Homoallylic Alcohols Research Articles

Total Synthesis of the Purported Structure of Branched Resin Glycosides Merremoside G and H2.

The first total synthesis of the purported structure of branched resin glycosides merremoside G and H2 is accomplished. A signature step is represented by the sequential transition-metal-catalyzed coupling of stable trisaccharide homoallylic alcohol and monosaccharide alkoxyallene to afford the pentasaccharide skeleton. This de novo strategy is conducted under mild conditions with no need of preactivation. In addition, it allows for efficient preparation of the target compounds in combination with late-stage functionalization.

Photoredox chromium and cobalt dual catalysis for carbonyl allylation with butadiene via allyl radical intermediates

The allylation of aldehydes with dienes was achieved using cobalt and chromium catalysts through a metal-hydride hydrogen atom transfer (MHAT) pathway. The novel reaction resulted in the formation of various homo-allyl alcohols with excellent diastereoselectivity.

Electrochemical allylation of aldehydes and ketones with allylic alcohols

We disclose herein an electrochemical allylation of unactivated aldehydes and ketones with allylic alcohols. Various homoallylic alcohols can be obtained by treatment of aldehydes/ketones with allyl alcohols in a simple undivided cell.

Pd(II)-catalyzed hydroarylations/hydroalkenylations of terminal alkynes: regioselective synthesis of allylic, homoallylic, and 1,3-diene systems.

A Pd-catalyzed regioselective hydroarylation of terminal alkynes containing a heteroatom has been developed via carbopalladation for the synthesis of allylic ethers, amines, and homoallylic alcohols. Moreover, hydroalkenylation of alkynes produces a variety of stereodefined 1,4-dienes with high regioselectivity. The important features of the present protocol are that it is highly regioselective, operationally rapid, and scalable with a huge substrate scope using only 3 mol% of PdCl2(PPh3)2 catalyst in the presence of a mild base KOAc.

Ni-catalyzed regioselective C–C bond formation of 1,1-disubstituted allenes with aldehydes

A regio- and stereoselective coupling process between allenes and aldehydes has been developed to obtain a linear homoallylic secondary alcohols by photoredox/Ni dual catalysis.

Cobalt-catalyzed three-component assembly of aromatic oximes with substituted dienes and formaldehyde.

A cobalt-catalyzed three-component assembly of substituted aryl oximes with dienes and formaldehyde via C-H bond activation is described. This protocol affords highly regio- and chemoselective substituted homoallylic alcohols with moderate-to-excellent yields. The scope of this protocol has been extensively explored with various substituted aryl ketoximes and aldoximes. Butadiene and internally substituted dienes are also well compatible for this transformation. A plausible reaction mechanism is proposed to account for the present reaction and is supported by deuterium labeling studies.

Photochemical carboborylation and three-component difunctionalization of α,β-unsaturated ketones with boronic acids via tosylhydrazones.

The reactions of cyclic α,β-unsaturated N-tosylhydrazones and alkylboronic acids promoted by 370-390 nm light in the presence of a base give rise to allylic boronic acids that can be trapped as the corresponding pinacolboronates by treatment with pinacol. This reaction features wide scope regarding both coupling partners and functional group tolerance, allowing for the incorporation of a variety of natural product-derived fragments. The allylic boronic acids can be also reacted in a one-pot process with aldehydes, to produce homoallylic alcohols with very high diastereoselectivity. A three-component one-pot procedure has been developed revealing that the methodology is a powerful tool for the generation of structural diversity that is accomplished by incorporation of an ample variety of each of the three elements. Moreover, from a synthetic perspective, in the reaction, the formation of two C-C bonds, at the carbonyl and the β positions of a α,β-unsaturated carbonyl, has been achieved in the three-component reaction.

Total Synthesis of (+)-Peniciketal B.

An efficient synthesis of (+)-peniciketal B has been accomplished in 15 steps from the commercially available materials atraric acid, acryloyl chloride, and (+)-homoallylic alcohol. A convergent synthetic approach that is quite concise for constructing either "hemisphere" of (+)-peniciketal B with a common intermediate is employed that relies on a cascade intermolecular FeCl3-mediated "inner sphere" Michael-type reaction/double cyclization of an α,β-unsaturated ketone and substituted phenol to build the benzo-fused 2,8-dioxabicyclo[3.3.1]nonane with excellent diastereoselectivity. The generality of the transformation was also demonstrated by the broad scope of substrates that would be potential candidates for natural product synthesis and medicinal chemistry. Benzannulated [6,6]spiroketal was installed by a late-stage acid-catalyzed spiroketalization.

