**2. Results and Discussions**

### *2.1. Ti-Mg-Catalyzed Carbozincation of Substituted 1-Alkynylphosphine Sulfides with Et2Zn*

Unfortunately, none of our attempts to perform carbozincation of substituted 1-alkynylphoshine oxides [diphenyl(phenylethynyl)phosphine oxide, hept-1-yn-1-yl(diphenyl)phosphine oxide] with 2.5 equivalents of Et2Zn (1 M in hexane) in the presence of 0.15 equivalent of Ti(O-*i*Pr)4 (0.3 M in hexane) and 0.2 equivalent of EtMgBr (2.5 M in Et2O) in diethyl ether solution at room temperature met with success. However, 1-alkynylphosphine sulfides (hex-1-yn-1-yldiphenylphosphine sulfide, hept-1-yn-1-yldiphenylphosphine sulfide, oct-1-yn-1-yldiphenylphosphine sulfide) proved to be reactive in this reaction. We found that 1-alkynylphosphine sulfides **1** react with 2.5 equivalents of Et2Zn (1 M in hexane) in the presence of 0.2 equivalent of EtMgBr (2.5 M in Et2O) and 0.15 equivalent of Ti(O-*i*Pr)4 (0.3 M in hexane) in diethyl ether at room temperature for 18 h to give, after hydrolysis or deuterolysis, the corresponding substituted *Z*-1-alkenylphosphine sulfides **3a**–**c** and **4a** in high yields (Figure 1).

**Figure 1.** Ti-Mg-catalyzed carbozincation of substituted 1-alkynylphosphine sulfides with Et2Zn in Et2O.

The crucial di fference from the reaction of 1-alkynylphosphines reported in our previous study [1] is that 1-alkynylphosphine sulfides are converted to ethylzincation rather than 2-zincoethylzincation products under the same conditions. In our opinion, the formation of ethylzincation products from alkynylphosphine sulfides proceeds in the following way. According to the presented Figure 2, fast ligand exchange between titanium(IV) isopropoxide and ethylmagnesium bromide yields an unstable diethyltitanium compound, which is then converted to a titanacyclopropane intermediate (titanium(II)–ethylene complex). Generation of a titanacyclopropane complex upon the reaction of Grignard reagents with titanium (IV) alkoxides was first suggested by Kulinkovich [15]. According to Figure 2, the subsequent insertion of 1-alkynylphosphine sulfide into the titanium-carbon bond of titanacyclopropane intermediate **A** results in the formation of titanacyclopentene intermediate **B**. The ligand exchange between intermediate **B** and the Et2Zn molecule yields bimetallic intermediate **C**. The formation of a similar bimetallic complex is postulated in the Zr-catalyzed ethylmagnesiation of inactivated alkenes [16]. The subsequent hydrogen transfer from the ethyl group at the titanium atom of the bimetallic complex C regenerates the titanacyclopropane intermediate and a ffords ethylzincation product **D**.

**Figure 2.** The plausible mechanism of Ti-Mg-catalyzed carbozincation of substituted 1-alkynylphosphine sulfides with Et2Zn.

Unlike reactions of alkyl-substituted alkynylphosphine sulfides, the reaction of (cyclopropylethynyl) diphenylphosphine sulfide is not regioselective and gives a mixture of regioisomers of 1-alkenylphosphines **5** and **6** with *Z*-configuration of the double bond in 1:1 ratio (Figure 3).

**Figure 3.** Ti-Mg-catalyzed carbozincation of substituted (cyclopropylethynyl) diphenylphosphine sulfide with Et2Zn.

The structure of regioisomer **6** with the geminal location of cyclopropyl and ethyl fragments at the double-bond carbon was defined by X-ray diffraction. Presumably, one of the factors responsible for the observed non-selective transformation of cyclopropyl-substituted alkynylphosphine sulfide is the presence of C–C agostic interaction between the titanium atom and cyclopropane ring. The agostic interaction involving cyclopropane moieties was reported for Pt complexes, such as [PtCl2(*c*-C3H6)]2 and PtCl2(*c*-C3H6)(py)2 (py = pyridine) [17], and for lithium cyclopropoxide complex [18,19].

