2020 Volume 3 Issue 5

INEOS OPEN, 2020, 3 (5), 156–164  Journal of Nesmeyanov Institute of Organoelement Compounds of the Russian Academy of Sciences Download PDF DOI: 10.32931/io2024r

Promising Routes of Application of Smart Allylborating Reagents

Abstract

Among the known allylborating agents, amine adducts of allylic triorganoboranes can be considered as the most advanced smart reagents since they combine high activity with stability and selectivity. The new reactivity profile of these compounds offers additional opportunities for both the laboratory and industrial application of allylboranes. The current review presents a short analysis of the promising routes of application of the amine adducts, which include, for example, the catalytic synthesis of functionalized allylarenes, homoallylamines, and the synthesis of BN isosteres of carbon aromatic systems.

Key words: allylboranes, amine adducts of allylboranes, allylboration, homoallylamines, 1,2-azaborines, Suzuki cross-coupling.

 

Highlight

Allylboranes and allylboration occupy an important place in the tools of synthetic organic chemistry [1–6]. The widespread use of allylic triorganoboranes in synthesis was initiated by the pioneer works of Yu. N. Bubnov and B. M. Mikhailov on allylboration of carbonyl compounds [7–9], which were successfully developed by H. C. Brawn [10], S. Masamune [11], J. A. Soderquist [12], and P. V. Ramachandran [13] into enantioselective allylboration of aldehydes, ketones, and imines. Owing to the boundary position of boron between metals and nonmetals in Mendeleev's Periodic Table, its allylic derivatives possess unique properties which distinguish them from the related compounds of lithium, magnesium, zinc, and others. The distinctive features of allylboranes (except for allylchloro- and allylbromoboranes [14]) are their high stability in the pure form which ensures their long-term storage and provides an opportunity for distillation (Scheme 1); the absence of basic properties which are characteristic of organometallic compounds; the covalent character of the C–B bond which energy is about 68 kcal/mol [15]; and the high Lewis acidity of the boron center.

Scheme 1. Properties of allylboranes.

The extremely high reactivity of allylic triorganoboranes directly correlates with the high Lewis acidity of the boron center, owing to which free boranes undergo instantaneous allylic rearrangement [16] and, in chemical transformations, efficiently activate the reaction center via coordination with the electron pairs of the Lewis bases (oxygen, sulfur, nitrogen, and carbon atoms), for example, С=О and С=N groups can be rapidly allylated even at –100 °С [13]. As a result, the allylboration always proceeds through the Zimmerman–Traxler six-membered cyclic transition state (TS) [17].

Among allylboranes, the triallyl derivatives are unsurpassed in terms of atom efficiency. A ballast part of the molecule is minimal and composes only 8% for triallylborane, which makes these boranes promising for industrial application. However, along with the exceptional reactivity and atom efficiency, allylic triorganoboranes have a range of serious drawbacks, such as high sensitivity to oxygen (the low-molecular allylboranes ignite spontaneously in the air), water, and alcohols, incompatibility with most of the functional groups. Furthermore, due to the high activity allylic triorganoboranes cannot be used in the catalytic allylboration of multiple С=О and С=N bonds [18].

These "unmodern" properties of triorganoboranes led to intensive development of the chemistry of allylboronic acids, boronates, and trifluoroborate salts in recent decades [1–6]. The derivatives of allylboronic acids are almost deprived of the above-mentioned drawbacks: they are low sensitive to air oxygen (except for allylboronic acids and boroxines in the pure form) and water (alcohols), compatible with many functional groups and can be used in different catalytic reactions. At the same time, a fundamental disadvantage of these compounds is their low reactivity associated with the reduced Lewis acidity of the boron atom, which is compensated by the intramolecular donation of electrons by the oxygen atoms (Scheme 1). The second problem is the low atom efficiency. In the case of commonly used pinacol esters, the ballast component can reach 75%! Both of these factors require the use of an excess of allyl boronates in reactions, which leads not only to a rise in the process cost but also to an increase in the boron content in wastes. Although boron is a necessary microelement for humans [19], its content in water is strictly regulated. In particular, the content of boron in potable water is limited to 2.4 mg/L [20], whereas the requirements for the boron content in water used in agriculture are even more severe. Due to the high toxicity of boron for many plants, its content is limited to 0.3 mg/L. Apparently, the use of uneconomical allyl borate derivatives in industry or pilot synthesis is unlikely and requires substantial costs for the extraction of boron from water wastes. Hence, allylic triorganoboranes (triallylboranes) are preferred for wide use, and there is a fundamental problem to make these reagents more available, safe, and selective.

