Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

3-Methylbuta-1,2-dien-1-ylphosphonic acid derivatives (phosphorylallenes) [X2(O=)P–CR=C=CMe2, X = Cl, OMe, NR2, or SAr] undergo intramolecular cyclization into the corresponding 1,2-oxaphospholium ions in the Brønsted superacid TfOH. These cations have been thoroughly studied by means of NMR spectroscopy. The hydrolysis of superacidic solutions of these species afforded cyclic phosphonic acids and other phosphorus-containing compounds. Contrary to Brønsted acids, 3-methylbuta-1,2-dien-1-ylphosphonic dichloride [Cl2(O=)P–HC=C=CMe2] reacted with the Lewis acid AlCl3 in an intermolecular way forming noncyclic intermediates, which were investigated by NMR spectroscopy and DFT calculations. Hydrolysis of these species resulted in the formation of phosphoryl-substituted allyl alcohols and 1,3-butadienes. A strong coordination of the oxygen of the P=O group with AlCl3 prevented the formation of cyclic 1,2-oxaphospholium ions and played a crucial role in the different reactivity of such phosphorylallenes under the action of Brønsted or Lewis acids. Apart from that, the reaction of dichlorophosphorylallenes with arenes and AlCl3 led to products of hydroarylation of the allene system, phosphoryl-substituted alkenes and/or indanes. This is the first example of a Lewis acid-promoted intermolecular hydroarylation of allenes bearing electron-withdrawing substituents. Plausible reaction mechanisms have been proposed on the basis of the investigated reactions, and NMR analysis and DFT studies of the intermediate cationic species.


Abstract
3-Methylbuta-1,2-dien-1-ylphosphonic acid derivatives (phosphorylallenes) [X 2 (O=)P-CR=C=CMe 2 , X = Cl, OMe, NR 2 , or SAr] undergo intramolecular cyclization into the corresponding 1,2-oxaphospholium ions in the Brønsted superacid TfOH. These cations have been thoroughly studied by means of NMR spectroscopy. The hydrolysis of superacidic solutions of these species afforded cyclic phosphonic acids and other phosphorus-containing compounds. Contrary to Brønsted acids, 3-methylbuta-1,2-dien-1-ylphosphonic dichloride [Cl 2 (O=)P-HC=C=CMe 2 ] reacted with the Lewis acid AlCl 3 in an intermolecular way forming noncyclic intermediates, which were investigated by NMR spectroscopy and DFT calculations. Hydrolysis of these species resulted in the formation of phosphoryl-substituted allyl alcohols and 1,3-butadienes. A strong coordination of the oxygen of the P=O group with AlCl 3 prevented the formation of cyclic 1,2-oxaphospholium ions and played a crucial role in the different reactivity of such phosphorylallenes under the action of Brønsted or Lewis acids. Apart from that, the reaction of dichlorophosphorylallenes with arenes and AlCl 3 led to products of hydroarylation of the allene system, phosphoryl-substituted alkenes and/or indanes. This is the first example of a Lewis acid-promoted intermolecular hydroarylation of allenes bearing electron-withdrawing substituents. Plausible reaction mechanisms have been proposed on the basis of the investigated reactions, and NMR analysis and DFT studies of the intermediate cationic species.
It should be especially emphasized that intermolecular reactions of phosphorylallenes with arenes have not been yet achieved. In general, intermolecular hydroarylation of allenes has been developed for reactions catalyzed by complexes of various metals [17], such as Pd [18][19][20], Pt [21], Au [22][23][24][25], Ir [26], Rh [27,28], and Co [29]. However, only electron-rich allenes, bearing electron-donating substituents, take part in the metal-catalyzed reactions. There are just a few examples of Brønsted acid catalyzed intermolecular hydroarylations of allenes by electron-rich arenes, indoles [30] or phenols [31]. Other arenes (benzene and its substituted derivatives) have not been involved in these reactions. Concerning electron-deficient allenes, bearing electron-withdrawing groups, there is only one example of a trifluoroacetic acid-promoted hydroarylation with indoles [30]. To the best of our knowledge, up to the moment, there are no examples for an intermolecular hydroarylation of electron-deficient allenes by benzene derivatives under the action of strong Brønsted or Lewis acids.
The main goals of this work were to study transformations of various phosphorylallenes under electrophilic activation with Brønsted or Lewis (super)acids, including reactions with arenes as π-nucleophiles, and investigation of intermediate cationic species by means of NMR and DFT calculations.

