1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
A Straightforward Access to Stable b-Functionalized Alkyl
Selenols
Damiano Tanini,
a,* Caterina Tiberi,
aCristina Gellini,
aPier Remigio Salvi,
aand
Antonella Capperucci
a,*
a Dipartimento di Chimica “Ugo Schiff”, Via della Lastruccia 3-13, 50019 Sesto Fiorentino (FI), Italy.
Phone: + 39 055 45735-50/-52 fax + 39 055 4574913
E-mail: damiano.tanini@unifi.it; antonella.capperucci@unifi.it
Received: May 8, 2018; Revised: June 22, 2018; Published online: July 17, 2018
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.201800602 Abstract: Treatment of epoxides with bis(trimethylsilyl)-selenide under strictly controlled conditions allows to isolate b-hydroxy selenols which evidence an unexpected stability, taking into account their known propensity to afford diselenides. Also thiiranes and aziridines lead to functionalized selenols bearing a thiol and a N-Ts- or N-Boc-protected amino moiety on b-position. These selenols were stable enough to react with different electrophiles. Ainitio DF calculations on two suitable model systems, n-propyl selenol and b-hydroxy derivative, allow to ascribe the observed low tendency to oxidation to noncovalent interactions between the selenol moiety and theOH group.
Keywords: Bis(trimethylsilyl)selenide; Regioselectivity; Ring-opening; Selenols; Small ring systems
Introduction
Selenium containing compounds play an important role in different fields of chemistry,[1] biochemistry[2] and materials science.[3]The use of organic derivatives of selenium has recently faced a strong development, due to the fact that several compounds of this class have been demonstrated to be versatile reagents in organic synthesis.[4] They have also been used to obtain different biologically active compounds, for example antioxidants and GPx mimics.[5]
Among the variety of organoselenium compounds, aryl selenols[6]are of particular interest for their use in catalysis, in coordination and inorganic chemistry.[7] As a prominent example aryl selenols take part in asymmetric transformations catalyzed by chiral com-plexes.[8] Studies are also reported about alkanesele-nols[9] able to catalyze thiol-disulfide interchange reactions, thus showing interesting applications.[10] Alkylselenol (and the parent Alk2Se2) formulations have been described for the treatment and prevention of cancer.[11]
Nevertheless, their use is significantly limited due to the difficulty in their preparation for the high instability, mainly concerning the aliphatic series.
Due to quick decomposition, they are usually generated in situ from diselenides and selenocyanates
by treatment with reducing agents.[9a,d,12] Reactions of elemental selenium with Grignard reagents and HCl[9e,13] or with NaBH4 (to generate NaSeH) have been also proposed to obtain selenolates.[9a,c,14] It is in fact described that SeH is one of the most easily oxidized functional groups.[9a,e,15] Air or oxygen are able to convert in high yield selenols into the corresponding diselenides, especially under basic con-ditions. As a result, relatively few synthetic studies have been reported. To the best of our knowledge a limited number of b-substituted selenols, which are the focus of the present study, have been obtained, either through a multistep procedure by reductive cleavage of Se-oligomers[12d,16] or via ring opening of epoxides with hydrogen selenide.[17] However in these studies alkyl selenols were formed in rather low yield, diselenides being usually the products in the largest percentage.[14a,16,17] Thus, the study of functionalized aliphatic selenols represents an interesting challenge both from a synthetic point of view and for their possible applications. It appears desirable to under-take a synthetic strategy favoring b-substituted sele-nols over diselenides.
Our long-standing interest in the study of organo-silicon compounds led us to disclose a protocol for the synthesis of b-mercapto alcohols through a regio- and stereoselective ring opening of epoxides with bis
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
(trimethylsilyl)sulfide.[18] More recently the interest was focused on the less explored selenium analogue, bis(trimethylsilyl)selenide (hexamethyl-disilaselenane, HMDSS). Our preliminary findings showed that HMDSS acts as an efficient reagent with epoxides, under TBAF or PhONnBu
4 catalysis, to afford b-hydroxydiselenides,[19] arising from oxidation of the parent selenols. It remains an open question whether the reaction path may be freezed at the intermediate step by a judicious choice of the external parameters determining the course of the reaction. Several attempts to isolate the selenol intermediate failed under the reported conditions. On the other hand it is known that not only the nature of the precursors but also the experimental conditions are crucial to isolate organo-selenols which, in the absence of a substantial stabilization, are typically unstable compounds.
