Organophosphates as Versatile Substrates in Organic Synthesis.

This review summarizes the applications of organophosphates in organic synthesis. After a brief introduction, it discusses cross-coupling reactions, including both transition-metal-catalyzed and transition-metal-free substitution reactions. Subsequently, oxidation and reduction reactions are described. In addition, this review highlights the applications of organophosphates in the synthesis of natural compounds, demonstrating their versatility and importance in modern synthetic chemistry.

Tuning the Photophysical Properties of Flavins by Attaching an Aryl Moiety via Direct C-C Bond Coupling.

Palladium-catalyzed Suzuki reactions of brominated flavin derivatives (5-deazaflavins, alloxazines, and isoalloxazines) with boronic acids or boronic acid esters that occur readily under mild conditions were shown to be an effective tool for the synthesis of a broad range of 7/8-arylflavins. In general, the introduction of an aryl/heteroaryl group by means of a direct C-C bond has been shown to be a promising approach to tuning the photophysical properties of flavin derivatives. The aryl substituents caused a bathochromic shift in the absorption spectra of up to 52 nm and prolonged the fluorescence lifetime by up to 1 order of magnitude. Moreover, arylation of flavin derivatives decreased their ability to generate singlet oxygen.

Substrate-Controlled Regioselective Bromination of 1,2-Disubstituted Cyclobutenes: An Application in the Synthesis of 2,3-Disubstituted Cyclobutenones.

Easily available disubstituted cyclobutenes were regioselectively halogenated at the allylic position by means of a reaction with bromine. The regioselectivity of bromination is controlled by the presence of a carbocation-stabilizing group. The prepared disubstituted 3-bromocyclobutenes were converted into the corresponding disubstituted cyclobutenones. On the basis of the performed experiments, the mechanism behind the bromination reaction was also proposed.

Recent Progress Concerning the N-Arylation of Indoles.

This review summarizes the current state-of-the-art procedures in terms of the preparation of N-arylindoles. After a short introduction, the transition-metal-free procedures available for the N-arylation of indoles are briefly discussed. Then, the nickel-catalyzed and palladium-catalyzed N-arylation of indoles are both discussed. In the next section, copper-catalyzed procedures for the N-arylation of indoles are described. The final section focuses on recent findings in the field of biologically active N-arylindoles.

Room-Temperature Negishi Reaction of Trisubstituted Vinyl Phosphates for the Synthesis of Tetrasubstituted Alkenes.

The present study investigated the ability of bromovinyl phosphates to react with organozinc reagents at room temperature during palladium-catalyzed reactions. It was determined that both the bromine atom and the phosphate group were successfully substituted by means of the reaction with the organozinc reagents, thereby allowing for the synthesis of cyclic and acyclic tetrasubstituted double bonds. The low stability of the organozinc compounds in an acidic environment was exploited to accomplish the synthesis of alkenes using a one-pot, two-step experimental setup.

Indolylboronic Acids: Preparation and Applications.

Indole derivatives are associated with a variety of both biological activities and applications in the field of material chemistry. A number of different strategies for synthesizing substituted indoles by means of the reactions of indolylboronic acids with electrophilic compounds are considered the methods of choice for modifying indoles because indolylboronic acids are easily available, stable, non-toxic and new reactions using indolylboronic acids have been described in the literature. Thus, the aim of this review is to summarize the methods available for the preparation of indolylboronic acids as well as their chemical transformations. The review covers the period 2010-2019.

The synthesis of polysubstituted indoles from 3-bromo-2-indolyl phosphates.

A novel methodology for the synthesis of functionalised indoles based on the cross-coupling reactions of 3-bromo-2-indolyl phosphates is described. The preparation involves the conversion of easily available 2-oxindoles to 3,3-dibromo-2-oxindoles followed by the Perkow reaction affording 3-bromo-2-indolyl phosphates. Then bromine atom is substituted regioselectively by the Suzuki coupling reaction. We observed that aluminum chloride promoted the reaction of 3-substituted-2-indolyl phosphates with organozinc reagents furnishing 2,3-disubstituted indoles as final products. The overall diversity and efficiency of the methodology was demonstrated by the synthesis of bioactive molecule from easily available substances.