Reactions of allenes with Brønsted acids
Allenes 1a,b,e-j upon dissolving in TfOH in an NMR tube at room temperature formed intensively colored solutions of the corresponding 1,2-oxaphospholium ions A-H (Table 1). These species are formed by protonation of the central carbon atom of the allene system that gives the corresponding allyl cations, which undergo cyclization onto the oxygen of the P=O group. These ions have similar NMR data: the signal of the new proton H4 is located in the range 6.30-8.07 ppm, the signal of vinyl carbon C4 at 166.8-171.9 ppm, and the signal of quaternary carbon C5 at 96.0-116.3 ppm. It is worth noting that 2,2dichloro (A, B) and 2,2-diarylsulfanyl (F, G)-substituted cations exhibit down field shifted signals in the 31 P NMR (δ 87.82-115.37 ppm) in comparison with 2,2-diamino (C, D, E1) and 2,2-dimethoxy (H)-substituted species (δ 31 P 52.87-70.79 ppm). This reveals that, for amino and methoxy substituents, positive charge is delocalized onto these groups to a greater extent than in the case of chloro or arylsulfanyl ones. Cations A-D, and F-H are stable in TfOH at room temperature for a long time, they are not transformed into other species under the superacidic conditions. Unlike the others, allene 1g undergoes consequent transformations in TfOH at room temperature (see Scheme 1 and Figure 2). First, when dissolved in the acid, allene 1g forms oxaphospholium ion E1 (Table 1) through an intermediate formation of allyl cation E (Scheme 1). Ion E1 is transformed very fast into another species; after one minute new signals appear in the NMR spectra (see 31 P NMR monitoring of this process in Figure 2), and after 12 hours it is completely converted to this new cation. It is most likely that this species is 1,2-azaphosphol-2-ium ion E2, which is formed through allyl cation E.
However, cation E2, in turn, is further transformed into one more species during several days. The set of spectral data (see below) for this final species indicates that, most likely it should be seven-membered heterocyclic cation E4, which is formed through the P-N bond cleavage in E2 and formation of intermediate cation E3 (Scheme 1).
In the 31 P NMR spectra, the signal of E4 is the most up field shifted (δ 24 ppm, see Figure 2 and Scheme 1) in comparison with signals of the species E1 (δ 53 ppm) and E2 (δ 43 ppm). This difference may reveal that phosphorus in cation E4 is bound to a carbon atom, rather than to a heteroatom O or N, like in E1 and E2. Structurally close six-membered ring cations, having the C-P bond, resonate at 30.5-31.9 in 31 P NMR [16], that is close to the spectrum for species E4.
Apart from that, in 13 C NMR spectra, the signals of quaternary carbon bearing two methyl groups in E2 and E4 are very close (δ 70.3-70.9 ppm, see Scheme 1). Contrary to that, the signal of this carbon for E2 is very much down field shifted (δ 96.1 ppm). This indicates that in species E2 and E4 this carbon is connected to a protonated amino group, and in E1 it is bound to oxygen. The same range of absorbance around 100 ppm for this carbon was observed previously for other oxaphospholium ions [14,16].
Then, we carried out hydrolysis of cations A-H (Scheme 2).
Results of hydrolysis strongly depend on the substituent X on the phosphorus atom. Ions containing a labile P-X bond (X = Cl, O, S), namely A, B, and F-H, gave unstable adducts 2 (registered by GC-MS), which are further transformed into acids 3. The structure of compound 3a was confirmed by X-ray  F-H with morpholine (Scheme 3). Amides 6a,b were isolated as products of these reactions in excellent yields. The plausible reaction mechanism includes at the first stage nucleophilic attack of morpholine onto the phosphorus cationic center that gives cation I, which is transformed into species J. Hydrolysis of the latter leads to cation K and then finally to amides 6a,b.