One of the potential ways of addressing this issue is to convert free allylboranes to amine complexes, analogously to the widely used donor-acceptor complexes of borohydrides or trialkylboranes. The adducts of boron hydrides with different amines find extensive application in reduction and hydroboration but of particular interest is an ammonia adduct of borane (amine-borane), which is considered as a versatile basis for the storage of molecular hydrogen [21–23]. The amine adducts of trialkylboranes are used as initiators of low-temperature radical polymerization [24] and effective propellants [25, 26]. At the same time, the adducts of allylboranes are scarcely studied. Their chemical properties can be described by two common types of reactions: dissociation, which proceeds with the cleavage of the B–N bond, and protodeallylation, which proceeds with the cleavage of the С–B bond (Scheme 2).

Scheme 2. Decomposition routes of the amine adducts of allylboranes.

The first type is common with the amine adducts of trialkylboranes, which consistent pattern of regularities were studied by Brown as early as the 1940s [27–31]. He showed that the strength of the amine adducts of trialkylboranes depends both on the nucleophilicity of amines (inductive effects of substituents) and on the mutual influence of steric factors in the final complex. For example, for the least sterically hindered compound Me₃B, the stability order of the adducts is as follows (the bracketed values represent the dissociation enthalpies of the B–N bond in kcal/mol) [27]: Me₂NH (19.26) > MeNH₂ (17.64) > Me₃N (17.62) > NH₃ (13.75), which corresponds to the basicity order of the amines towards proton (the Broensted acids). At the same time, for t-Bu₃B this order changes to MeNH₂ > NH₃ > Me₂NH > Me₃N [28] according to the changes in the steric surrounding of the B–N bond. The ammonia adducts of trialkylboranes, which are used in radical polymerization, are poorly stable. Many of them are pyrophoric and, as a rule, decompose to components during isolation in the pure form [32–34]. There are a bunch of complexes of trialkylboranes with aliphatic amines that can decompose in a controlled manner; therefore, these systems are used as initiators for the polymerization of alkenes [35, 36]. It should be emphasized that, among the Lewis bases, amines are the most efficient and convenient binding agents for trialkylboranes because ethers or dialkyl sulfides or selenides do not form stable complexes with trialkylboranes [37]. In the case of phosphines, the strongest complexes are those with alkylphosphines, which are comparable in stability to the trialkylamine derivatives [38, 39]. At the same time, alkylphosphines are highly sensitive compounds on their own and are not attractive as stoichiometric reagents.

Triallylborane as the most typical representative of allylic triorganoboranes forms rather stable adducts with a range of tertiary amines, some of which can be even distilled in vacuo without decomposition. However, the processing with alcohols or water leads to the decomposition of these complexes with the release of propylene [40], except for the adducts with pyridine and its β- and γ-substituted derivatives [41]. The interaction of triallylborane with primary and secondary amines and ammonia studied in 1961 by Mikhailov and Tutorskaya [42] proceeds through the protodeallylation and affords amino(diallyl)boranes (Scheme 2), although it proceeds through the intermediate formation of the adducts. The amine adducts of cyclic allylboranes, namely, 3-borolenes demonstrate similar reactivity patterns. In the adduct of 1B-Me-3-borolene and Ме₃N, the latter readily dissociates due to exchange processes [43], whereas, in the adduct of 1B-Ph-3-borolene with Me₂NH, the amine is strongly bound with the boron atom so that an attempt to isolate the free borane under the action of the Lewis acids or an ether solution of HCl leads to the ring opening and decomposition of allylborane [44]. Hence, the sporadic data reported earlier unambiguously indicated the lability of the adducts of allylic triorganoboranes with ammonia and amines, which is likely to explain their insufficient exploration degree. Furthermore, the amine adducts have never been considered as specific reagents for allylboration.

