CC BY-ND-NC 4.0 · SynOpen 2019; 03(01): 4-10
DOI: 10.1055/s-0037-1611666
paper
Copyright with the author

Highly Regio- and Stereoselective Hydrogermylation of Fluorinated Alkyl Propiolate

Ranin. Kawtharani
a  Laboratoire de Physico-Chimie des Matériaux et des Electrolytes pour l’Energie (PCM2E). EA 6299, Avenue Monge Faculté des Sciences, Parc de Grandmont, 37200 Tours, France   Email: mohamed.abarbri@univ-tours.fr
b  Laboratoire de Chimie Médicinale et de Produit naturels, Université Libanaise, Faculté des Sciences I, Hadat, Lebanon
,
Mirvat Elmasri
b  Laboratoire de Chimie Médicinale et de Produit naturels, Université Libanaise, Faculté des Sciences I, Hadat, Lebanon
,
Khalil Cherry
c  Laboratoire Matériaux, Catalyse, Environnement et Méthodes Analytiques (MCEMA), Campus Universitaire de Hadat, Université Libanaise, Lebanon
,
Johan Jacquemin
a  Laboratoire de Physico-Chimie des Matériaux et des Electrolytes pour l’Energie (PCM2E). EA 6299, Avenue Monge Faculté des Sciences, Parc de Grandmont, 37200 Tours, France   Email: mohamed.abarbri@univ-tours.fr
,
Mohamed Abarbri*
a  Laboratoire de Physico-Chimie des Matériaux et des Electrolytes pour l’Energie (PCM2E). EA 6299, Avenue Monge Faculté des Sciences, Parc de Grandmont, 37200 Tours, France   Email: mohamed.abarbri@univ-tours.fr
› Author Affiliations
Further Information

Publication History

Received: 03 December 2018

Accepted: 04 January 2019

Publication Date:
28 January 2019 (online)

 

Abstract

The selective introduction of fluoroalkylated vinylmetals in controlled strategies is a challenging process for many chemists. This study reports the highly regio- and stereoselective synthesis of functionalized vinylgermanes bearing a perfluoroalkyl group from per­fluoroalkylated acetylenic esters via AlCl3-catalyzed hydrogermylation. Regio- and stereoselectivity are highly dependent on the nature of the catalyst and the nature of the fluoroalkyl group of alkyne.


#

The field of organofluorine chemistry plays an important role in various applications including agrochemicals, soft materials, and especially pharmaceuticals, for which they are widely used as anticancer, antiarrhythmic, anti­hypertensive agents, anti-inflammatory, antidepressant, and antibiotics.[1] [2] [3] In fact, the unique properties of fluorine has an exceptional impact on the electronic, lipophilic, and steric parameters, and on the acidity or basicity of organofluorinated molecules. Accordingly, the incorporation of fluorine atoms and perfluoroalkyl groups into organic compounds can modify their physiochemical properties, improve their metabolic stability, and change their biological activities.[4] Therefore, the introduction of fluorinated building blocks in controlled strategies is considered an ­interesting challenge for many researchers, particularly those studying fluoroalkylated vinyl metals.[5] [6] However, the selective introduction of (E) and (Z) fluoroalkylated alkenes in the structure of natural products is still daunting.

There are a few synthetic strategies that enable such an operation including the direct sp2 C–H bond functionalization,[7] and olefination reactions.[8] However, these methods suffer from limitations and stereoselectivity issues. Provided that regio- and stereoselectivity of the hydrometallation could be controlled, an efficient approach that would afford a straightforward entry to the selective preparation of low toxic fluoro-polysubstituted alkenes would rely on the ­hydrogermylation/cross coupling sequences from alkynes bearing fluorinated moieties. Although, germanium is slightly more expensive than tin, it is closer to silicon in its organic chemistry. Furthermore, germanium has a higher thermal stability,[9] and a lower toxicity than tin.[10]

The addition of organogermanes to alkynes is the best method for the direct synthesis of vinylgermanes.[11] [12] However, hydrogermylation of carbonyl functionalized fluorinated alkynes, which provides a new entry to a wide range of functional fluorinated compounds, is still under investigation. To our knowledge, no hydrogermylation reaction of fluorinated alkynes type 1a [13] has been described in the open literature. It is worth mentioning that we recently reported the first highly regio- and stereoselective free-metal hydrostannylation of ethyl 4,4,4-trifluorobut-2-ynoate (1a) leading to the synthesis of α and β-tributylstannyl-4,4,4-trifluorobut-2-enoates without any additives (Scheme [1]).[14]

Zoom Image
Scheme 1 Previously described hydrostannylation of ethyl 4,4,4-tri­fluorobutenoate (1a)

As a continuation of our previous study on the hydrometalation reaction of fluorinated alkynes for the preparation of new vinylmetals bearing a perfluoroalkyl group,[14] [15] we report herein, for the first time, a highly regio- and stereo­selective hydrogermylation reaction of fluorinated alkynes of type 1 using the inexpensive Lewis acid AlCl3 as catalyst.