In this communication we wish to report on our recent results aimed at the direct synthesis of a representative series of b-functionalized selenols fea-turing an unexpected stability with respect to previ-ously described alkyl selenols.
Results and Discussion
Synthesis of b-substituted selenols
On the basis of our foregoing results to synthesize selenides and diselenides,[19b] the reaction of epoxides with HMDSS 1 was carefully re-examined in order to search for the suitable way to isolate b-hydroxysele-nols. A systematic investigation was undertaken and a reaction screening was carried out treating 2-[(ally-loxy)-methyl]oxirane 2 a with HMDSS under different experimental conditions by varying the temperature, the amount of catalyst and the reaction time. The results are shown in Table 1.
We found that the reaction time, intended as the time at which the reaction is stopped by addition of citric acid, and the temperature were the main parameters to avoid oxidation of 3 a to diselenide 4 a. Reactions carried out at room temperature for 20 min or 10 min led to the formation of diselenide as exclusive or major product (Table 1, entries 1–2). Lowering the temperature from r.t. to 0 8C or 15 8C the 3 a:4 a ratio (determined by proton NMR) in-creases, thus avoiding more efficiently the oxidation step 3 a!4 a. Finally, the amount of catalyst was also adjusted for best results. Through a fine tuning of these parameters the desired b-hydroxyselenol 3 a was obtained as major product either at 0 8C or at 15 8C under inert atmosphere with 20% TBAF[20] (Table 1, entries 4 and 6, respectively). The 2 a conversion efficiency and the yield of 3 a were higher in the first than in the second case. Treatment with other proton sources such as NH4Cl and HCl was performed during the work up, but a lower selenol/diselenide ratio was
obtained. The procedure was extended to a series of substituted epoxides leading to the class of 2-sub-stituted 2-hydroxy selenols 3 a–d according to the Table 2.
The reactivity proved general, allowing the syn-thesis of 2-substituted 2-hydroxyselenols bearing dif-ferent moieties. In summary, the reaction is (a) opera-tionally simple, (b) highly regioselective, i. e., only the product obtained by the attack on the less hindered side of the epoxide is observed in the crude and (c) allows to isolate the selenols pure enough to be used without any further purification.
Due to the mildness of the experimental condi-tions, the glycidol ring in 2 a–c (2 b: R=CH2OBn, 2 c: R=CH2O(p-OMe-C6H4)) was reacted with preserva-tion of the protective moieties, and, more interestingly, the chiral center of the enantiopure glycidol (R)-2 b is retained in the b-hydroxyselenol (S)-3 b. Also, in the presence of a second center prone to nucleophilic attack, like the chloride termination in epichlorohy-drin 2 d (R=CH2Cl), the reaction is directed exclu-sively toward the epoxide skeleton affording 3 d, thus conserving the regioselectivity for this class of reac-tions. Besides TBAF, also tetrabutylammonium phenoxide (PhONnBu
4) was efficient in promoting the ring opening of epoxides, leading to hydroxy selenols in comparable yields. In this case phenol is formed as by-product, and the subsequent purification inevitably leads to oxidation of the selenol.
Aiming at evaluating the limits and the potential of this methodology, we extended this strategy to differ-ent ring strained compounds, such as thiiranes and Table 1. Optimization of reaction conditions for the syn-thesis of b-hydroxy selenols.
[a]Ratio determined by1H NMR.
[b]Consumption of SM 2 a determined by1H NMR of the
crude.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
aziridines. 2-(Allyloxymethyl)-thiirane 5 a was treated with (Me3Si)2Se in the presence of a catalytic amount of TBAF under different conditions (Scheme 1). The reaction was originally carried out under the same conditions as for the ring opening of epoxides (0 8C, 10 min, 20% TBAF) but a complex mixture of products was found, probably arising from undesired polymerization reactions, together with a small
amount of selenol (6 a):diselenide (7 a) in a ca. 1:1 ratio. Thus, a lower temperature was considered (15 8C), allowing to obtain selenol 6 a in ca. 5 min as the major product (Scheme 1).
With a longer reaction time (20 min) the reaction was less selective (6 a:7 a ca. 60:40), whereas with a treatment at lower temperature (30 8C) for 30 min the conversion of the starting episulfide 5 a decreased (ca. 40%) and the ratio 6 a:7 a was reduced (~ 35:65). A variety of b-mercapto selenols 6 a–c, which bear both the SH and the SeH functional groups, were isolated in high yields (see Table 2). In this respect it is remarkable that both groups, although highly oxidiz-able moieties, survive in the products thanks to the mildness of the synthetic strategy. The synthesis can be extended to chiral substrates leading to optically active 1,2-hydroselenothiol (S)-6 b (Table 2).