Asymmetric and Regiodivergent Synthesis of Silyl-Containing Homoallylic Alcohols Using Cu Catalysis

Asymmetric and Regiodivergent Synthesis of Silyl-Containing Homoallylic Alcohols Using Cu Catalysis

Stereoselective Construction of β-chiral Homoallyl Functionalities by Substrate- and Reagent-Controlled Iterative 1,2-Metallate Rearrangements.

Homoallylic alcohols possessing chiral β-centers are considered highly valuable in the synthesis of polyketide-based natural products. Therefore, there is a significant demand for new methods that allow for their stereoselective access. In pursuit of this objective, we have successfully combined our substrate-controlled protocol of Hoppe-Matteson-Aggarwal chemistry with iterative 1,2-metallate rearrangements. Notably, this approach has proven effective in introducing not only primary alcohols but also other functional groups such as alkynes and protected amines.

Nickel-Catalyzed Reductive Allylation of Aldehydes with Allylic Alcohols in the Presence of CO2.

CO2-assisted and Ni-catalyzed direct reductive allylation of aldehydes utilizing allylic alcohols as allylic precursor has been reported. Various homoallyl alcohols could be synthesized in excellent yield with enhanced regioselectivity and stereoselectivity for alkyl- and aryl-substituted aldehydes under mild conditions. For different substrates, proper collocation of the catalytic precursor and ligand is crucial. Preliminary mechanistic studies supported the reaction pathway through a sequential allyl hydrocarbonate formation/allylnickelation/coordination insertion process by the Ni(I)/Ni(III) catalytic cycle, which has been proven by cyclic voltammetry analysis.

Nickel-Catalyzed Borylative Coupling: An Access to Functionalized Chiral Homoallylic Alcohols

Nickel-Catalyzed Borylative Coupling: An Access to Functionalized Chiral Homoallylic Alcohols

Cu‐Catalyzed Enantioselective Reductive Coupling of 1,3‐Dienes and Carboxylic Acid Anhydrides

AbstractCatalytic chemo‐, regio‐ and enantioselective construction of allyl‐Cu complexes generated from a Cu−H addition to trans‐1,3‐dienes followed by in situ addition to anhydrides to construct homoallylic alcohols is presented. This method is distinguished by a characteristic pathway to generate enantiomerically enriched allyl‐Cu species, which react with a wide range of anhydrides in high chemo‐, regio‐ and stereoselectivity. Functionalization of homoallylic alcohol products provides useful building blocks which are otherwise difficult to obtain.

Early Organic Chemistry in Kyiv: Serhii Mykolayovych Reformatskyi (1860-1934) and his Name Reaction.

Serhiy Mykolayovych Reformatskyi, [Ukrainian: Рeφopмaтcьκий, Cepгiй Mиκoлaйoвич; Russian: Sergei Nikolaevich Reformatskii, РeΦopмaтcκий, Cepгeй Hиκoлaeвич (1860-1934)] was a product of Zaitsev's laboratory in Kazan Imperial University in Russia and one of the founding fathers of organic chemistry in Ukraine. He discovered his eponymous reaction while a graduate student in Kazan under Zaitsev, studying the synthesis of homoallylic alcohols. He modified this reaction by replacing the olefinic π bond of an allyl halide with a carbonyl group. In the prototype reaction, he treated ethyl haloacetates with zinc and aldehydes or ketones. The reaction gave the corresponding β-hydroxyesters and remains an important synthetic method. Work on the reaction over the ensuing century and a quarter has led to the discovery of analogous reactions using a wide range of metals, and even permitting the use of water as a solvent.

Diastereodivergent and Enantioselective Synthesis of Homoallylic Alcohols via Nickel-Catalyzed Borylative Coupling of 1,3-Dienes with Aldehydes.