We first sought to determine the best conditions for a highly regio- and stereoselective hydrogermylation reaction of fluorinated ethyl propiolate 1a with Ph3GeH using different solvents and additives. The results are summarized in Table [1].

First, we examined the free-metal hydrogermylation of 1a using triphenylgermanium hydride in different solvents. Importantly, and contrary to what is generally observed in the case of hydrostannylation of alkyne 1a,[14] the regioselectivity of this hydrogermylation reaction is relatively independent of the nature of the solvent (Table [1], entries 1–3). Thus, using hexane, methanol or dichloromethane as solvent, the hydrogermylation of alkyne 1a leads to the formation of the four possible isomers (Z)-, (E)-, (Z)- and (E)-. In all cases, the regioselectivity is greatly in favor of the β-regioisomer (>75 %). Although the ratio of formation of both α- and β-adducts is not exactly the same in each selected solvent, it is clear that the polarity of the solvents does not have a significant impact on the hydrogermylation reaction.

The regiochemistry of vinylgermanes was then deduced without ambiguity from NMR data, especially from the J H–F coupling patterns (Figure [1]). Indeed, in the case of the α-regio­isomer, the coupling constant 3 J H–F reaches a value of ca. 7–8 Hz, whereas in the case of the β-regioisomer the coupling constant 4 J H–F is close to 1–2 Hz. These values are consistent with previously published work.[16]

Zoom Image
Figure 1 3 J H–F and 4 J H–F coupling constants of the two regioisomers α and β, respectively

For further investigations, the hydrogermylation of alkyne 1a was carried out under similar conditions in the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) as a radical scavenger (Table [1], entry 4). Remarkably, the β-regioisomer was not formed and only the α-isomer was isolated in 21% yield as a 64:36 mixture of the geometric isomers (E)- and (Z)-, respectively. These results suggest that the reaction mechanism leading to the formation of the β-regioisomer takes place according to a radical process, while the α-isomer could be the product of an ionic pathway. Furthermore, these results indicate that the free-metal hydrogermylation reaction proceeds mainly by a free radical mechanism. Organogermanium hydrides have been used for the radical and transition-metal-catalyzed hydrogermylation of alkynes since the mid-1950s, but such transformations still suffer from serious limitations such as low regio- and stereoselectivities.[17] [18] [19] However, Blanchard et al. developed two efficient stereocomplementary routes for nonfunctionalized (Z)- and (E)-α-trifluoromethylvinylgermanes by regio- and stereoselective hydrogermylation of α-trifluoromethylated alkynes under transition-metal-catalyzed conditions or in presence of a radical initiator.[20] Inspired by these results, fluorinated alkyne 1a was treated in dichloromethane with 1 equivalent of Ph3GeH in the presence of a catalytic amount of Pd(PPh3)4 (5 mol %). The 1H and 19F NMR spectra of the crude hydrogermylation product reveal a 60:40 mixture of the α and β regioisomers was formed, respectively (entry 5). The (E)- adduct, resulting from a cis-addition, constitutes the major product.

To explore more synthetic routes to perform the highly regio- and stereoselective hydrogermylation of alkyne 1a, we next directed our attention to the radical hydrogermylation of alkyne 1a. The treatment of alkyne 1a with Ph3GeH at room temperature using ammonium persulfate,[21] as ­radical initiator in aqueous acetonitrile, provides a mixture of the α- and β-regioisomers in a ratio of about 22:78, with a majority of the trans-addition product (Z)- (Table [1], ­entry 6). Similar results were obtained but with a lower yield when we used the known radical initiator triethylborane BEt3 [22] (entries 7). Another class of catalyzed hydrogermylation reaction of functionalized alkynes was reported in 2005 based on the use of an expensive Lewis acid such as B(C6F5)3.[23] Gevorgyan et al. demonstrated that the stereochemistry of this hydrogermylation reaction depends on the nature of the alkyne used; the reaction proceeded via a trans-addition pathway with simple alkynes and cis-addition with ethyl propiolate. Applying the same conditions as Gevorgyan et al., by using BPh3, a less expensive Lewis acid than B(C6F5)3, the hydrogermylation of alkyne 1a with Ph3GeH proceeds mainly by trans-addition, yielding the major product (Z)- with a small amount of the α-adduct (entry 8).