As to aziridines, the reaction was further refined by slightly modifying the reaction conditions. In fact Table 2. Synthesis of b-hydroxy, b-mercapto- and b-amino selenols.[a]
[a]Reaction conditions: Ring opening of epoxides: TBAF (0.20 eq.), 0 8C, 10 min. Ring opening of thiiranes:TBAF (0.20 eq.),
15 8C, 5 min. Ring opening of N-Ts aziridines: TBAF (0.33 eq.), 0 8C, 5 min. Ring opening of N-Boc aziridines: TBAF 81.60 eq.), r.t., 60 min.
[b]Less than 10% of diselenide was formed.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
treatment of N-Ts-aziridine 8 a under epoxide and episulfide conditions, though favoring a high conver-sion (> 95%), led to a rather low selenol (9 a) : diselenide (10 a) selectivity (20:80 and 65:35, respec-tively). Increasing the catalyst amount to 30% and carrying out the reaction for a time as short as five minutes at 0 8C a noticeably high ratio of selenol 9 a: diselenide 10 a was reached (> 95:5) (Scheme 2, Con-ditions A). As in the epoxide and thiirane case, b-amino selenols 9 a–d (see Table 2) arise from the regio- and stereoselective attack of HMDSS on the chiral aziridines (obtained from natural amino-acids) so that the optical purity of the chiral reagent is preserved. The less activated N-Boc aziridines 11 a, b required a longer reaction time, a higher temperature and a larger amount of catalyst to promote the transformation (Scheme 2, Conditions B). Thence 11 a and 11 b were treated with HMDSS in the presence of 1 equivalent of TBAF at r.t. for 1 hour and the corresponding N-Boc b-amino selenols (12 a, b, Ta-ble 2) were obtained in good yield.
The formation of the b-functionalized selenols in the three series of compounds was unambiguously supported by 1H and 77Se NMR measurements. The characteristic resonance frequencies are reported in Table 3.
The proton on the selenium atom (SeH) is strongly shielded and has a typical resonance frequency between 0.4 and 0.9 ppm.[9d] 77Se resonance is shifted upfield to 40/90 ppm. The 1J
SeH coupling constant measured on the coupled proton spectrum (natural abundance of 77Se: 7.63%) resulted 45 Hz. Ab-initio DF calculations
The stability of the b-substituted selenols has come much as unexpected since it is generally known that selenols are unstable systems, quickly undergoing oxidation to diselenides. It is therefore worth acquir-ing a deeper insight into these structures in relation to the hydrogen bond interaction between the selenol moiety and theOH, SH, NH groups.
A number of papers have appeared in recent years pointing to the importance of noncovalent interactions in molecular systems containing selenium.[21]The role of intramolecular interactions in organoselenium com-pounds has been reviewed.[21c] Also, strong Se···HN hydrogen bonds have been reported in proteins with selenomethionine residues.[21a]A thorough sampling of protein crystal structures has revealed that for many of them the Se···H distances are within the sum of van der Waals radii, 3.1 A˚ , thus indicating attractive interactions. In two cases, human inositol 1,4,5-triphosphate 3-kinase and phosphoethanolamine N-methyltransferase, detailed DF calculations on inter-acting peptide groups surrounding the Se···HN frag-ment were performed, predicting Se···H distances of 2.367 and 2.676 A˚ , respectively. Hydrogen bonding in neutral dimers of H2Se with H2O, H2S and H2Se has been studied with highly refined computational meth-ods.[21b] Two dimeric structures have been determined for the H2Se···H2O dimer, one with a linear SeH···O
Scheme 2. General scheme for the synthesis of b-amino selenols.
Table 3. Typical NMR absorption range of b-functionalized selenols.[a]
[a]Specific values for each R are described in Experimental
Section.
[b]Ref. CDCl
37.26 ppm. [c]Relative to Ph
2Se2(461 ppm).
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
triatomic geometry and H···O distance of 2.191 A˚ and a second with a weakly bent Se···HO arrangement with Se···H distance of 2.718 A˚ . In addition, in the H2Se···H2Se dimer the Se···HSe geometry is linear and the Se···H distance amounts to 3.019 A˚ .