To fill in this gap, a series of the adducts of allylic triorganoboranes were synthesized in the individual forms and studied for their properties [45–47]. It was revealed that the adducts of allylboranes with sterically unhindered primary and secondary amines are efficient allylborating reagents featuring unique properties that combined the high activity and atom economy of neat allylic triorganoboranes with the stability, safety, and selectivity of boronic acid derivatives. This implies that almost all the drawbacks of allylic triorganoboranes were eliminated.

The synthesis of the amine adducts is usually carried out by passing gaseous amines through solutions of allylic boranes or simply by mixing the reagents upon moderate cooling (Scheme 3).

Scheme 3. Synthesis of the amine adducts of triallylborane.

Unlike free allylboranes, which are incompatible with proton media, the amine adducts of triallylborane show high stability in alcohol solutions. In particular, the half-life of the ammonia adduct of triallylborane (Scheme 2, R¹ = R² = H) in 7 M methanol solution of ammonia at 60 °C is 24 h, and that at 25 °C is 36 days, whereas at –18 °C this adduct can be stored in a solution for months. In general, the order of stability of triallylborane adducts in МеОН established by our research group (based on the ¹¹B NMR spectroscopic data) corresponds to the order of stability of these adducts defined by Brown for t‑Bu₃B [28]. These compounds are low sensitive to air oxygen, water, and alcohols and are compatible with most of the functional groups. The adducts fully retain the reactivity and stoichiometry of triallyl derivatives which is intrinsic to free boranes! We explored most comprehensively the reactivity of TABA adduct, which reacts with a broad spectrum of carbonyl compounds in the presence of ammonia, resulting in the corresponding homoallylamines. Some examples of the latter are depicted in Scheme 4. Whereas ammonia affords primary amines, linear alkylamines yield secondary homoallylamines, for example, TABMA affords corresponding N-methylhomoallylamines. This process is characterized by high selectivity relative to the carbonyl groups, leaving other functionalities intact (Hal, NO₂, COOR, alkynes, pyridines, indoles, furans, etc.).

Scheme 4. Aminoallylation of carbonyl compounds with the ammonia adduct of triallylborane.

The amine part of the adduct can be either included or not in the product, depending on its structure. In particular, the dimethylamine adduct of triallylborane (TABDMA) can serve as a versatile reagent because dimethylamine is not able to take part in the aminoallylation and can be substituted for other primary amines and ammonia (Scheme 5).

Scheme 5. Aminoallylation through the amine exchange reactions.

The presence of the amine component in the adduct significantly changes the physical characteristics of the allylborane moiety, converting a sensitive borane to a stable and safe reagent that can be handled even by low qualified personnel. In addition, the adducts acquire even more unusual properties allowing for calling them as smart allylborating agents. First of all, this is the phenomenon of selectivity that is connected not only with the functional groups but also with different types of amines that take part in the aminoallylation reactions. In particular, branched primary and secondary amines do not enter aminoallylation. For example, the allylation of the imine derived from benzaldehyde and isopropylamine in methanol leads exclusively to a phenyl-substituted homoallylalcohol rather than a homoallylamine. Such a differentiated interaction enables selective aminoallylation of carbonyl groups (except for formaldehyde) only with linear amines and ammonia in the presence of other branched amines. Secondly, the amine adducts demonstrate the dynamic behavior of the borane components in methanol. This effect was revealed in the homoallylation of primary amines with formaldehyde (Scheme 6).

Scheme 6. Dynamic behavior of the adducts in reactions.