Lewis acid AlCl3 mediated hydrosilylation and hydro­stannylation of alkynes have been reported,[24] but AlCl3 has never been used in the case of the hydrogermylation of alkynes. We therefore decided to perform the hydrogermylation reaction of alkyne 1a at room temperature in the presence of a catalytic amount of AlCl3 (10 mol%) in toluene during 2 h. Remarkably, complete α-regioselectivity of the hydrogermylation of alkyne 1a was observed, yielding α-triphenylgermylacrylate as the sole regioisomer in 74% yield (Table [1], entry 9). Furthermore, the stereoselectivity was also greatly in favor of the (E)-isomer (E > 93%). Surprisingly, complete regio- and stereoselectivity of the hydro­germylation reaction was observed in the presence of a catalytic amount of AlCl3 (10 mol%) using CH2Cl2 as solvent, yielding (E)- as the sole product with excellent yield (entry 10).

In view of these results, we deduced that the optimum conditions for the hydrogermylation reaction of alkyne 1a to produce the corresponding trans-vinylgermane (E)- in a complete regio- and cis-stereoselective manner is 1 mol of Ph3GeH and 10 mol% of AlCl3 in CH2Cl2 at room temperature for 2 h.

Table 1 Hydrogermylation Reaction Conditions for 1a

Entry

Solvent

Additive (%)

α/β

(Z)- (%)

(E)- (%)

(Z)- (%)

(E)- (%)

Yield (%)

1

methanol

24:76

14.0

9.8

68.9

6.3

39a

2

hexane

24:76

13.2

10.4

68.3

7.8

35a

3

CH2Cl2

20:80

14.8

5.5

78.1

1.6

65a

4

CH2Cl2

TEMPO

100:0

36.0

64.0

0.0

0.0

21b

5

CH2Cl2

Pd(PPh3)4 (5)

60:40

0.7

59.5

29.7

10.1

31a

6

CH3CN/H2O

(NH4)2S2O8 (20)

22:78

18.4

3.9

76.9

0.8

83a

7

CH2Cl2

Et3B (10)

32:68

25.6

7.0

63.5

4.1

50a

8

CH2Cl2

BPh3 (10)

26:74

17.0

9.0

74.0

0.0

77a

9

toluene

AlCl3 (10)

100:0

6.6

93.4

0.0

0.0

74b

10

CH2Cl2

AlCl3 (10)

100:0

0.0

100.0

0.0

0.0

92b

a Evaluated by 1H NMR and 19F NMR.

b Yield of isolated product.

The E- and Z-configurations of the two regioisomers and were assigned based on the values of the coupling constant [3 J(C(2)-F)]; for which 3 J[C(2)-F] of the (Z)-isomer is higher than that of the (E)-isomer (Figure [2]).[16] [20]

Zoom Image
Figure 2 E- and Z- configuration assignments of the two regioisomers α and β

To investigate the scope and limitations of the AlCl3-­catalyzed hydrogermylation reaction, we next tested the hydrogermylation reaction of alkyne 1a using a less hindered organogermane compound such as Bu3GeH. Remarkably, complete α-regioselectivity of the hydrogermylation of alkyne 1a was observed. However, the reaction was found to be highly but not completely stereoselective, because traces of the Z-stereoisomer were observed (E/Z = 91:9). Therefore, it seems that the size of the R group on R3GeH is at the origin of this result. To further investigate the regiochemistry of vinylgermane 3, we then tested the radical hydrogermylation of alkyne 1a using Bu3GeH in the presence of Et3B as a radical initiator and CH2Cl2 as solvent, providing a mixture of the four possible isomers (Z)-, (E)-, (Z)- and (E)- with the majority being the trans-addition product (Z)- (Scheme [2]).

Zoom Image
Scheme 2 Hydrogermylation reactions of 1a using Bu3GeH

Another fluorinated α,β-acetylenic ester, ethyl 4,4,5,5,5-pentafluoropent-2-ynoate (1b),[13] was then treated under the same conditions as those described above. The results obtained were very similar to those obtained in the case of alkyne 1a. The hydrogermylation of alkyne 1b using AlCl3 as catalyst in CH2Cl2 and Ph3GeH yields exclusively the cis-addition product (E)- in 91% yield. Likewise, as observed in the case of alkyne 1a, there was a slight loss of stereo­selectivity when triphenylgermane was substituted with the less bulky tributylgermane, but the regioselectivity remained complete. Similarly, radical hydrogermylation of alkyne 1b using Bu3GeH or Ph3GeH in the presence of Et3B was performed, yielding a mixture of α- and β-regioisomers in a ratio of ca. 33:67, respectively, with the majority of the trans-addition product (Z)- and (Z)- (Scheme [3]).