Fast singlet excited-state deactivation pathway of flavin with a trimethoxyphenyl derivative.

Incorporation of the trimethoxyphenyl group at position 7 of flavin can drastically change the photophysical properties of flavin. We show unique fast singlet 1(π,π*) excited state deactivation pathway through nonadiabatic transition to the 1(n,π*) excited- state, and subsequent deactivation to the ground electronic state (S0), closing the photocycle. This mechanism explains the exceptionally weak fluorescence and the short excited-state lifetime for the flavin trimethoxyphenyl derivative and the lack of excited triplet T1 state formation. Full recovery of flavin in its ground state takes place within a 15 ps time window after photoexcitation in a polar solvent such as acetonitrile. According to quantum chemical calculations, the C(2)-O distance elongates by 0.16 Å in the 1(n,π*) state, with respect to the ground state. Intermediate-state structures are predicted by theoretical ab initio calculations and their dynamics are investigated using broadband vis-NIR time-resolved transient absorption and fluorescence up-conversion techniques.

Arylethyne Bromoboration-Negishi Coupling Route to E- or Z-Aryl-Substituted Trisubstituted Alkenes of ≥98% IsomericPurity. New Horizon in the Highly Selective Synthesis of Trisubstituted Alkenes.

The hitherto unprecedented palladium-catalyzed cross-coupling of (Z)-ß-bromo-ß-arylethenylboranes can be made to proceed satisfactorily through (1) the use of highly catalytically active bis(tri-tert-butylphosphine)palladium or dichloro[N,N-bis-(2,6-diisopropylphenyl)imidazol-2-yl](m-chloropyridine)palladium and (2) conversion of dibromoboryl group to (pinacol)boryl group. Thus, a wide variety of carbon groups can be used to substitute bromine in ≥98% stereo- and regioselectivity, while suppressing the otherwise dominant ß-debromoboration. Together with the alkylethyne-based protocols, the alkyne bromoboration-Negishi coupling tandem process has emerged as the most widely applicable and highly selective route to trisubstituted alkenes including those that are otherwise difficult to access.

Highly(≥98%) Selective Trisubstituted Alkene Synthesis of Wide Applicability via Fluoride-Promoted Pd-Catalyzed Cross-Coupling of Alkenylboranes.

(Z)-ß-bromo-1-propenyl(pinacol)borane(4), recently made available in 85% yield as a ≥98% isomerically pure compound via bromoboration of 1-propyne, has been converted to ß-alkyl-, aryl-, and alkenyl-substituted (Z)-2-methyl-1-alkenyl(pinacol)boranes(2a) in ca. 75% yield based on propyne via Pd-catalyzed Negishi alkenylation with suitable organozinc bromide. The previously sluggish and modest-yielding Suzuki alkenylation of ß,ß-disubstituted alkenylboranes has been significantly promoted by fluorides, especially nBu4NF(TBAF) or CsF to give trisubstituted alkenes, i.e., (Z)-ß-Me-substituted 3-i-3-xi and (E)-ß-Ph-substituted 2b-i and 2b-ii. In all cases, each alkene product was formed in a ≥98% seteoselectivity. The propyne-based protocol nicely complements the widely used Zr-catalyzed alkyne methylalumination-Pd-catalyzed alkenylation by providing a highly stereoselective(≥98%) route to (Z)-Me-substituted alkenes.

Formation of trisubstituted buta-1,3-dienes and α,ß-unsaturated ketones via the reaction of functionalized vinyl phosphates and vinyl phosphordiamidates with organometallic reagents.

We studied the reactions of vinyl phosphates and vinyl phosphordiamidates containing an ester functional group with organometallic reagents. We found that the functionalized vinyl phosphates were smoothly converted into tri- and tetrasubstituted buta-1,3-dienes via the reaction with aryllithium reagents. Moreover, the vinyl phosphordiamidates were converted into α,ß-unsaturated ketones using Grignard reagents. Based on the performed experiments, we proposed a reaction mechanism, which was confirmed by means of the isolation of key intermediates.

Formal Transition-Metal-Catalyzed Phosphole C-H Activation for the Synthesis of Pentasubstituted Phospholes.