Encouraged by these reports we have performed ab initio DF calculations at B3LYP/6-311G + + (p,d) level of theory with the Gaussian09 suite of pro-grams[22] on two isolated model systems, n-propyl selenol (I, CH3CH2CH2SeH) and the b-hydroxy deriv-ative (II, CH3CH(OH)CH2SeH). The conformational energy was evaluated as a function of the Se-CCCH3 torsional angle scanning the 3608 angular range every 308 and optimizing the geometrical structure at each angle. The two sets of calculations are compared in Figure 1 together with an interpola-tion of the calculated points by using a spline funcinterpola-tion.
For both molecules the energy minima are associ-ated with the anti and the two gauche conformations, as expected; however the energy barriers are appreci-ably higher for II than for I. As to II, it should be also noted that in the anti and in one of the two gauche conformations the O1H6···Se5 distance amounts to 2.73 and 2.82 A˚ , respectively, in good agreement with ref. [21b]. Thus the result may be confidently
inter-preted as due to the hydrogen bond interaction stabilizing II over I.
Further, it was inquired about the occurrence of dimer association. Being II a chiral molecule, in principle two units of II can be paired by H-bond interactions, to form dimeric-like structures of type SR, RS, SS and RR, the first pair being at energy different from that of the second pair. To simplify matter, only dimers derived from anti conformers have been considered, starting from two such struc-tures arranged several A˚ distant along the x, y, z axes. As displayed in Figure 2, two dimeric structures, the first of type SR and the second of SS, have been found, both being stable as shown by the fact that all the vibrational frequencies are real. They have BSSE[23]corrected energies 2.1 and 1.6 kcal/mol lower than two isolated II molecules.
In both cases the hydrogen bond is intermolecular (see Figure 2), the SR SeH···O structure being almost linear with rH····O=2.29 A˚ while the SS O···HC structure having the OHC angle 1638 and rO····H= 2.49 A˚ . Repeating the calculation for I, only one stable dimer has been determined with corrected energy 0.74 kcal/mol lower than the two isolated molecules in the anti conformation. A weak intermolecular hydro-gen bond SeH···Se occurs, with linear SeH···Se group and H···Se of 3.18 A˚ . Our results on the two groups, SeH···O and SeH···Se match satisfactorily previous data.[21c]
On the other hand, stabilizing effects due chalc-ogen bonding interactions cannot be ruled out.[24]As a matter of fact the divalent selenium, besides the two covalent bonds, can further interact non-covalently Figure 1. Conformational energy (DE, kcal/mol, full squares,
DF/B3LYP/6-311 + + (p,d) results) as a function of the
tor-sional angle SeCCCH3. Energies are calculated with
respect to that of the anti conformer. Above the minima the conformational structures are sketched with the following colors for atoms: yellow Se, red O, grey C, grey-white H. Dashed line: data interpolation (see text for details). Upper: 2-hydroxy n-propyl selenol II; lower: n-propyl selenol I with atomic numbering.
Figure 2. Dimer structures. Upper, dimer of 2-hydroxy n-propyl selenol II with SR and SS configurations, (a) and (b) respectively. Lower: dimer (c) of n-propyl selenol I. Results from ab initio DF/B3LYP/6-311**(d,p) calculations. The shortest hydrogen bond distances (A˚ ) are indicated.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
with neighboring heteroatoms such as O, S, N, being the chalcogens able to behave as both acceptor and donating atoms. Thus, in the b-hetero substituted selenols an intramolecular stabilizing nonbonded Se…
Het interaction can be considered. This hypothesis appears to be supported by the Se…O distances evaluated in structures I and II (3.28 A˚ and 3.29 A˚ for anti and gauche conformations, respectively), in agree-ment with values found when intramolecular sele-nium-oxygen nonbonded interactions are present in selenated ketones (2.84 A˚ ) and nucleosides (3.31 A˚ ).[25]
A cooperation between the above mentioned non-covalent interactions (hydrogen- and chalcogen bond) can also be taken into consideration and may contrib-ute to the stabilization of these selenated compounds. Selenated derivatives from selenols
A synthetic application of the b-substituted selenols comes from being precursors of selenated derivatives. To this purpose, a preliminary investigation was carried out with a representative series of electro-philes in order to evaluate their behaviour as nucleo-philic reagents in alkylation reactions (Table 3), following the protocol used in the thiol alkylation, i. e., treatment with alkyl halides at room temperature for few hours in the presence of Cs2CO3and TBAI.[26]
Taking into account that selenols are stronger acids than thiols, the selenolate should be formed under milder conditions than thiolates. Stirring at 0 8C the reaction mixture with Cs2CO3 and TBAI and then adding methyl iodide, the Se-methylated product 14 was isolated in good yield (68%, Table 4, entry 1), thus confirming that selenols are stable enough to be functionalized under suitable conditions. The general-ity of this procedure in the formation of CSe bonds has been checked with different electrophiles. Besides methyl iodide, the sterically more demanding isopropyl bromide was reacted with selenol 3 a under the same conditions, affording the corresponding unsymmetrical selenide 15 (Table 4, entry 2), showcas-ing the versatility of this Se-alkylation procedure with secondary hindered alkyl halides. Furthermore, when methyl bromoacetate was treated with selenol 3 a, a selective Se-alkylation led to the formation of func-tionalized b-selenoester 16 in good yields (Table 4, entry 3).