Zoom Image
Scheme 3 Hydrogermylation of 1b using Ph3GeH and Bu3GeH

To better understand the role of the fluorinated group of the alkyne in the orientation of the regioselectivity of the AlCl3-catalyzed hydrogermylation reaction, hydrogermylation of methyl 4,4-difluoro-4-phenylbut-2-ynoate (1c)[25] using Ph3GeH was performed under the conditions described above (Scheme [4]). Although the reaction gave the (E)- adduct as the major isomer, it was accompanied by the formation of the other three isomers in the proportions: (Z)- (7%), (E)- (55%), (Z)- (34%) and (E)- (4%).

Zoom Image
Scheme 4 AlCl3-catalyzed hydrogermylation of 1c using Ph3GeH

It is worth mentioning that the regio- and stereochemistry for the vinylgermanes 3, 4, 5 and 6 were deduced from the 3 J H–F, 4 J H–F and 3 J C–F coupling patterns by following the analyses described above in case of vinylgermane 2.

Despite the limited number of fluorinated alkynes used, it seems that the regioselectivity of this hydrogermylation reaction is also very dependent on the nature of the fluorinated group of the alkyne. This dependence may be related to the difference of the partial charges on sp-carbon atoms of the alkyne. To investigate this in greater detail, ab initio calculations were carried out (full minimization of the structure realized using the HF/6-311G* level of theory followed by a single-point calculation with the basic set DFT/B3-LYP/def-TZVP within Turbomole 7.2) to determine the partial charge of these two sp-carbon atoms (Scheme [5]), thanks to the Natural Population Analysis approach.[26] A larger difference on the partial charges (Δ = δC3–δC2) was observed in the cases of alkynes 1a and 1b than in alkyne 1c (Figure [3]). Furthermore, changing a -CF3 (or -C2F5) group with a PhF2C induces a significant charge inversion on sp-carbon atoms. To further understand the origin of the regio­selectivity of this hydrogermylation reaction by using AlCl3 as catalyst, a similar charge analysis was carried out on intermediates (1a′, 1b′ and 1c′). By looking at the partial charge of each carbocation, it seems that C3 of 1c′ is less electrophile than those of 1a′ and 1b′. This may explain the higher regioselectivity observed in the case of alkynes 1a and 1b (Figure [3]).

Zoom Image
Figure 3 Partial charges on the sp-carbon atoms

By taking into consideration the charge distribution of these two sp-carbon atoms, a plausible ionic mechanism for the AlCl3-catalyzed cis hydrogermylation of fluorinated alkynes type 1 is shown in Scheme [5]. The coordination of the ester-carbonyl group of alkynes of type 1 to AlCl3 produces the zwitterionic intermediate I, which is transformed into allenoate II through hydride transfer from Ph3GeH to the cationic center of I. Trapping of intermediate II with germylium-type species occurs from the less hindered face, cis to H, thus providing the cis-hydrogermylation (E)-α products and regenerating the AlCl3 catalyst.

Zoom Image
Scheme 5 Plausible Mechanism for cis-hydrogermylation of fluorinated alkynes 1

In summary, the AlCl3-catalyzed hydrogermylation reaction of ethyl propiolate bearing a perfluoroalkyl group can be achieved under very mild conditions. This reaction proceeds in a highly regio- and stereocontrolled manner, providing functionalized vinylgermane products with excellent yields. Studies are now under way to delineate the synthetic utility of these reagents and the results of these investigations will be reported in due course.

Most reagents were obtained from commercial sources and used as received. All reactions were carried out under inert atmosphere. ­Petroleum ether (PE) used had a boiling range 40–60 °C, CH2Cl2 was distilled from calcium hydride and stored under Argon. Thin-layer chromatography (TLC) was performed on Merck 60F254 plates. Column chromatography was carried out with Merck silica gel 60 (0.040–0.063 mm, 230–400 mesh). All 1H, 13C, and 19F NMR spectra were recorded with a 300 MHz Bruker Avance FT NMR spectrometer (300 MHz, 75 or 282 MHz, respectively). All chemical shifts are given as δ values (ppm) with reference to tetramethylsilane (TMS) as an internal standard. The peak patterns are indicated as follows: s, singlet; d, doublet; t, triplet; q, quartet; m, multiplet. The coupling constants J are reported in Hertz (Hz). Electrospray ionization high-resolution mass spectrometry experiments (HRMS) were performed with a hybrid tandem quadrupole/time-of flight (Q-TOF) instrument, equipped with a pneumatically assisted electrospray (Z-spray) ion source (Micro­mass, Manchester, U.K.) operated in positive mode.