Thus, depending on the substituent, Ti-Mg-catalyzed reaction of functionally substituted alkynes with Et2Zn follows either a 2-zincoethylzincation (1-alkynylphosphines, 2-alkynylamines) [1] or ethylzincation (1-alkynylphosphine sulfides) pathway. In this respect, it was interesting to study the behavior of acetylenic alcohols and ethers in this reaction. Unfortunately, our attempts to perform this reaction with hept-2-yn-1-ol, oct-3-yn-1-ol, or (hept-2-yn-1-yloxy) benzene in diethyl ether failed. Probably, coordination of the titanium ethylene complex (which can be represented as an equivalent of divalent Ti(O-*i*Pr)2 stabilized by ethylene ligand [20]) to the oxygen atom of phosphine oxide, alcohol, or ether group gives a stable unreactive organometallic complex. This complex formation inhibits titanium coordination to the triple carbon–carbon bond and thus prevents the formation of titanacyclopentene.

### *2.2. The EtMgBr and Ti(O-iPr)4-Catalyzed 2-Zincoethylzincation of Substituted Substituted Propargylamines with Et2Zn*

In view of the presumed importance of various ligand coordination effects for this reaction, we studied the EtMgBr and Ti(O-*i*Pr)4-catalyzed reaction of substituted propargylamines with Et2Zn in solvents of different nature. The reaction of *<sup>N</sup>*,*<sup>N</sup>*-dimethylbut-2-ynyl-1-amine **7a** with 2.5 equivalents of Et2Zn (1 M in hexane) in the presence of 0.15 equivalent of Ti(O-*i*Pr)4 (0.3 M in hexane) and 0.2 equivalent of EtMgBr (2.5 M in Et2O) was equally efficient in diethyl ether, anisole, dichloromethane, hexane, benzene, or toluene and resulted in regio- and stereoselective formation of dideuterated allylamine **8a** with *Z*-configuration (Figure 4). Similar results were obtained for *<sup>N</sup>*,*<sup>N</sup>*-dimethylundec-2-ynyl-1-amine, 1-(hept-2-yn-1-yl)piperidine, *<sup>N</sup>*,*<sup>N</sup>*-dimethylnon-2-ynyl-1-amine, and 4-(hept-2-yn-1-yl)morpholine. More evidence for the structure of the resulting allylamines was gained by converting them to iodinolysis products **10c** and **10e**. Meanwhile, *<sup>N</sup>*,*<sup>N</sup>*-dimethylbut-2-ynyl-1-amine **7a** proved to be completely inert towards the reaction carried out in 1,4-dioxane, tetrahydrofuran, 1,2-dichloroethane, 1,2-dimethoxyethane, chloroform, or triethylamine.

**Figure 4.** EtMgBr and Ti(O-*i*Pr)4-catalyzed 2-zincoethylzincation of substituted propargylamines with diethylzinc in various solvents.

We suggested that in the case of 1,2-dimethoxyethane, 1,4-dioxane, tetrahydrofuran, and triethylamine, the acetylenic substrate molecule cannot displace the solvent molecule from the coordination sphere of the low-valence titanium atom in intermediate **E** (Figure 5) and, hence, intermediate **F** is not formed and the catalytic cycle is interrupted. Quantum chemical B3LYP/6-31G(d,p) modeling of the step of displacement of a solvent molecule by *<sup>N</sup>*,*<sup>N</sup>*-dimethylbut-2-ynyl-1-amine, which was chosen as the model compound, demonstrated that the ease of displacement (Gibbs free energy) increases in the series Et3N (−3.1 kcal/mol) < THF (−4.9 kcal/mol) < Me2O (−6.5 kcal/mol). According to quantum chemical calculations, for dichloromethane, hexane, or aromatic hydrocarbons (benzene, toluene) as solvents, the equilibrium between intermediates **A** and **E** is shifted towards the non-solvated titanacyclopropane **A**, which facilitates the formation of intermediate **F**.