With the aim to extend the scope of the reaction, different electrophiles, such as strained heterocycles, methyl vinyl ketone and oleoyl chloride were treated with b-hydroxy selenols.
The reaction of selenol 3 a with methyloxirane smoothly afforded the unsymmetrical b,b’-dihydroxy selenide 17 in good yield (Table 4, entry 4), achieved through a regioselective ring opening reaction. Fur-thermore, when selenol 3 d was treated with aziridine
8 e, a clear regio- and chemoselective process took place, leading to the exclusive formation of the ring opened product 18, the halogen on the side chain being preserved (Table 4, entry 5).
When the methyl vinyl ketone was used in the reaction with selenol 3 b under the same conditions, the corresponding selenide 19 was isolated, even though in rather low yield, through a seleno-Michael addition (Table 4, entry 6). The selenolester 20 could be easily achieved from 3 a and oleoyl chloride (Table 4, entry 7).
With mercaptoselenols, Se-methylation of 6b oc-curred selectively with respect to S-methylation lead-ing to b-mercaptoselenide 21 (Table 4, entry 8). Similarly, once the b-amino selenol 9 a was treated with methyl 3-bromopropanoate under the same conditions, the unsymmetrical b-aminoselenide 22 was isolated in rather good yield (76%, Table 4, entry 9).
In summary, exclusive Se attack is a noticeable feature of this procedure starting from b-substituted Table 4. Reaction of selenols with selected electrophiles.
[a]Isolated yield. [b]Reaction time 6 h. [c]Reaction time 10 min.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
selenols, allowing to form polyfunctionalized struc-tures bearing different moieties.
Conclusion
In conclusion, we have developed a direct and convenient procedure to synthesize selenols bearing on the C-2 the hydroxy, mercapto and amino function-alities. Due to the mildness of the experimental conditions, labile groups on the side chain, prone to nucleophilic substitution, are preserved. These sele-nols demonstrated an unexpected stability, which can be ascribed to hydrogen bond interaction between SeH and OH groups, as evidenced by ab initio DF calculations on two selected model systems. This novel class of organoselenium compounds can be efficiently reacted with electrophiles of different nature under suitable conditions to form new CSe bonds, allowing to access various selenated derivatives.
Experimental Section
Caution! Selenols, HMDSS and hydrogen selenide are malodorous and potentially toxic compounds. All reactions and handling should be carried out in a well ventilated hood.
General procedure for the synthesis of b-hydroxyselenols 3
A solution of epoxide 3 (1 mmol) and bis(trimethylsilyl) selenide (HMDSS) 1 (1.6 mmol) in dry THF (3 mL) was cooled under inert atmosphere (N2) at 0 8C, and treated with
TBAF (0.2 mL of 1 M THF solution, 0.20 mmol). The reaction was stirred for 10 min and then solid citric acid (ca. 1.5 mmol, 290 mg) was added. The solution was diluted with diethyl ether, washed with water, and dried over Na2SO4.
The solvent was evaporated under vacuum affording a crude product pure enough to be used without further purification. As a general comment for the synthesized selenols: due to their instability at room temperature and in the presence of air: i) all the manipulations should be carried out under inert atmosphere; ii) low temperature storage (0–4 8C) under N2 is
required.
General procedure for the synthesis of b-mercaptoselenols 6
A solution of thiirane 5 (1 mmol) and bis(trimethylsilyl) selenide (HMDSS) 1 (1.6 mmol) in dry THF (3 mL) was cooled under inert atmosphere at 15 8C, and treated with TBAF (0.2 mL of 1 M THF solution, 0.20 mmol). The reaction was stirred for 5 min and then solid citric acid (ca. 1.5 mmol, 290 mg) was added. The solution was diluted with diethyl ether, washed with water, and dried over Na2SO4.