AlCl3-Catalyzed Hydrogermylation Reaction: Synthesis of (E)-α ­Adduct; General Procedure A

Alkyne 1a (143 mg, 0.86 mmol) was placed in a vial containing a magnetic stirring bar. AlCl3 (12 mg, 0.09 mmol, 10 mol%) in CH2Cl2 (0.5 mL) was added to the vial. The vial was sealed with a Teflon-coated silicon rubber septum, evacuated and filled with argon. The reaction mixture was set at 0 °C. After 5 min stirring, Ph3GeH (220 mg, 0.72 mmol) was then added. The mixture was stirred for 1 hour at 0 °C, then Et3N (37 mg, 0.36 mmol) was added. The reaction mixture was allowed to warm to r.t. then hexane was added and the mixture was filtered through Celite. The solvent was evaporated under vacuum and column chromatography through silica gel afforded the purified (E)--isomer (290 mg, 92%) with complete regio- and stereoselectivity.

Radical Hydrogermylation using BEt3: Synthesis of Mixture of ­Isomers (E)-β, (Z)-β, (E)-α, (Z)-α; General Procedure B

Triethylborane (6 mg, 0.1 equiv, 0.06 mmol), Bu3GeH (177 mg, 1.2 equiv, 0.72 mmol) and CH2Cl2 (0.4 mL) were placed in a vial containing a magnetic stirring bar. The vial was sealed with a teflon-coated silicon rubber septum, evacuated and filled with argon. Alkyne 1a (100 mg, 1 equiv, 0.60 mmol) was added slowly to the reaction mixture. The reaction mixture was left for 3 hours under agitation at r.t. then the solvent was evaporated under vacuum. Column chromato­graphy through silica gel using PE as eluent afforded the four isomers (247 mg, 50% overall yield).

(E)-, (E)-, (E)- and (E)- were characterized by 1H, 13C, and 19F NMR and HRMS; whereas, all other products obtained in the form of a mixture of isomers were characterized at least by 1H NMR and 19F NMR spectroscopy.

(E)-Ethyl 4,4,4-Trifluoro-2-(triphenylgermyl)but-2-enoate [(E)-2α]

(E)- was obtained as the sole product by following general procedure A.

Yield: 92%; white solid; mp 85–86 °C.

1H NMR (300 MHz, CDCl3): δ = 7.67–7.46 (m, 15 H), 5.88 (q, J H–F = 7.2 Hz, 1 H), 4.07 (q, J = 7.1 Hz, 2 H), 1.02 (t, J = 7.1 Hz, 3 H).

13C NMR (CDCl3, 75 MHz): δ = 168.3, 146.4 (q, J C–F = 4.7 Hz), 135.3 (6C), 132.9 (3C), 130.1 (3C), 129.5 (q, J C–F = 35.2 Hz), 128.7 (6C), 121.3 (q, J C–F = 272.5 Hz), 61.4, 13.8.

19F NMR (CDCl3, 282 MHz): δ = –61.84.

HRMS (ESI): m/z [M + H]+ calcd for C24H22F3GeO2: 473.02904; found: 473.02710.

(E)-Ethyl 4,4,4-Trifluoro-3-(triphenylgermyl)but-2-enoate [(E)-2β]

(E)- was obtained as a mixture with the other three isomers by following general procedure B.

1H NMR (CDCl3, 300 MHz): δ = 7.66–7.34 (m, 15 H), 6.41 (bs, 1 H), 4.24 (q, J = 7.1 Hz, 2 H), 1.30 (t, J = 7.1 Hz, 3 H).

19F NMR (CDCl3, 282 MHz): δ = –54.58.

(Z)-Ethyl 4,4,4-Trifluoro-2-(triphenylgermyl)but-2-enoate [(Z)-2α]

(Z)- was obtained as a mixture with the other three isomers by following general procedure B.

1H NMR (CDCl3, 300 MHz): δ = 7.67–7.46 (m, 15 H), 6.99 (q, J H–F = 7.9 Hz, 1 H), 3.72 (q, J = 7.1 Hz, 2 H), 0.87 (t, J = 7.1 Hz, 3 H).

13C NMR (CDCl3, 75 MHz): δ = 169.6, 146.9 (q, J C–F = 5.3 Hz), 135.7 (6C), 134.3 (q, J C–F = 35.8 Hz), 133.2 (3C), 129.5 (3C), 128.7 (6C), 121.3 (q, J C–F = 272.5 Hz), 61.4, 13.8.

19F NMR (CDCl3, 282 MHz): δ = –60.5.

(Z)-Ethyl 4,4,4-Trifluoro-3-(triphenylgermyl)but-2-enoate [(Z)-2β]

(Z)- was obtained as a mixture with the other three isomers by following general procedure B.

1H NMR (CDCl3, 300 MHz): δ = 7.66–7.34 (m, 15 H), 7.26 (q, J H–F = 2.2 Hz, 1 H), 3.50 (q, J = 7.1 Hz, 2 H), 0.77 (t, J = 7.1 Hz, 3 H).

