Synthesis of N-heterocyclic diols by diastereoselective pinacol coupling reactions

A series of 5-8 membered N-heterocyclic diols have been prepared from acyclic dicarbonyls via diastereoselective pinacol reactions whereby cis- or trans-diol stereoselectivity is controlled by the choice of low-valent metal reagent used.     

Samarium(ii) iodide-mediated intramolecular pinacol coupling reactions with cyclopropyl ketones

The first reported intramolecular pinacol coupling of cyclopropyl ketones has been achieved, demonstrating that cyclisation competes favourably with ring-opening of the cyclopropyl ketyl radical.     

Samarium diiodide-induced intramolecular pinacol coupling of dinitrones: synthesis of cyclic cis-vicinal diamines

Pinacol coupling of alkyl dinitrones mediated by SmI2 was achieved in the presence of a proton source allowing the synthesis of cyclic vicinal diamines with good cis-selectivity.     

Influence of chelating silyl scavengers on the diastereoselectivity of chromium catalyzed pinacol cross couplings

The choice of the silyl scavenger shows a substantial influence on the diastereoselectivity of the chromium catalyzed pinacol cross coupling. In the case of the intramolecular cyclization, two competing effects are observed. If the silylation reagents contain chelating heteroatoms in the side chain, a remarkable trans-selectivity is observed. Conversely the cis-diols are preferred if bulky substituted scavengers are used. A suitable transition state model for this reaction is reported, based on formerly published results.     

Chromium(II)-catalyzed diastereoselective pinacol type cross coupling: studies of substrate-controlled effects

Using 20 mol % of CrCl₂ as catalyst, manganese powder as reducing agent, and TMS-Cl as scavenger, various acroleins and aldehydes were coupled with moderate to high yields and diastereomeric excesses. Alkyl aldehydes usually favor syn configuration while aldehydes with functional groups containing chelating hetero atoms promote the formation of anti configuration. Using sterically demanding alkyl residues on the acrolein substrate, the syn configuration is definitely preferred.     

Samarium diiodide-mediated reductive couplings of chiral nitrones with aldehydes/ketones and acyl chlorides

The SmI₂-mediated and H₂O-promoted reductive cross-coupling reactions of the l-tartaric acid derived nitrone (3S,4S)-8 with aldehydes/ketones, and the l-malic acid derived nitrone (S)-6 with aliphatic acyl chlorides have been investigated, respectively. (2R,3S,4S)-1,3,4-Trihydroxyprolinol derivatives 9a-f were obtained with high C-2/C-3 trans-selectivities, and 72:28-85:15 diastereoselectivities at the carbinol center from aromatic ketones/aldehydes, while low diastereoselectivities for aliphatic aldehydes. Conditions have been established for the syntheses of (2R,3S,4S)-3,4-dihydroxyprolinol derivatives such as 18, by N-O bond cleavage of the corresponding N-hydroxyprolinol derivatives 9b-f, or more conveniently by a one-pot reductive coupling of nitrone 8 and in situ N-O bond cleavage of the resultant coupling product. The 2-acyl-3-benzyloxy-1-hydroxypyrrolidines 10a-f were formed in 48-82% yields, and in 74:26-78:22 diastereoselectivities. It was revealed that the amount of water required for the reaction is substrate-depending.     

Samarium mediated pinacol coupling of carbonyl compounds in the presence of a catalytic amount of iodine under aqueous media

In the presence of a catalytic amount of iodine, metallic samarium mediated pinacol coupling of carbonyl compounds has been carried out under saturated aqueous NH4Cl-THF conditions at room temperature. It gives corresponding 1,2-diols in good yields.     

Samarium diiodide-induced couplings of carbonyl compounds with methoxyallene leading to 4-hydroxy 1-enol ethers

A surprising samarium diiodide-induced coupling reaction of carbonyl compounds with methoxyallene provided 4-hydroxy 1-enol ethers, which are versatile synthetic building blocks. In this coupling reaction, methoxyallene serves as an acrolein equivalent, which cannot directly be employed. [reaction: see text]     

A highly diastereoselective pinacol coupling reaction of aldehydes and ketones using low-valence niobium generated from Nb(V)

A simple method for the diastereoselective synthesis of racemic 1,2-diol mediated by low-valence niobium generated in situ is described. A 1,4-dioxane-toluene solvent system was found to be essential to achieve higher selectivities and to prevent other reactions of pinacols, such as deoxygenation and acetal formation. Aromatic aldehydes and ketones were converted to the corresponding pinacols with up to 97 and 85% de, respectively.     