The treatment of the dimethylamine adduct of trans-cinnamyl(dipropyl)borane with linear (allylamine) and branched (α-phenylethylamine) amines affords stereochemically different products. The reaction with allylamine furnishes a linear trans-homoallylamine (74%), whereas the reaction with α‑phenylethylamine yields two products: linear (22%) and branched (54%, dr (diastereomeric ratio) 2.5:1). The latter is an expected product that arises due to a single allylic rearrangement [R] (Zimmerman–Traxler TS, see Scheme 1), while the linear trans-amines are the products of a double allylic rearrangement [RR]. It should be emphasized that the double rearrangement indicates the permanent allylic rearrangement, which is characteristic of only free allylboranes since it requires an unoccupied p-orbital at the boron atom. This version can be realized in the adducts only upon dynamic exchange of the amine ligand by the S_N1B dissociative mechanism (Scheme 6) [48, 49]. Interestingly, MeOH and water fail to protonate free allylborane. The observed phenomenon of stereochemical lability of the adducts offers opportunities for the rational design of the structures of these reagents in order to reach regio- and diastereoselective alkenylation. In contrast, the alkenyl group in the derivatives of boronic acids is stereochemically inert; therefore, the diastereoselective alkenylation requires the application of isomerically pure allylic boronates [50–52]. trans-Crotyl boronates afford anti-isomers in reactions with imines, while cis-boronates yield syn-isomers with the high diastereoselectivity (dr > 20:1) and enantioselectivity (er (enantiomeric ratio) up to 99:1) upon application of a chiral catalyst (Scheme 7) [50].

Scheme 7. Diastereoselective alkenylation with isomeric crotyl boronates.

The amine adducts can be successfully used in catalytic reactions. In particular, we accomplished efficient catalytic allylation of imines with copper(I) phosphine complexes [45]. Presumably, other metal salts, which were used in the reactions of allylboronic derivatives, can also be utilized [53]. The preliminary data on the activity of the amine adducts in Cu(I)-catalyzed allylation of imines revealed unprecedented activity that cannot be compared with those of the boronate derivatives. Undoubtedly, this field is now extremely competitive and our research group thoroughly explored it.

Promising application fields of the amine adducts

Almost the only one catalytic process where allylic triorganoboranes have been used earlier is the coupling with (het)aryl-, vinyl halides, and triflates in the presence of palladium phosphine complexes [54–61] under the modified conditions of the Suzuki–Miyaura reaction (Scheme 8) [62].

Scheme 8. Catalytic couplings of allylboranes.

Without going into details of the coupling process, several important features of the reaction merit special mentioning. First, the allyl group transfer to the palladium catalyst proceeds through an anionic borate complex that stabilizes even easily protolized boranes, such as tricrotylborane [55] and B-allyl-9-BBN [57]. Second, the groups sensitive to allylboranes, such as ketones, esters, amides, pyridines, and, in some cases, even aldehydes, remain intact during the coupling [59]. Third, the use of chiral phosphine and phosphite ligands allows one to accomplish the process in an enantioselective manner (ee (enantiomeric excess) 82%) [61, 62]. In this respect, the amine adducts of allylic triorganoboranes developed by our group are of paramount interest for the catalytic coupling as less sensitive but highly active reagents. The synthesis simplicity and high atom efficiency make the adducts of triallylboranes good candidates for the relevant industrial application. The resulting terminal alkenes can be used in organic synthesis and as monomers for functionalized polymeric materials.

The promising route of application of the amine adducts of allylic triorganoboranes is the construction of BN aromatic heterocycles [63, 64]. The CC/BN isosterism strategy allows for substantial expansion of the chemical scope of carbon compounds. Benzene and related aromatic compounds as conventional and popular moieties in drugs, polymers, and functional materials are presented in the form of an analogous series of BN isosters: 1,n-dihydro-1,n-azaborines or simply 1,n-azaborines (n = 1–3) (Scheme 9). These BN heterocycles have a variable degree of aromaticity and stability: the most thermodynamically stable compounds are 1,2-azaborines, the least stable compounds are 1,3-derivatives. The delocalization of π-electrons has a reverse tendency: the most aromatic structure is typical for 1,3-azaborine, whereas 1,4-isomer is the least aromatic derivative [65].