**Figure 5.** Ligand exchange in the coordination sphere of the titanium atom of titanacyclopropane intermediate.

Despite similar natures of dichloromethane, 1,2-dichloroethane, and chloroform, the reaction smoothly proceeds in dichloromethane, but does not take place in 1,2-dichloroethane or chloroform. In our opinion, this difference may be attributable to the instability of chloroform and 1,2-dichloroethane under conditions of reaction with EtMgBr and Ti(O-*i*Pr)4. The use of these solvents in organomagnesium chemistry is fairly limited. For instance, it is known that phenylmagnesium bromide and ethymagnesium iodide readily react with chloroform and tetrachloromethane to give dihalocarbenes [21]. On the other hand, there are many examples of cross-coupling reactions of Grignard reagents with polychlorinated solvents activated by transition metal catalysts [22–26].

### *2.3. EtMgBr and Ti(O-iPr)4-Catalyzed 2-Zincoethylzincation of Substituted 1-Alkynylphosphines with Diethylzinc*

In connection with the obtained results, we were interested in studying the effect of various solvents on the EtMgBr and Ti(O-*i*Pr)4-catalyzed reaction of *P*-containing alkynes—1-alkynylphosphines, 1-alkynylphosphine sulfides, and 1-alkynylphosphine oxides with Et2Zn. The reaction of substituted 1-alkynylphosphines **11** with 2.5 equivalents Et2Zn (1 M in hexanes) in the presence of 0.15 equivalent Ti(O-*i*Pr)4 (0.3 M in hexanes) and 0.2 equivalent EtMgBr (2.5 M in Et2O) at room temperature followed by oxidation with an aqueous solution of H2O2 (37%) or sulfuration with elemental sulfur is equally effective in diethyl ether [1], methylene chloride, hexane, and toluene with regio- and stereoselective formation of the corresponding 1-alkenylphosphine oxides and sulfides of the *Z*-configuration **12a**, **13b**,**<sup>c</sup>** and **14c** (Figure 6).

**Figure 6.** Ti-Mg-catalyzed carbozincation of substituted 1-alkynylphosphines with Et2Zn in various solvents.

It should be noted that for the complete conversion of 1-alkynylphosphines **11** at room temperature in methylene chloride, toluene, and hexane, about 48 h are required. An increase in temperature to 40 ◦C leads to a deterioration in the selectivity of the reaction and the formation of difficult-to-analyzemixture of products. As expected, hept-1-yn-1-yldiphenylphosphine oxide was inert not only in diethyl ether (as described above) but also in methylene chloride, toluene, and hexane. At the same time, the Ti-Mg-catalyzed reaction of substituted 1-alkynylphosphine sulfides with Et2Zn in methylene chloride, toluene, and hexane does not proceed stereoselectively and leads to the formation of a mixture of stereoisomers. For example, the reaction of hept-1-yn-1-yldiphenylphosphine sulfide **15** with 2.5 equiv. Et2Zn (1 M in hexanes) in the presence of 15 mol. % Ti (O-*i*Pr)4 (0.3 M in hexanes) and 20 mol. % EtMgBr (2.5 M in Et2O) in methylene chloride leads to the formation of a mixture of **16** (*Z*)- and **17** (*E*)-isomers in a 2:1 ratio with a total yield of 71% (Figure 7).

**Figure 7.** Ti-Mg-catalyzed carbozincation of substituted hept-1-yn-1-yldiphenylphosphine sulfide.

The formation of an isomeric mixture is indicated in the 13C NMR spectrum of the reaction products by the presence of a double set of signals in a 2:1 ratio of the following carbon atoms: C-6 (δ 168.3 ppm and δ 168.1 ppm), C-7 (δ 31.2 ppm and δ 27.1 ppm), C-8 (δ 12.2 ppm and δ 11.5 ppm), C-9 (δ 34.2 ppm and δ 37.9 ppm), C-10 (δ 27.1 ppm and δ 27.5 ppm), C-11 (δ 31.9 ppm and δ 31.6 ppm)), C-12 (δ 22.4 ppm and δ 22.5 ppm), C-13 (δ 13.9 ppm and δ 14.1 ppm). The Overhauser effects observed in the NOESY spectrum between the methylene group H2C-9 (δ 2.39 ppm) and the protons of the aromatic substituent of the compound **16**, as well as the cross-interaction between the protons H2C-7 (δ 2.27 ppm) and HC-5 (δ 6.03 ppm) of the compound **17** allowed us to identify the obtained adducts as *Z*- and *E*-isomers, respectively.
