dihydropyridines and 1H-pyrrolo[3,4-b]pyridine-5,7(2H,6H)-diones

1,2-Dihydropyridine-5,6-dicarboxylates were efficiently constructed through a cascade reaction of primary amine, 2-butynedioate and propargylic alcohol in the presence of Lewis acid under mild conditions. As exceptional, 1H-pyrrolo[3,4-b]pyridine-5,7(2H,6H)-diones were approached when the primary amine was methylamine. Possible mechanism for the formation of 1,2-dihydropyridine skeleton is proposed. The process involves 1,3,4-pentatrien-1-amine as a key intermediate that formed in situ by trapping allenic carbocations with enamines.     

Lipase-mediated resolution of 4-TMS-3-butyn-2-ol and use of the mesylate derivatives as a precursor to a highly stereoselective chiral allenylindium reagent

[reaction: see text]. An improved procedure for the resolution of 4-trimethylsilyl-3-butyn-2-ol has been developed. The mesylate derivatives of the resolved alcohols have been found to undergo highly enantio-, regio-, and diastereoselective additions to aldehydes, leading to homopropargylic alcohol adducts.     

Gold-catalyzed tandem cycloisomerization-hydroalkoxylation of homopropargylic alcohols

The tandem cycloisomerization-hydroalkoxylation of various homopropargylic alcohols in the presence of an alcohol and a dual catalyst system, consisting of a gold precatalyst and a Br?nsted acid, provides an efficient route to tetrahydrofuranyl ethers under mild reaction conditions. The reaction can be carried out in various solvents, including alcohol, with both terminal and internal alkynes as the substrate.     

The silylalkyne-Prins cyclization: a novel synthesis of 4-iododihydropyrans

The silylated secondary homopropargylic alcohols undergo smooth coupling with aldehydes in the presence of molecular iodine under mild reaction conditions to produce 4-iododihydropyrans in good yields. This method is highly stereoselective, affording cis-dihydropyrans exclusively.     

Synthése d'alcools α-alléniques par réaction d'organochromiques propargyliques sur les aldéhydes et les cétones

Propargylic bromides can be condensed with aldehydes and ketones in the presence of Hiyama's reagent (2CrCl₃+LiAlH₄ in THF) leading to α-allenic alcohols, to homopropargylic alcohols or to the mixture of both of them. The selectivity (or specificity) of this reaction depends on the substitution of the propargylic bromide, on the structure of the ketone, and on the presence of HMPT in the reaction mixture. In many cases, the α-allenic alcohol has been specifically or very selectively obtained. The mechanism of the reaction and the influence of the various parameters are discussed.     

The synthesis of 4-halotetrahydropyrans and 4-halo-5,6-dihydro-2H-pyrans via the lewis acid promoted cyclization of acetals of homoallylic and homopropargylic alcohols

Ethyl vinyl ether, MEM chloride, and dihydropyran based acetals of homoallylic and homopropargylic alcohols cyclize in the presence of Lewis acids to give 4-halotetra-hydropyrans and 4-halo-5,6-dihydro-2H-pyrans, respectively.     

Preparation and use of enantioenriched allenylsilanes for the stereoselective synthesis of homopropargylic ethers

A convenient procedure for the synthesis of highly enantioenriched allenylsilanes by Johnson orthoester Claisen rearrangement of 1-silyl propargylic alcohols is described. Allenylsilanes are then used as carbon nucleophiles in three-component, Lewis acid mediated additions to in situ generated oxonium ions, resulting in enantioenriched homopropargylic ethers.     

(R)- and (S)-4-TIPS-3-butyn-2-ol. Useful precursors of chiral allenylzinc and indium reagents

A convenient route to the enantiomers of 4-TIPS-3-butyn-2-ol of >95% enantiomeric purity by reduction of the ynone precursor 4 with the Noyori N-tosyl-1,2-diphenylethylenediamineruthenium cymene catalyst is described. The mesylate derivative of the (S) enantiomer (1c) is converted in situ to an allenylzinc or indium reagent in the presence of a catalyst derived from Pd(OAc)2 and Ph3P and either Et2Zn or InI. A second in situ addition of these reagents to aldehydes leads to anti homopropargylic alcohol adducts. The additions proceed in generally high (60-90%) yield with modest to excellent diastereoselectivity and high enantioselectivity. Only slight mismatching (<5%) is observed with chiral alpha-methyl and alpha-silyloxy aldehydes. Additions to alpha-substituted enals are highly diastereoselective, while beta,beta-disubstituted enals afford ca. 2:1 mixtures of anti and syn adducts.     

The vinylogous aldol reaction of unsaturated esters and enolizable aldehydes using the novel Lewis acid aluminum tris(2,6-di-2-naphthylphenoxide)

The synthesis of the novel Lewis acid, aluminum tris(2,6-di-2-naphthylphenoxide) (ATNP), and its use in the vinylogous aldol reaction between methyl crotonate and enolizable aldehydes are described. ATNP is related to Yamamoto's Lewis acid, aluminum tris(2,6-diphenylphenoxide) (ATPH), but the 2-naphthyl groups more effectively block the α-position of aldehydes, enabling the selective enolization of crotonate esters in the presence of enolizable aldehydes. Vinylogous aldol reactions then proceed smoothly and in high yields with a variety of substrates.     

3-Bromopentadienylsilane: A new reagent for the introduction of a functional pentadienyl unit with fixed configuration

The (Z)-1-trimethylsilyl-3-bromopenta-2,4-diene 3 was prepared through a sequence involving the reductive silylation of butadiene, dibromocarbene addition on the resulting disilane 1, and thermolytic ring opening. With aldehydes, this new pentadienylsilane reacts exclusively via an S(E)' ' pathway. In the presence of an alcohol or a carbamate under Lewis acid activation, 3 yields, respectively, bromopentadienyl ethers or bromopentadienyl-protected amines.