Catalytic, highly enantio- and diastereoselective pinacol coupling reaction with a new tethered bis(8-quinolinolato) ligand

A new class of chiral ligand, tethered bis(8-quinolinol) (TBOxH), is developed. Its chromium complex, TBOxCrCl (3 mol %), effectively catalyzes the pinacol coupling reaction of aromatic aldehydes at room temperature with high yield (up to 94%), high diastereoselectivity (up to dl:meso = 98:2), and high enantioselectivity (up to 98%). The scope of the present method turns out not to be limited to aromatic aldehyde derivatives, as cyclohexanecarboxaldehyde undergoes pinacolization as well (44% yield, dl:meso = 93:7, 84% ee). The method provides an efficient access to enantioenriched 1,2-diols.     

Conjugated polymers as photoredox catalysts: a new catalytic system using visible light to promote aryl aldehyde pinacol couplings

The conjugated polymer poly-(p)-phenylene (PPP) was synthesized and used as a photoredox catalyst to promote pinacol coupling of aryl-aldehydes with visible light. The reaction required the use of a sacrificial electron donor (Et₃N), and was accelerated by the addition of Lewis and Brønsted acids. A distinct advantage of this photocatalytic system is the robust nature of the system, which is not overly sensitive to impurities, oxygen, or temperature, and proceeds cleanly with few side reactions. As a comparison with the PPP system, the reactivity of Ru(bpy)₃Cl₂, a popular photoredox catalyst was compared. The PPP system was superior to the Ru(bpy)₃Cl₂ for the pinacol couplings in both rate and yield.     

Mg-promoted mixed pinacol coupling

Mg-promoted reduction of a mixture of aromatic ketones (or imines) and aliphatic carbonyl compounds in N,N-dimethylformamide (DMF) brought about unique mixed pinacol type of cross coupling to give unsymmetrical vicinal diols (or amino alcohols) or α-hydroxyketones in good to moderate yields. The reaction may be initiated by electron transfer from magnesium metal to an aromatic carbonyl compound possessing a less negative reduction potential. The difference of reduction potential between aromatic ketones (or imines) and aliphatic carbonyl compounds was found to be one of the important key factors in this selective cross coupling.     

Samarium(II)-mediated pinacol coupling in water: occurrence of unexpected disproportionation and action of low-valent samarium as an active species

[reaction: see text] Mechanistic studies of one-electron reduction in water using samarium were carried out. Unexpected disproportionation in water was observed via UV-vis spectroscopic analysis. This fact indicates that low-valent samarium species can exist in water. Furthermore, the SmCl(3)-Sm and SmCl(3)-Mg systems were found to act as good one-electron reducing agents in water.     

Photochemical pinacol rearrangements of unsymmetrical diols

The photochemical pinacol reaction of a series of nonsymmetrical 9-fluorenyl-substituted vic-diols was investigated and compared with their acid-catalyzed thermal reaction. Unlike the thermal reaction, the radiation-induced processes involve only fluorenyl cations, as is reflected in differences of product distribution between the two reactions. From the product studies, substituent migratory aptitudes are reversed in the photochemical process, suggesting that kinetic control takes place under neutral conditions unlike the acid-catalyzed thermal reactions. The presence of fluorenyl cation intermediates and their lifetimes were established by laser flash spectroscopy studies.     

Vanadium-catalyzed pinacol coupling reaction in water

A catalytic pinacol coupling using water as a solvent was performed by a catalytic amount of vanadium(III) chloride and metallic Al as a co-reductant. A combination forms a binary catalytic system, being in sharp contrast to the reaction in organic solvent, which requires a chlorosilane as an additive. Various aromatic aldehydes underwent the reductive coupling to give the corresponding 1,2-diols in moderate to good yields.     

Sulfinyl-directed diastereoselective

Introduction of a homochiral p-tolylsulfinyl group at an appropriate position in the alkene accelerates the thermal [5C + 2C] intramolecular cycloaddition to beta-silyloxy-gamma-pyrones and, most importantly, leads to excellent levels of diastereodifferentiation. The resulting adducts can be easily desulfinylated to give optically active 8-oxabicyclic[3.2.1]octane intermediates which by virtue of their rich functionalization might be susceptible to elaboration into enantiomerically pure natural products containing seven-membered carbocycles and tetrahydrofurans.     

Further studies on the pinacol coupling reaction

The pinacol coupling of R(+)3-methylcyclohexanone gives a product distribution $\text{dependent on the mode of coupling}$. Similar changes in product composition are also seen in the coupling of 4-methylcyclohexanone and in the mixed coupling of 3-methylcyclohexanone with cyclohexanone. In $\text{all cases studied}$, the [Al-Hg] method results in products having an axial methyl group. An X-ray structure of a product containing two axial methyl groups is presented.     

Migratory aptitudes in pinacol rearrangement of vic-dihydroxychlorins

When vic-dihydroxychlorins undergo a pinacol-pinacolone rearrangement, the migratory aptitudes of common porphyrin substituents follow the order: alkyl groups, propionate side chain, H > methyl group > acetate side chain. C-Alkylchlorins can be made by extremely short syntheses utilizing such rearrangement.