Organocerium Reagents Research Articles

Highly stereoselective titanium-mediated addition of organocerium reagents to β-keto amides: an efficient synthesis of stereodefined β-hydroxy amides having a tertiary alcoholic fragment

A highly efficient and stereoselective protocol for the TiCl 4-mediated addition of organocerium reagents to β-keto amides is now available. The method allows the introduction of a large variety of carbon frameworks, including primary, secondary and tertiary alkyl chains, as well as aromatic, alkynylic and benzylic moieties, in high yields and with high stereoselection.

Highly Stereoselective and Efficient Addition of Organocerium Reagents to syn-β-Alkyl-β-hydroxy-α-methyl Ketones by Way of Their Titanium Alkoxides − Synthesis of Complex 1,3-Diol Units with Three Stereodefined Centres

A highly efficient and stereoselective technique for additions to syn-β-alkyl-β-hydroxy-α-methyl ketones is now available. The methodology is based on the conversion of the starting material into a trichlorotitanium alkoxide derivative, which is able to assume a stable cyclic arrangement exhibiting high stereofacial discrimination towards nucleophilic alkyl transfer by an appropriate organometallic species. The use of Grignard reagents has serious limitations; in fact, highly hindered and basic reagents do not work well with enolizable substrates. Organocerium compounds can obviate these drawbacks, since side processes such as enolization or interaction with titanium(IV) are almost completely suppressed. The method permits the introduction of a large variety of carbon systems, including primary, secondary and tertiary alkyl chains, as well as aromatic, alkynyl and benzylic moieties, in high yields and with good stereoselectivities.

Nucleophilic addition of organocerium reagents to?-alkoxy hydrazones: A new type of elimination reaction to?-hydroxynitriles

We studied the nucleophilic addition of organocerium reagents to α-alkoxy hydrazones. The results depend upon the organocerium reagents, the nature of protection for the hydroxy group, and the solvents used. Contrary to Grignard reagents, organocerium reagents derived from Grignard reagents effectively add to α-alkoxy hydrazones. In addition, a new type of elimination reaction of α-alkoxy hydrazones to the corresponding nitriles by methyl chloroformate was found. This methodology is an efficient and potentially practical synthetic route to β-hydroxy amines. © 2000 John Wiley & Sons, Inc. Heteroatom Chem 11:65–72, 2000

Synthesis of Phosphane Oxides and Phosphonates by Cerium-Mediated Addition of Organolithium Compounds to Chloro-Phosphorus Compounds

The addition of organocerium reagents 2a–g to phosphinoyl chloride 1a or chlorophosphates 1b leads to the synthesis of phosphane oxides 3aa–ag and phosphonates 3bb, be in good to high yield. The reaction can be extended to cerium enolates 4 (of ketones) and 6 (of nitriles) except when a benzyl group bound to the carbonyl moiety should be metallated. The latter reaction is the first reported synthesis of β-oxophosphane oxides by a simple reaction between enolates and a phosphorus(V) halide.

Synthesis of Phosphane Oxides and Phosphonates by Cerium-Mediated Addition of Organolithium Compounds to Chloro-Phosphorus Compounds

The addition of organocerium reagents 2a–g to phosphinoyl chloride 1a or chlorophosphates 1b leads to the synthesis of phosphane oxides 3aa–ag and phosphonates 3bb, be in good to high yield. The reaction can be extended to cerium enolates 4 (of ketones) and 6 (of nitriles) except when a benzyl group bound to the carbonyl moiety should be metallated. The latter reaction is the first reported synthesis of β-oxophosphane oxides by a simple reaction between enolates and a phosphorus(V) halide.