Scheme 9. Mono- and polycyclic 1,2-azaborines.

Azaborines can be both monocyclic and included in polyaromatic molecules such as BN naphthalenes, phenanthrenes, tetraphenes, and so on (Scheme 9) [66–70]. The location of substituents in the ring relative to the BN moiety does not affect significantly the stability and aromaticity, except for the addition of substituents directly to the boron or nitrogen centers. In this case, the difference in free energies of B-/N-isomers reaches 40–50 kcal/mol [71]. The investigation of the polymerizations of isomeric СС/1,2-BN styrenes showed that the distribution of charges in the conjugated vinyl group of monomers and the dissociation energy of bonds in the corresponding alkyl fragment of polystyrenes are almost identical and do not depend on the position of the BN moiety. At the same time, the glass transition points of BN polystyrenes is considerably higher than those of their СС analogs (Scheme 10) [72], while the absorption and emission bands in the UV-vis spectra of the BN heterocycles are located, as a rule, in the longer wave region relative to those of the СС isosters and feature unusual characteristics [72, 73]. Consequently, the synthesis of the BN isosters represents an important method for tuning the electronic and physical characteristics of molecular systems. It was shown that BN arylphosphine ligands possess essentially higher donor ability than the analogous СС ligands (Scheme 10) [74]. These properties open the way to a new direction in the design of ligands with improved electronic properties.

Scheme 10. Effect of the BN moiety on the physical properties.

An extremely important direction of the development of the BN isosterism concept is an idea to substitute СС, СN, or CO (hetero)aromatic moieties for BN analogs in the molecules of biologically active compounds and drugs. Since the highest stabilities among azaborines are demonstrated by the 1,2-derivatives, they seem to be the most promising candidates for application in biological objects. Unlike the phenyl group which has a zero dipole moment, 1,2-azaborines are much more polar (the dipole moment is 2.1 D). This along with their ability to form hydrogen bonds lead to an increase in the solubility of azaborine derivatives [75]. Earlier it was shown that 1,2-dihydro-1,2-(diethyl)azaborine binds with a hydrophobic pocket T4 of lysozyme analogously to benzene and 1,2-diethyltoluene, retaining the chemical stability upon interaction with proteins [76, 77]. A BN isoster of a cyclin-dependent kinase (CDK2) inhibitor [78] appeared to be more efficient than its СС analog almost in 4 times (Scheme 11) [79]. The improved characteristics included also the pharmacokinetic parameters (in a rat model) such as the lower clearance and higher bioavailability and half-life of the BN-CDK2 inhibitor. Recently, a BN analog of tryptophan (BN-Trp) was synthesized in order to obtain surrogate peptides [80]. The potential biocompatibility of these proteins was studied by the absorption of BN-Trp with an auxotrophic strain of Е. coli [81]. It was found that BN-Trp does not inhibit the growth of bacteria but is consumed almost ten times worse than the natural amino acid. This result shows that BN-Trp is an appropriate substrate for endogenous tryptophanyl-tRNA synthetase. The investigations on the introduction of BN-Trp into a fluorescent protein sfGFP confirmed the compatibility of the surrogate amino acid with tryptophanyl-tRNA synthetase. Another report showed that the properties of BN naphthalene isosters of propranolol β-blocker have close pharmacological characteristics with the improved metabolic stability in microsomal cells of human liver and more efficient inhibition of cytochrome systems P450 2D6 and 1А2 (Scheme 11) [82].

Scheme 11. Effect of the BN moiety on the pharmacological properties.

The thiophene derivatives of diazaborines were synthesized that efficiently inhibit human neutrophil elastase which refers to serine proteases—a potential target for the treatment of associated inflammatory diseases, such as rheumatoid arthritis, bacterial and viral infections, cancer, and Alzheimer's disease [83].