We present the first enantioselective nickel-catalyzed borylative coupling of 1,3-dienes with aldehydes, providing an efficient route to highly valuable homoallylic alcohols in a single step. The reaction involves the 1,4-carboboration of dienes, leading to the formation of C-C and C-B bonds accompanied by the construction of two continuous stereogenic centers. Enabled by a chiral spiro phosphine-oxazoline nickel complex, this transformation yields products with exceptional diastereoselectivity, E-selectivity, and enantioselectivity. The diastereoselectivity of the reaction can be controlled by employing either (Z)-1,3-dienes or (E)-1,3-dienes.

Role of curvature in acridone for 1 O2 oxidation of a natural product homoallylic alcohol: A novel iso-hydroperoxide intermediate.

A density functional theoretical (DFT) study is presented, implicating a 1 O2 oxidation process to reach a dihydrobenzofuran from the reaction of the natural homoallylic alcohol, glycocitrine. Our results predict an interconversion between glycocitrine and an iso-hydroperoxide intermediate [R(H)O+ -O- ] that provides a key path in the chemistry which then follows. Formations of allylic hydroperoxides are unlikely from a 1 O2 'ene' reaction. Instead, the dihydrobenzofuran arises by 1 O2 oxidation facilitated by a 16° curvature of the glycocitrine ring imposed by a pyramidal N-methyl group. This curvature facilitates the formation of the iso-hydroperoxide, which is analogous to the iso species CH2 I+ -I- and CHI2 + -I- formed by UV photolysis of CH2 I2 and CHI3 . The iso-hydroperoxide is also structurally reminiscent of carbonyl oxides (R2 C=O+ -O- ) formed in the reaction of carbenes and oxygen. Our DFT results point to intermolecular process, in which the iso-hydroperoxide's fate relates to O-transfer and H2 O dehydration reactions for new insight into the biosynthesis of dihydrobenzofuran natural products.

Turning Homoallylic Alcohols into Aliphatic Ketones under Nickel Catalysis

Turning Homoallylic Alcohols into Aliphatic Ketones under Nickel Catalysis

Nickel-Catalyzed Isomerization of Homoallylic Alcohols

Nickel-catalyzed isomerizations of homoallylic alcohols and a bishomoallylic alcohol are presented. These isomerization reactions occur in the presence of a simple nickel catalyst that does not require addition of an exogenous ligand. The corresponding ketone products are generated in ≤98% yield.

Photocatalytic Metal Hydride Hydrogen Atom Transfer Mediated Allene Functionalization by Cobalt and Titanium Dual Catalysis

AbstractCatalytic metal hydride hydrogen atom transfer (MHAT) reactions have proven to be a powerful method for alkene functionalization. This work reports the discovery of Co‐porphines as highly efficient MHAT catalysts with a loading of only 0.01 mol % for unprecedented chemoselective allene functionalization under photoirradiation. Moreover, the newly developed bimetallic strategy by the combination of photo Co‐MHAT and Ti catalysis enabled the successful carbonyl allylation with a wide range of amino, oxy, thio, aryl, and alkyl‐allenes providing expedient access to valuable β‐functionalized homoallylic alcohols in over 100 examples with exceptional regio‐ and diastereoselectivity. Mechanism studies and DFT calculations supported that selectively transferring hydrogen atoms from cobalt hydride to allenes and generating allyl radicals is the key step in the catalytic cycle.

Photocatalytic Metal Hydride Hydrogen Atom Transfer Mediated Allene Functionalization by Cobalt and Titanium Dual Catalysis.

Catalytic metal hydride hydrogen atom transfer (MHAT) reactions have proven to be a powerful method for alkene functionalization. This work reports the discovery of Co-porphines as highly efficient MHAT catalysts with a loading of only 0.01 mol % for unprecedented chemoselective allene functionalization under photoirradiation. Moreover, the newly developed bimetallic strategy by the combination of photo Co-MHAT and Ti catalysis enabled the successful carbonyl allylation with a wide range of amino, oxy, thio, aryl, and alkyl-allenes providing expedient access to valuable β-functionalized homoallylic alcohols in over 100 examples with exceptional regio- and diastereoselectivity. Mechanism studies and DFT calculations supported that selectively transferring hydrogen atoms from cobalt hydride to allenes and generating allyl radicals is the key step in the catalytic cycle.