Homoallylic Alcohols Research Articles

Synthesis of α-Boryl-α-Substituted Allylboronates from Propyne.

A novel method for the two-step synthesis of α-boryl-α-substituted allylboronates from propyne is described. These allylboronates are prepared by the Co-catalyzed 1,1-diboration reaction of propyne with B2pin2, followed by the base-mediated alkylation reaction of 1,1-di(boryl)propene at the α-position. Computational studies revealed the origins of observed reactivity and selectivity in the base-mediated alkylation reaction. The resulting α-boryl-α-methyl-allylboronate is applied to the allylation of aldehydes, which gives homoallylic alcohols with a trisubstituted alkene moiety.

Radical‐Based Enantioconvergent Reductive Couplings of Racemic Allenes and Aldehydes

AbstractTransition metal‐catalyzed radical‐based enantioconvergent reactions have become a powerful strategy to synthesize enantiopure compounds from racemic starting materials. However, existing methods primarily address precursors with central chirality, neglecting those with axial chirality. Herein, we describe the enantioconvergent reductive coupling of racemic allenes with aldehydes, facilitated by a photoredox, chromium, and cobalt triple catalysis system. This method selectively affords one product from sixteen possible regio‐ and stereoisomers. The protocol leverages CoIII−H mediated hydrogen atom transfer (MHAT) and Cr‐catalyzed radical‐polar crossover for efficient stereoablation of axial chirality and asymmetric addition, respectively. Supported by mechanistic insights from control experiments, deuterium labeling, and DFT calculations, our approach offers synthetic chemists a valuable tool for creating enantioenriched chiral homoallylic alcohols, promising to advance radical‐based strategies for synthesizing complex chiral molecules.

Radical-Based Enantioconvergent Reductive Couplings of Racemic Allenes and Aldehydes.

Transition metal-catalyzed radical-based enantioconvergent reactions have become a powerful strategy to synthesize enantiopure compounds from racemic starting materials. However, existing methods primarily address precursors with central chirality, neglecting those with axial chirality. Herein, we describe the enantioconvergent reductive coupling of racemic allenes with aldehydes, facilitated by a photoredox, chromium, and cobalt triple catalysis system. This method selectively affords one product from sixteen possible regio- and stereoisomers. The protocol leverages CoIII-H mediated hydrogen atom transfer (MHAT) and Cr-catalyzed radical-polar crossover for efficient stereoablation of axial chirality and asymmetric addition, respectively. Supported by mechanistic insights from control experiments, deuterium labeling, and DFT calculations, our approach offers synthetic chemists a valuable tool for creating enantioenriched chiral homoallylic alcohols, promising to advance radical-based strategies for synthesizing complex chiral molecules.

Cobalt-Catalyzed Carbonylative Cyclization of Homoallylic Alcohols and Amines

Cobalt-Catalyzed Carbonylative Cyclization of Homoallylic Alcohols and Amines

Catalyst-Free Dearomative Allylboration of Ketones with Benzo[b]thiophenylmethyl Boronic Acids.

A novel approach to the dearomative allylboration of ketones with benzo[b]thiophenylmethyl boronic acids has been developed. By leveraging the inherent reactivity of the boronic acid unit, this process occurs under mild reaction conditions without the need for a catalyst, leading to the efficient formation of homoallylic tertiary alcohols accompanied by the construction of three-dimensional sulfur-containing alicyclic scaffolds in high yields with excellent stereoselectivities.

Stereodivergent syntheses of diospongins A and B

Syntheses of the tetrahydropyranol natural products (±)-diospongin A and (±)-diospongin B, in four steps (37 % overall) and seven (14 % overall) or nine steps (25 % overall) respectively, are reported. A common homoallylic alcohol serves as a key intermediate for stereodivergent, one-pot olefin metathesis/deprotection/oxa-Michael cyclization steps that establish the requisite 2,6-stereochemical relationships of the diastereomeric targets. Cross metathesis results in formation of an acyclic, unsaturated ketone that undergoes conjugate addition to give diospongin A directly. Ring-closing metathesis/conjugate addition provides a diastereomerically pure bicyclic lactone, possessing the contra-thermodynamic 2,6-trans stereochemistry, that can be converted to diospongin B in either two or four steps.