13C NMR (CDCl3, 75 MHz): δ = 164.5, 144.6 (q, J C–F = 31.1 Hz), 137.8 (q, J C–F = 8.8 Hz), 134.9 (6C), 129.3 (3C), 128.4 (6C), 128.4 (3C), 125.0 (q, J C–F = 272.8 Hz), 61.3, 13.4.

19F NMR (CDCl3, 282 MHz): δ = –60.7.

(E)-Ethyl 4,4,4-Trifluoro-2-(tributylgermyl)but-2-enoate [(E)-3α]

(E)- was obtained as a mixture with (Z)- by following general procedure A.

Yield: 89%; colorless oil.

1H NMR (CDCl3, 300 MHz): δ = 5.71 (q, J H–F = 7.23 Hz, 1 H), 4.22 (q, J = 7.1 Hz, 2 H), 1.38–1.28 (m, 18 H), 0.95–0.87 (m, 12 H).

13C NMR (CDCl3, 75 MHz): δ = 169.3, 149.2 (q, J C–F = 4.6 Hz), 125.3 (q, J C–F = 33.6 Hz), 121.4 (q, J C–F = 272.3 Hz), 68.1, 26.8 (3C), 26.4 (3C), 14.2, 13.7 (3C), 12.6 (3C).

19F NMR (CDCl3, 282 MHz): δ = –61.93.

HRMS (ESI): m/z [M + H]+calcd for C18H34F3GeO2: 413.02930; found: 413.02721.

(E)-Ethyl 4,4,4-Trifluoro-3-(tributylgermyl)but-2-enoate [(E)-3β]

(E)- was obtained as a mixture with the other three isomers by following general procedure B.

1H NMR (CDCl3, 300 MHz): δ = 6.35 (q, J H–F = 1.7 Hz, 1 H), 4.22 (q, J= 7.1 Hz, 2 H), 1.38–1.28 (m, 18 H), 0.95–0.87 (m, 12 H).

19F NMR (CDCl3, 282 MHz): δ = –61.63.

(Z)-Ethyl 4,4,4-Trifluoro-2-(tributylgermyl)but-2-enoate [(Z)-3α]

(Z)-3α was obtained as a mixture with (E)-3α by following general procedure A.

1H NMR (CDCl3, 300 MHz): δ = 6.61 (q, J H–F = 8.5 Hz, 1 H), 4.22 (q, J = 7.1 Hz, 2 H), 1.38–1.28 (m, 18 H), 0.95–0.87 (m, 12 H).

13C NMR (CDCl3, 75 MHz): δ = 170.6, 150.3 (q, J C–F = 5.5 Hz), 132.6 (q, J C–F = 35.5 Hz), 122.9 (q, J C–F= 269.8 Hz), 61.5, 27.1 (3C), 25.7 (3C), 14.2 (3C), 14.0, 13.9 (3C).

19F NMR (CDCl3, 282 MHz): δ = –60.50.

(Z)-Ethyl 4,4,4-Trifluoro-3-(tributylgermyl)but-2-enoate [(Z)-3β]

(Z)- was obtained as a mixture with the other three isomers by following general procedure B.

1H NMR (CDCl3, 300 MHz): δ = 6.89 (q, J H–F = 2.3 Hz, 1 H), 4.23 (q, J = 7.1 Hz, 2 H), 1.38–1.28 (m, 18 H), 0.95–0.87 (m, 12 H).

13C NMR (CDCl3, 75 MHz): δ = 165.4, 150.2 (q, J C–F = 31.3 Hz), 134.5 (q, J C–F = 9.6 Hz), 125.6 (q, J C–F= 272.5 Hz), 61.1, 27.1 (3C), 26.3 (3C), 14.1, 13.6 (3C), 13.4 (3C).

19F NMR (CDCl3, 282 MHz): δ = –61.76.

(E)-Ethyl 4,4,5,5,5-Pentafluoro-2-(triphenylgermyl)pent-2-enoate [(E)-4α]

(E)- was obtained as a sole product by following general procedure A.

Yield: 91%; white solid; mp 85–86 °C.

1H NMR (CDCl3, 300 MHz): δ = 7.54–7.39 (m, 15 H), 5.80 (t, J H–F = 13.3 Hz, 1 H), 3.95 (q, J = 7.1 Hz, 2 H), 1.0 (t, J = 7.1 Hz, 3 H).

13C NMR (CDCl3, 75 MHz): δ = 168.3, 145.2 (t, J C–F = 4.8 Hz), 135.6 (6C), 132.7 (3C), 130.1 (3), 128.7 (6C), 126.8 (t, J C–F = 23.4 Hz), 118.8 (qt, J C–F = 284.7 Hz, 36.7 Hz), 111.6 (tq, J C–F = 252.8 Hz, 38.8 Hz), 61.3, 13.8.