ChemInform Abstract: Highly Diastereoselective Synthesis of 1,2‐Amino Alcohols via Nucleophilic Addition of Organocerium Reagents to 4‐ and 5‐Oxazolidinonecarbaldehydes.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Highly diastereoselective synthesis of 1,2-amino alcohols via nucleophilic addition of organocerium reagents to 4- and 5-oxazolidinonecarbaldehydes

The reaction of chiral, non-racemic 4- and 5-oxazolidinonecarbaldehydes, 6 and 13, with organocerium reagents proceeds efficiently with good to excellent diastereoselectivity to give syn and anti alcohols, respectively. A model to explain the observed diastereoselectivity of the reaction of 6 and 13 is provided. The utility of this method for the synthesis of amino alcohols is exemplified by the synthesis of C-18-D-ribo-phytosphingosine from the anti alcohol 14f.Key words: oxazolidinonecarbaldehydes, organocerium, diastereoselective, amino alcohols, C-18-ribo-phytospingosine.

Total Synthesis of Roseophilin

The first total synthesis of the antitumor agent roseophilin 1 is reported. Its intricate macrotricyclic core 2 is obtained by means of a new palladium-catalyzed manifold for the formation of ansa-bridged pyrroles which proceeds via vinyl oxirane 8 and allyl lactone 11 as key intermediates. After conversion of the latter into pyrrolophane 14, a base-induced elimination of the sulfone group followed by the Michael addition of a zincate onto the resulting enone 18 installs the isopropyl substituent in a stereoselective manner. The pyrrolylfuran side chain 3 of roseophilin is prepared from 4-methoxy-2(5H)-furanone (24) and methyl 4-chloropyrrole-2-carboxylate (26) as the starting materials. The appropriate building blocks 25a and 28 derived thereof are combined via a sequence comprising a directed metal−halogen exchange reaction, transmetalation of the resulting lithiopyrrole to the corresponding organozinc compound, a palladium-catalyzed cross coupling of the latter, and a subsequent acid-catalyzed closure of the resulting ketone 29 leading to the furan entity of the target. The triisopropylsilyl-protected side chain 3b is first deprotonated with n-BuLi and then transmetalated with CeCl3 to give a highly nucleophilic organocerium reagent, which readily attacks the sterically hindered 2-(trimethylsilyl)ethoxymethyl-protected keto pyrrole 2c. Deprotection and final dehydration of the tertiary alcohol derivative 30 thus obtained leads to the intact azafulvene chromophore of the natural product and completes our total synthesis of this alkaloid.

Diastereoselective Synthesis of γ-Hydroxy-β-amino Alcohols and (2S,3S)-β-Hydroxyleucine from Chiral d-(N,N-Dibenzylamino)serine (TBDMS) Aldehyde

Title serine deriv. I (TBDMS = tert-butyldimethylsilyl; Bn = benzyl) was synthesized from D-serine in excellent overall yield. The reactions of I with Grignard and organocerium reagents were highly stereoselective (Felkin model) to give gamma -hydroxy-beta -amino alcs. II (R = CHMe2, Me, Ph, Bu) in good yield. Transformation of II (R = CHMe2) into (2S,3S)-beta -hydroxyleucine (III) is also reported. [on SciFinder (R)]

Highly diastereoselective synthesis of 1,2-amino alcohols via nucleophilic addition of organocerium reagents to 4- and 5-oxazolidinonecarbaldehydes

Highly diastereoselective synthesis of 1,2-amino alcohols via nucleophilic addition of organocerium reagents to 4- and 5-oxazolidinonecarbaldehydes

Ligand Effects in Diastereoselective Additions of Organocerium Reagents to Carbonyl Substrates

Ligand Effects in Diastereoselective Additions of Organocerium Reagents to Carbonyl Substrates

Bicyclo[3.3.1]nonanes as Synthetic Intermediates. XXIII.1 A Breakthrough by Lanthanoid Mediation in Nucleophilic Addition of Carbanions to the Inert “Fork Head” Carbonyl in Bicyclo[3.3.1]nonan-3-ones

Owing to the “backside steric hindrance”, the ‘fork head ketone’ (C-3 ketone) in bicyclo[3.3.1]nonan-3-ones is quite inactive against a nucleophilic attack of several kinds of organometallic reagents. Organocerium reagents and samarium iodide / organohalides turned out to react with the fork head ketone to afford the corresponding adducts efficiently.