Three‐Component Allylic Alkylation Reaction of α‐Diazo Ketones with Water and Allyl Carbonates for Construction of Homoallylic Alcohols

AbstractA three‐component allylic alkylation reaction of α‐diazo ketones, water and allyl carbonate under the cooperative catalysis of Rh2(OAc)4, Pd2(dba)3 and Brønsted acid was disclosed. This method provides an expeditious access to α‐keto homoallylic alcohols in good to high yields. Controlled experiments support that the transformations proceed through cross‐interception of two active intermediates Pd‐allyl species and enol intermediates derived from oxonium ylides. Moreover, synthetic transformations of the generated products enable the creation of motifs enriched with dense functional groups, underscoring their potential as valuable building blocks.

Redox-Neutral 1,2-Dicarbofunctionalization of Buta-1,3-diene by Merging Decatungstate and Chromium Catalysis

AbstractHomoallylic alcohol is a significantly useful intermediate in organic synthesis. Here we establish a three-component Nozaki–Hiyama–Kishi (NHK) type reaction of buta-1,3-diene, aldehydes, and aliphatic C–H partners by merging decatungstate and chromium catalysis, enabling a modular, redox-neutral, and atom-economic strategy to access a diverse range of homoallylic alcohols.

Palladium mediated domino heck redox cyclization of aromatic homoallylic alcohols to methylindanones

Palladium mediated domino heck redox cyclization of aromatic homoallylic alcohols to methylindanones

Radical Allylation of Aldehydes with Allenes by Photoredox Cobalt and Chromium Dual Catalysis

AbstractA dual cobalt and chromium photoredox-catalyzed allylation of aldehydes with allenes through a photo metal-hydride atom transfer (MHAT) process has been developed to yield homoallylic alcohols with exceptional diastereoselective control. This sustainable and efficient method holds significant promise for applications in the synthesis of valuable organic compounds.

Organic Dye Photocatalyzed Synthesis of Functionalized Lactones and Lactams via a Cyclization-Alkynylation Cascade.

An organic dye photocatalyzed lactonization-alkynylation of easily accessible homoallylic cesium oxalates using ethynylbenziodoxolone (EBX) reagents has been developed. The reaction gave access to valuable functionalized lactones and lactams in up to 88% yield via the formation of two new C-C bonds. The transformation was carried out on primary, secondary, and tertiary homoallylic alcohols and primary homoallylic amines and could be applied to the synthesis of spirocyclic compounds as well as fused and bridged bicyclic lactones.

Hydrogen Source Tuned Regiodivergent Asymmetric Hydroalkylations of 2‐Substituted 1,3‐Dienes with Aldehydes by Cobalt‐Catalysis

AbstractCatalytic methods allowing for the reliable prediction and control of diverse regioselectivity along with the control of enantioselectivity to access different regio‐ and enantiomers by switching the least reaction parameters are one of the most attractive ways in organic synthesis, which provide access to diverse enantioenriched architectures from identical starting materials. Herein, a Co‐catalyzed regiodivergent and enantioselective reductive hydroalkylation of 1,3‐dienes with aldehydes has been achieved, furnishing different enantioenriched homoallylic alcohol architectures in good levels of enantioselectivity. The reaction features the switch of regioselectivity tuned by the selection of proton source. The use of an acid as proton source provided asymmetric 1,2‐hydroalkylation products under reductive conditions, yet asymmetric 4,3‐hydroalkylation products were obtained with silane as hydride source. This catalytic protocol allows for the access of homoallylic alcohols with two continuous saturated carbon centers in good levels of regio‐, diastereo‐, and enantioselectivity.

Hydrogen Source Tuned Regiodivergent Asymmetric Hydroalkylations of 2-Substituted 1,3-Dienes with Aldehydes by Cobalt-Catalysis.

Catalytic methods allowing for the reliable prediction and control of diverse regioselectivity along with the control of enantioselectivity to access different regio- and enantiomers by switching the least reaction parameters are one of the most attractive ways in organic synthesis, which provide access to diverse enantioenriched architectures from identical starting materials. Herein, a Co-catalyzed regiodivergent and enantioselective reductive hydroalkylation of 1,3-dienes with aldehydes has been achieved, furnishing different enantioenriched homoallylic alcohol architectures in good levels of enantioselectivity. The reaction features the switch of regioselectivity tuned by the selection of proton source. The use of an acid as proton source provided asymmetric 1,2-hydroalkylation products under reductive conditions, yet asymmetric 4,3-hydroalkylation products were obtained with silane as hydride source. This catalytic protocol allows for the access of homoallylic alcohols with two continuous saturated carbon centers in good levels of regio-, diastereo-, and enantioselectivity.