The solvent was evaporated under vacuum affording a crude product pure enough to be used without further purification.
General procedure for the synthesis of N-Tosyl b-aminoselenols 9
A solution of aziridine 8 (1 mmol) and bis(trimethylsilyl) selenide (HMDSS) (1.6 mmol) in dry THF (3 mL) was cooled under inert atmosphere (N2) at 0 8C, and treated with
TBAF (0.33 mL of 1 M THF solution, 0.32 mmol). The reaction was stirred for 5 min and then solid citric acid (ca. 1.5 mmol, 290 mg) was added. The solution was diluted with diethyl ether, washed with water, and dried over Na2SO4.
The solvent was evaporated under vacuum affording a crude product pure enough to be used without further purification.
General procedure for the synthesis of N-Boc b-aminoselenols 12
A solution of aziridine 11 (1.00 mmol) and bis(trimethylsilyl) selenide (HMDSS) (1.60 mmol) in dry THF (3 mL) under inert atmosphere was treated with TBAF (1.60 mL of 1 M THF solution, 1.60 mmol). The reaction was stirred for 1 h and then solid citric acid (ca. 1.5 mmol, 290 mg) was added. The solution was diluted with diethyl ether, washed with water, and dried over Na2SO4. The solvent was evaporated
under vacuum affording a crude product.
General procedure for the functionalization of selenols with electrophiles
A solution of selenol (1.0 mmol) in dry DMF (5 mL) was cooled under inert atmosphere at 0 8C, and treated with Cs2CO3 (326 mg, 1.0 mmol), TBAI (369 mg, 1.0 mmol) and
then with the electrophile (1.1 mmol). The reaction was stirred for 3 h and then diluted with diethyl ether (10 mL), washed with water (335 mL), brine (5 mL) and dried over Na2SO4. The solvent was evaporated under vacuum and the
crude product was purified by flash column chromatography.
Acknowledgements
D.T. and A.C. express great appreciation to the late Professor Alessandro Degl’Innocenti, whose initial contribution to this research was of considerable significance.
References
[1] For selected books and reviews, see: a) C. Santi, L. Bagnoli, Molecules 2017, 360, 2141 and references cited therein; b) T. Wirth (Ed.), Organoselenium Chemistry, Synthesis and Reactions Wiley-VCH, Weinheim, 2012; c) J. Młochowski, H. Wjtowicz-Młochowska, Molecules 2015, 20, 10205–10243; d) S. Santoro, J. B. Azeredo, V. Nascimento, L. Sancineto, A. L. Braga, C. Santi, RSC Adv., 2014, 4, 31521–31535.
[2] For selected recent reviews, see: a) V. K. Jain, in Organoselenium Compounds in Biology and Medicine: Synthesis, Biological and Therapeutic Treatments (Eds.: V. K. Jain, K. I. Priyadarsini) RSC, 2017, pp. 1–33; b) B. Banerjee, M. Koketsu Coord. Chem. Rev. 2017, 339, 104–127; c) S. W. May, in Topics in Medicinal Chemistry
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
(Atypical Elements in Drug Design), Springer Interna-tional Publishing, 2016, pp 87–118; d) M. Roman, P. Jitarub, C. Barbante, Metallomics 2014, 6, 25–54. [3] a) V. Krylova, N. Dukstiene, S. Zalenkiene, J.
Baltrusai-tis, Appl. Surf. Sci., 2017, 392, 634–641; b) J. Ossowski, G. Nascimbeni, T. Zaba, E. Verwuster, J. Rysz, A. Terfort, M. Zharnikov, E. Zojer, P. Cyganik, J. Phys. Chem. C, 2017, 121, 28031–28042 and references cited therein.
