Cp2TiCl2-Catalyzed hydroalkylation of α-olefins with ButBr—Et3Al

The reactions of olefins with alkyl halides and Et₃Al in the presence of catalytic amounts of Cp₂TiCl₂ were studied. Unbranched -olefins of the aliphatic series underwent hydroalkylation under the action of tert-butyl bromide to form 2,3-dimethylalkanes.     

Direct Zinc(II)-Catalyzed Enantioconvergent Additions of Terminal Alkynes to α-Keto Esters

The addition of terminal alkynes to racemic β-stereogenic α-keto esters was achieved in high levels of stereoselectivity, affording versatile tertiary propargylic alcohols containing two stereocenters. This environmentally benign enantioconvergent reaction proceeds with perfect atom economy, requires no solvent, and is catalyzed by a non-toxic zinc salt. The alkyne moiety can be leveraged in downstream transformations including hydrogenation to the corresponding saturated tertiary alcohol, which represents the product of a formal enantioconvergent aliphatic nucleophile addition.     

One-Pot Approach to the Conversion of Alcohols into α-Iodo-α,β-unsaturated Esters

(Carboethoxymethylene)triphenylphosphorane 1 can undergo the tandem reaction of iodination–oxidation–Wittig reaction with alcohol in the presence of N-iodosuccinimide (NIS) and manganese dioxide. The reaction constitutes a stereoselective one-pot procedure for the preparation of Z-configured α-iodo-α,β-unsaturated esters in good to excellent yield.     

Direct Light-Enabled Access to α-Boryl Radicals: Application in the Stereodivergent Synthesis of Allyl Boronic Esters**

Operationally simple strategies to assemble boron containing organic frameworks are highly enabling in organic synthesis. While conventional retrosynthetic logic has engendered many platforms focusing on the direct formation of C−B bonds, α-boryl radicals have recently reemerged as versatile open-shell alternatives to access organoborons via adjacent C−C bond formation. Direct light-enabled α-activation is currently contingent on photo- or transition metal-catalysis activation to efficiently generate radical species. Here, we disclose a facile activation of α-halo boronic esters using only visible light and a simple Lewis base to enable homolytic scission. Intermolecular addition to styrenes facilitates the rapid construction of highly versatile E-allylic boronic esters. The simplicity of activation permits the strategic merger of this construct with selective energy transfer catalysis to enable the complimentary stereodivergent synthesis of Z-allylic boronic esters.     

A Substrate-Driven Approach to Determine Reactivities of α,β-Unsaturated Carboxylic Esters Towards Asymmetric Bioreduction

The degree of C?C bond activation in the asymmetric bioreduction of α,β-unsaturated carboxylic esters by ene-reductases was studied, and general recommendations to render these "borderline-substrates" more reactive towards enzymatic reduction are proposed. The concept of "supported substrate activation" was developed. In general, an additional α-halogenated substituent proved to be beneficial for enzymatic activity, whereas β-alkyl or β-aryl substituents were detrimental for the reactivity of nonhalogenated substrates, and α-cyano groups showed little effect. The alcohol moiety of the ester functionality was found to have a strong influence on the reaction rate. Overall, activities were determined by both steric and electronic effects.     

Is the trinuclear complex the true reducing species in the Cp2TiCl2/Mn- and Cp2TiCl2/Zn-promoted pinacol coupling?

Through a combination of kinetic, voltammetric and product analysis, it has been found that a common Ti^III species obtained from the metal reduction of Cp₂TiCl₂ is involved in the electron transfer to benzaldehyde. A common species in the pinacol dimerization step was also demonstrated. In neither of the two steps is it necessary to invoke trinuclear complexes as previously proposed.     

An Improved Procedure for Hydrosilation of α,β-Unsaturated Esters and an Extension to Conjugated Diene Esters

Treatment of α,β-unsaturated esters with triethylsilane in benzene in the presence of a catalytic amount of tris(triphenylphosphine)rhodium chloride at room temperature followed by chromatography on silica gel gave rise to the corresponding saturated esters. Under similar conditions, fully conjugated diene esters were reduced to the dihydrolevel to give β,γ- or γ,δ-unsaturated esters depending upon the substitution pattern of the starting substrate.     

Manganese(I)-Catalyzed Regioselective C−H Allenylation: Direct Access to 2-Allenylindoles

A Mn^I-catalyzed regioselective C−H allenylation is reported that allows a broad range of 2-allenylindoles to be synthesized regioselectively on a gram scale under simple conditions. Notably, a highly efficient chirality transfer was observed (up to 93 % ee) in this transformation. This procedure was further found to allow, for the first time, the direct preparation of ketones by Mn^I-catalyzed C−H activation. Mechanistic investigations revealed that the precoordination of the oxygen atom to the manganese center as well as the congested tertiary carbon atom in the propargylic carbonates play a crucial role.     

A Convenient Method for the Synthesis of α-Functionalized Chlorophosphonic Esters

α-Functionalized chlorophosphonic monoesters were easily prepared by a selective chlorination of the corresponding phosphonic diesters with phosphorus oxychloride.     