Nickel-Catalyzed Asymmetric Borylative Coupling of 1,3-Dienes with Aldehydes

AbstractThe nickel-catalyzed borylative coupling of aldehydes and 1,3-dienes with diboron reagents offers an efficient method for synthesizing valuable homoallylic alcohols from easily accessible starting materials. However, achieving enantioselectivity in this reaction has been a significant challenge. We discuss our recent report on the first example of a nickel-catalyzed enantioselective borylative coupling of aldehydes with 1,3-dienes, employing a chiral spiro-phosphine–oxazoline ligand. Notably, by utilizing (E)-1,3-dienes or (Z)-1,3-dienes, we can reverse the diastereoselectivity, yielding either anti- or syn-products, respectively.

Photoinduced Platinum-Catalyzed Reductive Allylation of α-Diketones with Allylic Carbonates.

A unique process for the photoinduced platinum-catalyzed reductive allylation of α-diketones with allylic carbonates has been developed. This allylation reaction was found to proceed selectively at the more electron-deficient carbonyl group of the diketone to afford an α-keto homoallylic alcohol. Such products could be further derivatized by transformation of the remaining carbonyl group. A mechanistic investigation suggests that a ketyl radical generated in response to photoirradiation reacts with a (π-allyl)platinum complex to form a C-C bond.

A catalytic process enables efficient and programmable access to precisely altered indole alkaloid scaffolds.

A compound's overall contour impacts its ability to elicit biological response, rendering access to distinctly shaped molecules desirable. A natural product's framework can be modified, but only if it is abundant and contains suitably modifiable functional groups. Here we introduce a programmable strategy for concise synthesis of precisely altered scaffolds of scarce bridged polycyclic alkaloids. Central to our approach is a scalable catalytic multi-component process that delivers diastereo- and enantiomerically enriched tertiary homoallylic alcohols bearing differentiable alkenyl moieties. We used one product to launch progressively divergent syntheses of a naturally occurring alkaloid and its precisely expanded, contracted and/or distorted framework analogues (average number of steps/scaffold of seven). In vitro testing showed that a skeleton expanded by one methylene in two regions is cytotoxic against four types of cancer cell line. Mechanistic and computational studies offer an account for several unanticipated selectivity trends.

1,3-Butadiene Dicarbofunctionalization Enabled by the Dual Role of Diaryl Ketone in Photo-HAT/Chromium Catalysis.

We report a three-component Nozaki-Hiyama-Kishi type reaction of 1,3-dioxolane, 1,3-butadienes, and aldehydes to access masked aldehyde-incorporated homoallylic alcohols, facilitated by photo-hydrogen atom transfer (HAT)/chromium dual catalysis. The diaryl ketone serves dual roles both in the HAT process and in facilitating the turnover of the chromium catalyst. A range of functional groups are tolerated owing to the mild conditions. Both aromatic and aliphatic aldehydes are suitable substrates for coupling with several 1,3-butadienes and 1,3-dioxolane.

Electrochemical Radical Retro-Allylation of Homoallylic Alcohols with Sulfonyl Hydrazides.

We report herein the first examples of electrochemical radical retro-allylation of homoallylic alcohols via the cleavage of the C(sp3)-C(sp3) bond. In this reaction, a variety of sulfonyl hydrazides were employed as the environmentally friendly radical sources via an electrochemical dehydrazination with the release of N2 and H2 as the byproducts, leading to sulfonyl allylic compounds in moderate to good yields. The reaction features metal- and base-free reaction conditions, broad functional group tolerance, and a broad substrate scope.

Regioselective Ring‐Opening of Oxetanes Catalyzed by Lewis Superacid Al(C6F5)3

AbstractThis study details an aluminum‐catalyzed regioselective isomerization of 2,2‐disubstituted oxetanes to yield homoallylic alcohols. The reaction takes place in toluene at 40 °C, employing 1 mol % of Al(C6F5)3 as catalyst. This catalytic system shows a wide substrate scope (12 examples). The optimized conditions are especially useful for electron‐rich aryl oxetanes, completely suppressing the formation of allyl isomers and reducing the amount of the dimer by‐product. The synthetic applicability of the reported methodology is demonstrated by the enantioselective formal synthesis of curcuquinone and the σ1 receptor agonist RC‐33.

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.