[4] a) S. Nakamura, T. Aoki, T. Ogura, L. B. Wang, T. Toru, J. Org. Chem. 2004, 69, 8916–8923; b) S. S. Khokhar, T. Wirth, Angew. Chem. Int. Ed. 2004, 43, 631–633; c) G. Pandey, S. R. Gadre, Acc. Chem. Res. 2004, 37, 201–210; d) N. Devan, P. R. Sirdhar, K. R. Prabhu, S. Chandrase-karan, J. Org. Chem. 2002, 67, 9417–9420; e) L. Eng-man, V. Gupta, V. J. Org. Chem. 1997, 62, 157–173. [5] a) K. Arai, A. Tashiro, Y. Osaka, M. Iwaoka, Molecules
2017, 22, 354; b) V. P. Singh, J.-f. Poon, R. J. Butcher, L. Engman, Chem. Eur. J. 2014, 20, 12563–12571 and references cited therein; c) B. J. Bhuyan, G. Mugesh, in Organoselenium Chemistry, Synthesis and Reactions (Ed.: T. Wirth) Wiley-VCH, Weinheim, 2012, pp. 361– 396 and references cited therein; d) S. Yoshida, F. Kumakura, I. Komatsu, K. Arai, Y. Onuma, H. Hojo, B. G. Singh, K. I. Priyadarsini, M. Iwaoka, Angew. Chem. Int. Ed. 2011, 50, 2125–2128; e) S. K. Tripathi, S. Sharma, H. B. Singh, R. J. Butcher, Org. Biomol. Chem. 2011, 9, 581–587.
[6] A. Sørensen, B. Rasmussen, S. Agarwal, M. Schau-Magnussen, T. I. Sølling, M. Pittelkow, Angew. Chem. Int. Ed. 2013, 52, 12346–12349 and references cited therein.
[7] a) D. Manna, G. Mugesh, J. Am. Chem. Soc. 2011, 133, 9980–9983; b) A. M. Spokoyny, C. W. Machan, D. J. Clingerman, M. S. Rosen, M. J. Wiester, R. D. Kennedy, C. L. Stern, A. A. Sarjeant, C. A. Mirkin, Nat. Chem. 2011, 3, 590–596; c) K. Mashima, S. Kaneko, K. Tani, H. Kaneyoshi, A. Nakamura, J. Organomet. Chem. 1997, 545–546, 345–356.
[8] J. Sun, M. Yang, F. Yuan, X. Jia, X. Yang, Y. Pan, C.
Zhua, C. Adv. Synth. Catal. 2009, 351, 920–930 and
references cited therein.
[9] a) T. Asamizu, W. Henderson, B. K. Nicholson, J. Organomet. Chem. 2014, 761, 103–110; b) V. Y. Vshivt-sev, E. P. Levanova, V. A. Grabelnykh, E. N. Sukhoma-zova, E. R. Zhanchipova, L. V. Klyba, A. I. Albanov, N. V. Russavskaya, L. M. Sinegovskaya, N. A. Korche-vin, Russ. J. Org. Chem. 2007, 43, 1561–1562; c) A. Krief, M. Trabelsi, W. Dumont, M. Derocka, Synlett 2004, 1751–1754 and references cited therein; d) E. H. Riague, J.-C. Guillemin, Organometallics 2002, 21, 68– 73 and references cited therein; e) H. H. Sisler, N. K. Kotia, J. Org. Chem. 1971, 36, 1700–1703.
[10] a) D. Steinmann, T. Nauser, W. H. Koppenol, J. Org. Chem. 2010, 75, 6696–6699; b) R. Singh, G. M. White-sides, J. Org. Chem. 1991, 56, 6931–6933.
[11] a) D. Bartolini, L. Sancineto, A. Fabro de Bem, K. D. Tew, C. Santi, R. Radi, P. Toquato, F. Galli, in: Advances in Cancer Research (Eds.: K. D. Tew, F. Galli), Elsevier, 2017, pp 1–302 and references cited therein; b) S. Misra, M. Boylan, A. Selvam, J. E. Spallholz, M. Bjçrnstedt,
Nutrients, 2015, 7, 3536–3556 and references cited there-in.
[12] a) J. S´cianowski, J. Rafalski, A. Banach, J. Czaplewska, A. Komoszyn´ska, Tetrahedron: Asymmetry 2013, 24, 1089–1096; b) J.-C. Guillemin, G. Bajor, E. H. Riague, B. Khater, T. Veszprmi, Organometallics 2007, 26, 2507–2518; c) J.-C. Guillemin, A. Bouayad, D. Vijayku-mar, Chem. Commun. 2000, 1163–1164; d) W. H. H. Gunther, J. Org. Chem. 1966, 31, 1202–1205.
[13] K. Takano, H. Shiraishi, S. Sakaue, (Sumitomo Seika Chemicals Co.), Patent WO 2014050273-A1, 2014. [14] a) L.-C. Song, W. Gao, C. P. Feng, D.-F. Wang, Q.-M.