A Convenient General Access to α-Sulfenylated Acetophenones and Alkanones

Friedel-Crafts acylation of arenes with methylthio- (1) or phenylthio-acetyl chloride (2) provides ready access to α-methylthio- or α-phenylthio-substituted acetophenones. The acyl chlorides 1 and 2 reacted also with organoaluminum reagents to give α-sulfenylated alkanones.     

Gold(I)-Catalyzed and PTSA-Promoted Cycloisomerization of Ynamides to Access Pyrrole Substituted α,β-Unsaturated Ketones**

Substituted pyrroles are prevalent aromatic ring systems encountered in numerous natural products and bioactive molecules. Herein, a novel ynamide scaffold has been designed, synthesized and subsequently applied to an unprecedented gold-catalyzed and para-toluenesulfonic acid (PTSA)-assisted cascade cycloisomerization reaction for the synthesis of β-pyrrole substituted α,β-unsaturated ketones. Notably, the reaction is stereoselective, offering E-isomer as major product with low to moderate yield.     

A New Method for the Reductive Cleavage of S-S Bond by the System of Cp2TiCl2/i-BuMgBr/THF and its Application in Synthesis of α-Alkylthio Carbonyl Compounds

The reduction of disulfides by Cp₂TiCI₂/i-BuMgBr/THF led to nucleophilic sulfides [Cp₂TiSR]. This species reacted with α-broroo carbonyl compounds to give α-alkylthio carbonyl compounds in high yields.     

A Novel Approach to Synthesis of α，β－Unsaturated Ketones

A new approach to the synthesis of α，β-unsaturated ketones from 1,2,3-trimethyl benzimidazolium salt via the condensation reaction with aldehydes followed by the addition reaction of Grignard reagents with quaternary C=N bond was provided.     

One-pot Approach to the Conversion of Alcohols into α-Halo-α,β-unsaturated Esters

α-Halo-α, β-unsaturated esters are important intermediates in organic synthesis. For example, they are used for α-amino acid preparation1 and vinylogous Darzen reactions2, as a versatile fluorinated building block, they are also used for the preparati…     

A facile method for the synthesis of enantiopure α-unsubstituted β-hydroxy esters

One-pot deacylation–debromination reactions involving the transesterification of the initial chiral α-bromo-β-hydroxy thioimide aldol adducts and subsequent Al–Hg mediated reductive cleavage of the C–Br bond allow for a facile synthesis of enantiopure β-hydroxy esters.     

A mild, efficient method for the oxidation of α-diazo-β-hydroxyesters to α-diazo-β-ketoesters

A wide variety of α-diazo-β-ketoesters can be prepared in good overall yields via a two-step sequence involving addition of ethyl lithiodiazoacetate to aliphatic, aromatic, and conjugated aldehydes followed by mild oxidation with the Dess-Martin periodinane.     

Stereoselective allylation of α-hydroxy aldimines and its application to the formal synthesis of (−)-β-conhydrine

Stereoselective allylation of N-p-methoxyphenyl (PMP)-substituted α-hydroxy aldimines is described. Several Lewis acids (BF₃·OEt₂, SnCl₄, TiCl₄, ZnCl₂, and MgBr₂·OEt₂) were employed to mediate the allylation reactions. The addition of the allyl group generates a new stereocenter and affords the syn vicinal amino alcohol. Formal synthesis of (?)-β-conhydrine (1) was accomplished via syn-selective allyl addition to N-PMP-substituted α-hydroxy aldimine.     

Organoselenium-mediated reduction of α,β-epoxy ketones to β-hydroxy ketones: A new access to inter- and intramolecular aldols

The organoselenium-mediated reduction of α,β-epoxy ketones has been demonstrated to be a promising entry to a variety of cyclic and acyclic aldols.     

Access to the syntheses of sydnonyl-substituted α,β-unsaturated ketones and 1,3-dihydro-indol-2-ones by modified Knoevenagel reaction

A convenient method for the preparation of sydnonyl-substituted α, β-unsaturated ketones, based on Knoevenagel condensation, is presented. Although well known, this reaction has never been utilized in the condensation involving sydnone derivatives. Thus, 3-aryl-4-formylsydnones (1) are reacted with active methylene compounds such as acetylacetone (2a), ethyl acetoacetate (2b), diethyl malonate (2c), malononitrile (4a), ethyl cyanoacetate (4b) and cyanoacetamide (4c) by modified Knoevenagel condensation to afford multifunctional derivatives. Also, sydnonyl-substituted 1,3-dihydro-indol-2-one derivatives 10 were synthesized successfully by condensing 3-aryl-4-formylsydnones (1) with oxindoles 9.     

A highly stereoselective conversion of α,β-epoxy esters to α-hydroxy esters. An efficient route to optically active α-hydroxyesters

α,β-Epoxy esters were cleanly converted to α-hydroxy esters with retention of the configurations at the α-carbon atoms via MgI₂-promoted regioselective oxirane ring-opening followed by tributyltin hydride-reduction.