The strategy of BN isosterism is new in medicinal chemistry. Nowadays, there are insufficient data for the comprehensive evaluation of its advantages and the most efficient directions for application. However, the approach in itself is productive and, of course, interesting for further investigation. An important role can be played by the well-developed calculation methods, which enable the prediction of the most significant changes in electronic characteristics upon substitution of carbon aromatic moieties for BN isosters.

The realization of all these directions requires efficient methods for the synthesis and modification of BN heterocycles. There are different approaches based on the reactions of electrophilic borylation of aromatic rings [84] and metathesis cyclization of allylic aminoboranes (Scheme 12) [85, 86]. The latter is the softest and fastest method for the formation of an azaborine core.

Scheme 12. Methods for the synthesis of BN heterocycles from allylic aminoboranes.

The starting diene systems for the metathesis cyclization of aminoboranes are obtained from allyldichloro- and diallylchloroboranes via the corresponding amine adducts. Earlier our research group has developed the most straightforward and efficient method for the synthesis of allylated chloroboranes from the corresponding organoboranes and BCl₃ by an exchange reaction (Scheme 13, reaction 1) [14]. Along with the free aminoboranes, the synthesis of haloallylboranes can also be accomplished from the amine adducts, which can be generated in situ under the action of BCl₃. An additional equivalent of boron chloride will be consumed for the amine binding, which in the case of a hydrocarbon solvent can be separated by the precipitation (Scheme 13, reaction 2). The synthesis of a tetraallyl derivative can be readily accomplished by simple heating of the adduct of triallylborane with diallylamine (Scheme 13, reaction 3). Furthermore, this can be achieved also by the exchange reaction between dimethyl- and diallylamines. Since the amines are exchanged dynamically, under appropriate conditions volatile dimethylamine (bp 7 °С) will be fully removed from the reaction sphere. Of particular importance is the problem of production of С-substituted 1,2-azaborines. This can be realized using substituted cinnamylboranes and the corresponding allylamines (Scheme 13, reaction 4). In this case, the phenyl group will stabilize the depicted regioisomer owing to the С=С conjugation, and the metathesis cyclization will afford the target C-substituted aminoborane and styrene.

Scheme 13. Synthetic routes to aminoboranes from the amine adducts.

Therefore, the amine adducts of allylic triorganoboranes can serve as efficient reagents for the synthesis of BN heterocycles. Along with the described methods for the synthesis of BN systems, the methods for the functionalization of the resulting boracycles were also developed (Scheme 14) [87].

Scheme 14. Examples of the methods for functionalizing 1,2-azaborines.

Being aromatic heterocycles, they readily enter the typical electrophilic substitutions: halogenation, acylation, nitration, aminomethylation, and catalytic CH activation. Another type of direct functionalization includes the process of nucleophilic (С, N, O, S, and P nucleophiles) and electrophilic substitution at the boron and nitrogen atoms. Furthermore, the system of conjugated C=С bonds can enter [4+2] cycloaddition with activated dienophiles by the Diels–Alder reaction. A large class of palladium-catalyzed cross-couplings (the Suzuki, Kumada, and other reactions) and different couplings on nickel can completely adopt the chemistry of BN isosters to the already developed transformations.

Other important products of allylboration are homoallylamines which can be obtained by the allylation of CN multiple bonds of imines, nitriles, NH-containing amides, and aromatic azaheterocycles [4]. Homoallylamines are extremely popular in pharmaceutical chemistry and synthesis of alkaloids and different heterocyclic compounds [88–91]. The diverse catalytic transformations of homoallylamines were discovered [92–100] that demonstrate their high synthetic potential.