Scheme 3: Preparation of amides 6a,b from cations A, B, and F-H.
We carried out a large-scale one-pot solvent-free synthesis of amides 6a,b starting from propargyl alcohols 7a,b at room temperature (Scheme 4). At the first step, alcohols 7a,b in the reaction with PCl 3 were transformed into the corresponding allenes 1a,h. Then, the addition of Brønsted acid (TfOH or H 2 SO 4 ) gave cations A and B, respectively. The interaction of these species with morpholine followed by hydrolysis furnished the target amides 6a,b in total yields of 60-90% (see procedures in Supporting Information File 1).
It should be noted that allene 1d bearing no alkyl groups and monoalkylated allene 1c formed complex mixtures of oligomeric products under the action of various Brønsted acids (H 2 SO 4 , FSO 3 H, TfOH). In this case, the intermediate oxaphospholium ions are unstable and undergo consequent transformations. Apart from that, attempts to quench cations A-H with external aromatic π-nucleophiles failed. No products of intermolecular electrophilic aromatic substitution were obtained.

Reactions of allenes with Lewis acid AlCl 3
Then, we checked reactions of allenes 1a-j with and without benzene under the action of the strong Lewis acid AlCl 3 , using benzene or dichloromethane as a solvent, followed by hydroly- sis of the reaction mixtures. Allenes 1c-j gave complex mixtures of oligomeric products under these conditions. However, allenes 1a,b afforded the desired product of hydroarylation with benzene (vide infra).
AlCl 3 -promoted reactions of allene 1a were studied under various conditions (Table 2). This compound in reaction with AlCl 3 without benzene afforded a mixture of allyl alcohol Z-9 and diene E-10a after aqueous work-up ( Table 2, entries 1 and 2). The amount of 2.1 equivalents of AlCl 3 is sufficient for activation of this transformation (compared to the amount of AlCl 3 in entries 1 and 2, Table 2). On the other hand, 1 equivalent of AlCl 3 is not enough to activate allene 1a; thus, under these conditions, only acid 2 was obtained as a product of the hydrolysis of starting compound 1a ( Having these conditions for hydroarylation of allene 1a in hand ( Table 2, entry 4), we conducted reactions with the series of arenes (Table 3). An excess of methanol was used for quenching of reaction mixtures instead of water. This treatment produced dimethoxyphosphoryl groups [(MeO) 2 P=O] in the reaction products, rather than the acidic group [(HO) 2 P=O] in compounds 8-11a ( Table 2). The presence of the (MeO) 2 P=O group in the structures of reaction products makes them more soluble in organic solvents and easy to isolate in preparative reactions.
It should be emphasized that compounds 11 and 12 were obtained as inseparable mixtures after TLC separation due to their close chromatographic retention parameters. However, E-and Z-isomers of alkenes 11 can be separated by preparative thin-layer chromatography, for instance, compounds E-11m and Z-11m (Table 3, entry 9 and Supporting Information File 1).
The E/Z-stereochemistry of compounds 11 was determined on the basis of the values of spin-spin interaction constants of vinyl protons, which were 13-14 Hz for Z-isomers and 17-18 Hz for E-isomers (see Supporting Information File 1).
In the same reaction with benzene, allene 1b afforded alkene Z-11n in high yield (Scheme 5). The use of morpholine for quenching of the superacidic reaction mixture gave amide Z-11o in the reaction of 1a with benzene (Scheme 6).