19F NMR (CDCl3, 282 MHz): δ = –84.55 (t, J F–F = 2.0 Hz, CF3), –113.96 (q, J F–F = 2.0 Hz, CF2).

HRMS (ESI): m/z [M + H]+ calcd for C25H22F5GeO2: 523.07463; found: 523.07265.

(E)-Ethyl 4,4,5,5,5-Pentafluoro-3-(triphenylgermyl)pent-2-enoate [(E)-4β]

(E)- was obtained as a mixture with the other three isomers by following general procedure B.

1H NMR (CDCl3, 300 MHz): δ = 7.66–7.3 (m, 15 H), 6.66 (t, J H–F = 1.7 Hz, 1 H), 4.28 (q, J = 7.1 Hz, 2 H), 0.86 (t, J = 7.1 Hz, 3 H).

19F NMR (CDCl3, 282 MHz): δ = –81.61 (t, J F–F = 2.2 Hz, CF3), –102.14 (q, J F–F = 2.2 Hz, CF2).

(Z)-Ethyl 4,4,5,5,5-Pentafluoro-2-(triphenylgermyl)pent-2-enoate [(Z)-4α]

(Z)- was obtained as a mixture with the other three isomers by following general procedure B.

1H NMR (CDCl3, 300 MHz): δ = 7.66–7.3 (m, 15 H), 5.89 (t, J H–F = 14.2 Hz, 1 H), 4.03 (q, J = 7.1 Hz, 2 H), 1.06 (t, J = 7.1 Hz, 3 H).

19F NMR (CDCl3, 282 MHz): δ = –84.59 (t, J F–F = 2.2 Hz, CF3), –113.89 (q, J F–F = 2.2 Hz, CF2).

(Z)-Ethyl 4,4,5,5,5-Pentafluoro-3-(triphenylgermyl)pent-2-enoate [(Z)-4β]

(Z)- was obtained as a mixture with the other three isomers by following general procedure B.

1H NMR (CDCl3, 300 MHz): δ = 7.66–7.3 (m, 15 H), 7.32 (t, J H–F = 1.9 Hz, 1 H), 3.48 (q, J = 7.1 Hz, 2 H), 1.01 (t, J = 7.1 Hz, 3 H).

19F NMR (CDCl3, 282 MHz): δ = –82.06 (t, J F–F = 2.3 Hz, CF3), –104.78 (q, J F–F = 2.3 Hz, CF2).

(E)-Ethyl 4,4,5,5,5-Pentafluoro-2-(tributylgermyl)pent-2-enoate [(E)-5α]

(E)- was obtained as a mixture with (Z)- by following general procedure A.

Yield: 84%; colorless oil.

1H NMR (CDCl3, 300 MHz): δ = 5.60 (t, J H–F = 13.3 Hz, 1 H), 4.21 (q, J = 7.1 Hz, 2 H), 1.38–1.25 (m, 12 H), 0.97–0.86 (m, 18 H).

13C NMR (CDCl3, 75 MHz): δ = 169.4, 152.2 (t, J C–F = 4.7 Hz), 122.4 (t, J C–F = 23.5 Hz), 111.6 (tq, J C–F = 252/ 38.5 Hz), 118.9 (qt, J C–F = 284.5/ 37.1 Hz), 61.0, 26.8 (3C), 26.3 (3C), 14.2, 13.7 (3C), 12.6 (3C).

19F NMR (CDCl3, 282 MHz): δ = –84.91 (t, J F–F = 2.2 Hz, CF3), –113.95 (q, J F–F = 2.2 Hz, CF2).

HRMS (ESI): m/z [M + H]+ calcd for C19H34F5GeO2: 463.16853; found: 463.16643.

(E)-Ethyl 4,4,5,5,5-Pentafluoro-3-(tributylgermyl)pent-2-enoate [(E)-5β]

(E)- was obtained as a mixture with the other three isomers by following general procedure B.

1H NMR (CDCl3, 300 MHz): δ = 6.31 (bs, 1 H), 4.21 (q, J = 7.1 Hz, 2 H), 1.38–1.25 (m, 18 H), 0.97–0.86 (m, 12 H).

19F NMR (CDCl3, 282 MHz): δ = –82.76 (t, J F–F = 1.8 Hz, CF3), –113.91 (q, J F–F = 1.8 Hz, CF2).

(Z)-Ethyl 4,4,5,5,5-Pentafluoro-2-(tributylgermyl)pent-2-enoate [(Z)-5α]

(Z)- was obtained as a mixture with (E)- by following general procedure A.

1H NMR (CDCl3, 300 MHz): δ = 6.50 (t, J H–F = 14.8 Hz, 1 H), 4.21 (q, J = 7.1 Hz, 2 H), 1.38–1.25 (m, 18 H), 0.97–0.86 (m, 12 H).