Unprecedented formal transition-metal-catalyzed phosphole C-H functionalization is described in this paper. Pentasubstituted phospholes were prepared via the copper-catalyzed reaction of 1,3,4-trisubstituted phosphole with aryl iodides or bromides under distinct conditions. The developed methodology is able to accommodate a wide variety of substituents, including aryl, heteroaryl, and alkenyl.

Dearomatization Strategy for the Synthesis of Arylated 2H-Pyrroles and 2,3,5-Trisubstituted 1H-Pyrroles.

The first high-yielding route to arylated 2H-pyrroles was developed. The methodology utilizes 2,5-disubstituted pyrroles that are metalated, and the aryl substituents are introduced by a palladium-catalyzed cross-coupling reaction. The prepared pyrroles can be rearranged to 2,3,5-trisubstituted pyrroles under acidic conditions. Attempts to convert the 2,3,5-trisubstituted pyrroles to 2,3,4,5-tetrasubstituted pyrroles by the dearomatization rearrangement strategy were unsuccessful.

Selective magnesiation of chloro-iodopurines: an efficient approach to new purine derivatives.

[reaction: see text] Both 6-chloro-2-iodo-9-isopropylpurine (1) and 2-chloro-6-iodo-9-benzylpurine (4) undergo a selective I/Mg exchange reaction with iPrMgCl at -80 degrees C. The reaction course at 0 degrees C is different. Magnesiation of 1 proceeds with the migration of magnesium to the 8 position of the purine nuclei. In the case of 4, substitution of iodine with an alkyl group from the Grignard reagent accompanied with a Cl/Mg exchange reaction takes place, and 6-alkyl-2-magnesiated purines (9) are formed. Thus prepared Grignard reagents afford the corresponding alcohols by the reaction with aldehydes.

Modular and highly stereoselective approach to all-carbon tetrasubstituted alkenes.

A modular and completely stereoselective approach for the construction of all-carbon tetrasubstituted alkenes is described. It is based on the three-fold, sequential metal-catalyzed, cross-coupling functionalization of simple enolphosphate dibromide templates with carbon nucleophiles, affording tetrasubstituted alkenes as single isomers.

6-Magnesiated purines: preparation and reaction with aldehydes.

[reaction: see text] Halogen-metal exchange reaction of 9-benzyl-6-iodopurine with iPrMgCl in toluene at -80 degrees C proceeds almost quantitatively. Such a purine-derived Grignard reagent reacts selectively with aldehydes in toluene, giving the corresponding alcohols in 25-62% yield, while other functional groups such as ketones, esters, and nitriles do not react under these conditions. The reaction can be extended to protected 6-iodopurine ribonucleoside.

Use of residual dipolar couplings in conformational analysis of meta-disubstituted calix[4]arenes.

Dimercuration of tetrapropoxy calix[4]arene followed by a reaction with isoamyl nitrite afforded dinitroso regioisomers with unique substitution patterns. The unusual conformational behaviour of these inherently chiral systems was revealed by the combination of dynamic NMR and residual dipolar coupling (RDC) techniques.

Selective synthesis of 7-substituted purines via 7,8-dihydropurines.

A simple and efficient protocol for the preparation of 7-substituted purines is described. 6- and 2,6-Dihalopurines were N(9)-tritylated and then transformed to 7,8-dihydropurines by DIBAL-H. Subsequent N(7)-alkylation followed by N(9)-trityl deprotection with trifluoroacetic acid was accompanied by spontaneous reoxidation, which led to the 7-substituted purines at 55-88% overall isolated yields.

Highly regio- and stereoselective synthesis of (Z)-trisubstituted alkenes via propyne bromoboration and tandem Pd-catalyzed cross-coupling.

Contrary to all previous reports, bromoboration of propyne with BBr(3) proceeds in >or=98% syn-selectivity to produce (Z)-2-bromo-1-propenyldibromoborane (1). Although 1 is readily prone to stereoisomerization, it can be converted to the pinacolboronate (2) of >or=98% isomeric purity by treatment with pinacol, which may then be subjected to Negishi coupling to give trisubstituted (Z)-alkenylpinacolboronates (3) containing various R groups in 73-90% yields. Iodinolysis of 3 affords alkenyl iodides (4) in 80-90% yields. All alkenes isolated and identified are >or=98% Z.