Scheme 6:
Reaction of allene 1a with benzene under the action of AlCl 3 followed by quenching of the reaction mixture with morpholine leading to amide Z-11o.
We also conducted a large-scale one-pot synthesis of indane 12d starting from 2-methylbut-3-yn-2-ol (Scheme 7, see procedure in Supporting Information File 1). The first stage of this procedure gave allene 1a, which was dissolved in CH 2 Cl 2 and subjected to reaction with p-xylene under the action of AlCl 3 . Finally, methanolysis of the reaction mixture resulted in the formation of indane 12d in a total yield of 78%.
To elucidate the reaction mechanism additional experiments were conducted. First of all, alkenes 11 were subjected to the action of five-fold excess of AlCl 3 at room temperature or elevated temperature. However, no formation of indanes 12 was detected. Then we carried out an NMR study to catch the reaction intermediates. Upon mixing of allene 1a with 1 equivalent of AlCl 3 in CD 2 Cl 2 in an NMR tube at room temperature, a yellow solution was formed, which was most likely a complex of 1a with AlCl 3 , which is coordinated onto oxygen of the P=O group. The comparison of 1 H, 13 C, and 31 P NMR spectra of starting 1a and its complex with AlCl 3 13 is presented in Figure 3 (see full spectral data in Supporting Information File 1). It is clear that the complex formation led to significant broadening of NMR spectral lines and, mainly, a downfield shift of the corresponding signals, due to large positive charge on the phosphorus atom. This solution was stable for a long time (several days) and complex 13 was not converted into other compounds. It must be reminded here, that allene 1a did not react with benzene under the action of 1 equivalent of AlCl 3 (see Table 2, entry 3).
Addition of more than 1 equivalent of AlCl 3 (2-5 equivalents) to a solution of 1a in CD 2 Cl 2 in an NMR tube resulted in an immediate formation of diene E-14 as a part of a complex mixture (Scheme 8, see Supporting Information File 1 for NMR). Compare with the same transformations of 1a followed by hydrolysis of the reaction mixture affording a mixture of alcohol Z-9 and diene E-10a ( Table 2, entries 1 and 2). The formation of compound 14 in an NMR monitoring experiment may also indicate that alcohol Z-9 is formed upon hydrolysis of allene 8 ( Table 2, entries 1 and 2). Reaction of allene 1a with deuterobenzene C 6 D 6 (1 equivalent) under the action of AlCl 3 (2 equivalents) in CD 2 Cl 2 in an NMR tube gave alkene 15 (Scheme 8) analogously to the formation of alkenes 11 (Table 3).
Thus, the different reactivity of these particular dichlorophosphorylallenes under the action of Brønsted or Lewis acids can be explained by involvement of the P=O group in intra-or intermolecular interactions at the formation of cationic intermediates. Strong coordination of Lewis acid AlCl 3 with the P=O group completely deactivates it for further intramolecular reac- tions ( Figure 3, Table 2). Despite solvation in the Brønsted superacid TfOH, the P=O group takes part in intramolecular cyclization into oxaphospholium ions (Table 1). These two dif-ferent types of reaction intermediates, generated from such allenes in Brønsted and Lewis acids, lead to various reaction products. In accordance with both mechanisms A and B, yields of indanes 12 should be increased for substrates having electron-donating groups, Ar. Indeed, the highest yields of indanes 12 were achieved for the reactions of allene 1a with the electron-rich arenes toluene and xylenes (Table 3, entries 2-5).

Conclusion
Transformations of various phosphorylallenes under the action of strong Brønsted or Lewis acids were studied. These allenes showed different reactivity depending on the type of the acid. In the Brønsted superacid TfOH, the allenes were transformed into oxophospholium cations. Hydrolysis (or morpholinolysis) of these species afforded a series of phosphorous-containing compounds, cyclic phosphoric acids and their derivatives, and other substances. Contrarily, reactions of dichlorophosphorylallenes with the Lewis acid AlCl 3 proceeded through the formation of non-cyclic intermediates. Hydrolysis of the latter afforded phosphorylallyl alcohols and butadienes. For the first time, the intermolecular hydroarylation of the allene system of dichlorophosphorylallenes by arenes under the action of AlCl 3 was achieved. This reaction gave rise to phosphoryl-substituted alkenes and indanes. The intermediates of these reactions were investigated by means of NMR and DFT calculations, that shed light on the reaction mechanisms.

Supporting Information
Supporting Information File 1 Experimental part.