Hu, Organometallics 2009, 28, 6121–6130; b) D. L. Klay-man, T. S. Griffin, J. Am. Chem. Soc. 1973, 95, 197–199. [15] A. McKillop, D. Koyunc¸u, A. Krief, W. Dumont, P. Renier, M. Trabelsi, Tetrahedron Lett. 1990, 31, 5007– 5010.
[16] L. K. Papernaya, A. A. Shatrova, E. P. Levanova, A. I. Albanov, L. V. Klyba, E. V. Rudyakova, G. G. Levkov-skaya, Heteroat. Chem. 2013, 24, 678–683 and references cited therein.
[17] S. B. Kurbanov, E. S. Mamedov, R. D. Mishiev, N. K. Gusiev, E. A. Agaeva, J. Org. Chem. USSR 1991, 27, 812–816.
[18] a) A. Degl’Innocenti, S. Pollicino, A. Capperucci, Chem. Commun. 2006, 4881–4893; b) A. DeglInnocenti, A. Capperucci, A. Cerreti, S. Pollicino, S. Scapecchi, I. Malesci, G. Castagnoli, Synlett 2005, 3063–3066.
[19] a) A. Capperucci, C. Salles, S. Scarpelli, D. Tanini, Phosphorus Sulfur Silicon Relat. Elem. 2017, 192, 172– 174; b) D. Tanini, A. Capperucci, A. Degl’Innocenti, Eur. J. Org. Chem. 2015, 357–369; c) A. Capperucci, C. Tiberi, S. Pollicino, A. DeglInnocenti, Tetrahedron Lett. 2009, 50, 2808–2810; d) A. Degl’Innocenti, A. Capper-ucci, G. Castagnoli, I. Malesci, C. Tiberi, B. Innocenti, Phosphorus Sulfur Silicon Relat. Elem. 2008, 183, 966– 969.
[20] The use of a catalytic amount of TBAF can be explained on the basis of a proposed mechanism which involves the activation of Het-Si bonds mediated by fluoride ion, as reported also by several authors, even if the real mechanism of the action of TBAF is still not completely clear. For selected examples, see: a) S. Liu, Y. Li, Y. Lan Eur. J. Org. Chem. 2017, 6349–6353; b) V. R. Chintareddy, K. Wadhwa, J. G. Verkade, J. Org. Chem. 2011, 76, 4482–4488; c) ref. [19b] and references cited. According to the suggested mechanism, the activation of HMDSS by TBAF and the subsequent attack on the electrophile leads to hypervalent silicon species (penta- and hexa-coordinated silicon intermedi-ates) and then to the formation of the products after TBAF elimination. The so regenerated fluoride ion can therefore promote the attack of another molecule of the nucleophile.
[21] a) V. R. Mundlapati, D. K. Sahoo, S. Ghosh, U. K. Purame, S. Pandey, R. Acharya, N. Pal, P. Tiwari, H. S. Biswal, J. Phys. Chem. Lett. 2017, 8, 794–800; b) R. Joshi, T. K. Ghanty, T. Mukherjee, S. Naumov, J. Phys. Chem. A 2012, 116, 11965–11972; c) A. J. Mukherjee, S. S. Zade, H. B. Singh, R. B. Sunoj, Chem. Rev. 2010, 110, 4357–4416.
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57
[22] M. J. Frisch, G. W. Trucks, H. B. Schlegel, G. E. Scuseria, M. A. Robb, J. R. Cheeseman, G. Scalmani, V. Barone, B. Mennucci, G. A. Petersson, Gaussian’09 Revision C.01; Gaussian Inc.: Wallingford, CT (USA), 2010. [23] S. F. Boys, F. Bernardi, Mol. Phys. 1970, 19, 553–566. [24] a) P. Wonner, L. Vogel, M. Dser, L. Gomes, F. Kniep,
B. Mallick, D. B. Werz, S. M. Huber, Angew. Chem. Int. Ed. 2017, 56, 12009–12012; b) K. T. Mahmudov, M. N. Kopylovich, M. F. C. Guedes da Silva, A. J. L. Pombeiro
Dalton Trans. 2017, 46, 10121–10138 and references cited therein.
[25] a) K. J. Szabo, H. Frisell, L. Engman, M. Piatek, B. Oleksyn, J. Sliwinski J. Mol. Struct. 1998, 448, 21–28; b) B. M. Goldstein, S. D. Kennedy, W. J. Hennen, J. Am. Chem. Soc. 1990, 112, 8265–8268.
[26] R. N. Salvatore, R. A. Smith, A. K. Nischwitz, T. Gavin, Tetrahedron Lett. 2005, 46, 8931–8935.