Synthesis of a novel antiinflammatory agent, BTS 71321, singly labelled with carbon‐14 in two positions

The synthesis of the antiinflammatory compound, BTS 71321, singly labelled with carbon-14 in two positions, is described. Labelling of the imidazole ring of the compound was achieved using [2-14C]imidazole, prepared from potassium [14C]cyanide via potassium [14C]thiocyanate, whereas labelling of the tertiary carbon atom in the chain was effected by means of procedure starting from barium [14C]carbonate and involving an organocerium reagent. © John Wiley & Sons, Ltd.

Reaction of SilyLketenes with Carbanions: Simple Preparation of .ALPHA.-SilyLketones Using Organocerium Reagents.

Preparation of α-silylketones 1 by the reaction of three kinds of silylketenes 3a-c with various organometallic reagents 4 was studied. Although the use of n-BuLi, MeMgBr, Me2CuLi, Et3Al, and Et2Zn resulted in complicated reactions, organocerium reagents 4 (M=CeCl2) added selectively to the carbonyl carbon of 3 to generate enolate anions A, which were treated with aqueous NH4Cl or alkyl halides 5 to give 1. Seventeen α-silylketones 1a-q were prepared in 31-99% yields from three components, 3, alkyl- or arylcerium reagents 4, and proton or alkyl halides 5. This method was applied to a regiocontrolled preparation of two isomeric α-silylketones 1r, s.

ChemInform Abstract: Diastereoselectivity in the Addition of Organocerium Reagents to 4‐ and 5‐Oxazolidonecarbaldehydes: Synthesis of syn‐ and anti‐Alcohols.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: A Stereoselective Synthesis of (E)‐α,β‐Unsaturated Ketones Involving the Reactions of Organocerium Reagents with Secondary β‐ Enamino Ketones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform Abstract: Excellent Chiral Introduction by Diene Iron‐Tricarbonyl Moiety. Part 3. Asymmetric Synthesis of Hydroxyethylidene Dipeptide Isostere Using a Diastereoselective 1,2‐Nucleophilic Addition of Organocerium Reagents into a 1‐Azatriene Fe(CO)3 Complex.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Diastereoselectivity in the addition of organocerium reagents to 4- and 5-oxazolidonecarbaldehydes: Synthesis of syn- and anti-alcohols

Chiral non-racemic 4- and 5-oxazolidonecarbaldehydes, typified by 2 and 7, react highly diastereoselectively with organocerium reagents to give moderate to good yields of syn- and anti-alcohols, respectively. Rationalizations for the observed diastereoselectivities are presented. The synthetic potential of this method is exemplified by the synthesis of C-18-D- ribo-phytosphingosine which was obtained as its tetraacetate.

A Stereoselective Synthesis of (E)‐α, β‐Unsaturated Ketones Involving the Reactions of Organocerium Reagents with Secondary β‐Enamino Ketones

AbstractStereoselective construction of trisubstituted alkenes has wide applicability to the synthesis of many natural products Specifically, β‐disubstituted enones are important functionalized trisubstituted alkene targets. The reaction of organocerium reagents with secondary β‐enamino ketones affords β=disubsituted α,β‐unsaturated ketones in fairly good yields. This process shows considerable stereoselectivity, and α,β‐unsaturated ketones of (E) configuration are predominantly observed. Organolithium‐derived cerium reagents display better stereoselectivity than organomagnesium‐based ones. The mechanism of the reaction varies with nitrogen substitution: N‐phenyl groups give 1,2‐addition products, whereas substitution products are observed with N‐alkyl groups. When organocerium reagents were used with β‐enamino ketones bearing secondary alkyl groups at the nitrogen atom, a lack of reactivity was observed.

Enantioselective addition of tris(TADDOL) organocerium reagents to aldehydes

A significant improvement in enantioselectivity (up to 92% ee) was achieved in butyl additions to a range of aldehydes with a novel tris(TADDOL) organocerium reagent.