Earlier our research group has developed the methods for synthesis of several alkaloids, namely, cephalotaxine [101] and hippocasine (Scheme 15) [102]. The former is a key component of homoharringtonine alkaloid (Synribo®), which is effective against kinase inhibitor-resistant forms of chronic myeloid leukemia. The latter is included in the composition of azaphenalene defensive alkaloids of Coccinellidae, which biological activity is associated with the effect on the central nervous system of animals but is underexplored [103]. The starting compounds for both synthesized alkaloids were heterocyclic homoallylamines obtained using neat allylboranes. The synthetic scheme for these compounds using the amine adducts (for example, TABDMA) will be safer and, undoubtedly, is of particular interest for the production of these important molecules (Scheme 15).

Scheme 15. Tentative synthetic routes to heterocyclic homoallylamines via an exchange reaction of TABDMA
for the production of alkaloids and plant growth stimulators.

Recently, new efficient plant growth stimulators with potential safener properties were discovered that contain α,α'-diallylated tetrahydropyridine moieties and, thus, serve as the analogs of dichlormid commercial safener [104], which can also be synthesized using the amine adducts.

Starting from homoallylamines, a general synthetic methodology for piperidinone heterocycles of diverse structures was developed, including 6-substituted piperidine-2,4-diones and 2,6-substituted 6-amino-2,3-dihydro-4-pyridine(thi)ones (Scheme 16) [105–108]. The synthesis of homoallylamines by the aminoallylation with the amine adducts of triallylborane is well developed (see Schemes 4 and 5).

Scheme 16. Synthesis of piperidinone heterocycles from homoallylalimes via enolate rearrangements. Examples of biologically active piperidinones.

The key elements of this transformation are enolate rearrangements of isocyanate and carbodiimide types, which proceed through cyclic enol ethers under the action of potassium tert-butoxide (Scheme 16). Piperdinone heterocycles serve as a versatile basis for the creation of a whole range of drugs with modern types of activities [109]. Scheme 16 illustrates the following examples: (a) inhibitor of human lactate dehydrogenase А (LHDA) GNE-140 which is used for the treatment of glycolysis-dependant tumors and is most active against pancreatic cancer; (b) inhibitors of Cdc7 serine/threonine kinase which induce cancer cell apoptosis through reversible blocking of cell proliferation in primary fibroblasts; (c) inhibitors of Pim serine/threonine kinases. In healthy tissues the expression of the so-called Pim proteins is insignificant; however, in hematologic and solid tumors including multiple myeloma, acute myeloid leukemia, prostate cancer, stomach and liver carcinoma, there is observed a significant increase in the level of Pim proteins. Therefore, the inhibition of Pim kinases is a promising route to cure Pim-associated cancers. Yet another promising drug for cancer treatment are inhibitors of heat shock protein 90 (HSP90) (d). In specific cases, the level of HSP90α in cancer cells can increase up to 10 times relative to that in healthy cells [110]. The HSP90 chaperone proteins service over 400 cell client proteins that is why the HSP90 inhibitors are important therapeutic targets.

The role of synthetic processes in the development and production of drugs is extremely important from the viewpoint of many parameters [111, 112]. Therefore, new allylborating reagents that would be able to improve the process of creation of these drugs are highly desirable.

Conclusions

It can be concluded that the amine adducts of allylic triorganoboranes have enormous potential in organic and organoelement synthesis for the production of new drugs, natural products, and materials with valuable properties. The key factors for the choice of these boron derivatives are their stability, safety, and atom economy. The change of the product types depending on the composition of a reaction medium allows one to attribute these compounds to smart reagents, and these properties require further detailed analysis. The reactions of catalytic allylation with the amine adducts of allylic triorganoboranes have much room for development. These investigations can update and advance whole directions of organoboron synthesis.

The production of BN aromatic heterocycles is a separate rapidly developing research area. The concept of СС/BN isosterism considerably expands the chemical scope of carbon compounds, affording sterically identical molecules with new opto-electronic properties and pharmaceuticals with improved characteristics. The use of the amine adducts of allylic triorganoboranes in this field can provide facile and simple access to aromatic BN heterocycles, encouraging more efficient development of this direction.

Acknowledgements

This work was supported by the Ministry of Science and Higher Education of the Russian Federation.

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