19F NMR (CDCl3, 282 MHz): δ = –84.95 (t, J F–F = 2.5 Hz, CF3), –113.46 (q, J F–F = 2.5 Hz, CF2).

(Z)-Ethyl 4,4,5,5,5-Pentafluoro-3-(tributylgermyl)pent-2-enoate [(Z)-5β]

(Z)- was obtained as a mixture with the other three isomers by following general procedure B.

1H NMR (CDCl3, 300 MHz): δ = 6.84 (t, J H–F = 2.0 Hz, 1 H), 4.21 (q, J = 7.1 Hz, 2 H), 1.38–1.25 (m, 18 H), 0.97–0.86 (m, 12 H).

19F NMR (CDCl3, 282 MHz): δ = –82.29 (t, J F–F = 1.5 Hz, CF3), –105.48 (q, J F–F = 1.5 Hz, CF2).

(E)-Methyl 4,4-Difluoro-4-phenyl-2-(triphenylgermyl)but-2-enoate [(E)-6α]

(E)- was obtained as a mixture with the other three isomers by following general procedure A.

1H NMR (CDCl3, 300 MHz): δ = 7.61–7.25 (m, 15 H), 7.23–7.17 (m, 2 H), 7.19–7.09 (m, 2 H), 7.08 (t, J = 14.0 Hz, 1 H), 6.88–6.86 (m, 1 H), 3.04 (s, 3 H).

13C NMR (CDCl3, 75 MHz): δ = 165.8, 152.7 (t, J C–F = 29.5 Hz), 142.2 (t, J C–F = 29.8 Hz), 135.9 (t, J C–F = 2.4 Hz, 2C), 134.9 (6C), 129.9 (t, J C–F = 1.3 Hz, 2C), 129.6, 129.1 (3C), 128.1 (3C), 127.9 (6C), 125.7 (t, J C–F = 5.6 Hz, 1C), 122.23 (t, J C–F = 242.2 Hz, 1C, CF2), 51.4.

19F NMR (CDCl3, 282 MHz): δ = –85.31.

(E)-Methyl 4,4-Difluoro-4-phenyl-3-(triphenylgermyl)but-2-enoate [(E)-6β]

(E)- was obtained as a mixture with the other three isomers by following general procedure A.

1H NMR (CDCl3, 300 MHz): δ = 7.61–7.25 (m, 15 H), 7.23–7.17 (m, 2 H), (m, 2 H), 7.19–7.09 (m, 2 H), 6.40 (t, J = 1.7 Hz, 1 H), 6.88–6.86 (m, 1 H), 3.59 (s, 3 H).

19F NMR (CDCl3, 282 MHz): δ = –91.30.

(Z)-Methyl 4,4-Difluoro-4-phenyl-2-(triphenylgermyl)but-2-enoate [(Z)-6α]

(Z)- was obtained as a mixture with the other three isomers by following general procedure A.

1H NMR (CDCl3, 300 MHz): δ = 7.61–7.25 (m, 15 H), 7.23–7.17 (m, 2 H), (m, 2 H), 7.19–7.09 (m, 2 H), 6.05 (t, J = 12.1 Hz, 1 H), 6.88–6.86 (m, 1 H), 3.46 (s, 3 H).

19F NMR (CDCl3, 282 MHz): δ = –78.11.

(Z)-Methyl 4,4-Difluoro-4-phenyl-3-(triphenylgermyl)but-2-enoate [(Z)-6β]

(Z)- was obtained as a mixture with the other three isomers by following general procedure A.

1H NMR (CDCl3, 300 MHz): δ = 7.61–7.25 (m, 15 H), 7.23–7.17 (m, 2 H), (m, 2 H), 7.19–7.09 (m, 2 H), 7.13 (t, J = 2.7 Hz, 1 H), 6.88–6.86 (m, 1 H), 3.20 (s, 3 H).

19F NMR (CDCl3, 282 MHz): δ = –90.26.


#
#

Acknowledgment

We would like to thank the Association of Specialization and Scientific Orientation (Lebanon) and Lebanese University for their support. We thank also the Département d’analyses Chimiques et Médicales (Tours, France) for chemical analyses.

Supporting Information

  • References

  • 2 Dinoiu V. Rev. Roum. Chim. 2006; 51: 1141
  • 3 The Practice of Medicinal Chemistry . Wermuth C. Academic Press; London: 1996: 203
    • 4a Smart BE. Chem. Rev. 1996; 96: 1555
    • 4b Banks RE, Smart BE, Tatlow JC. Organofluorine Chemistry: Principle and Commercial Application . Plenum Press; New York: 1994
    • 4c van Niel MB, Collins I, Beer MS, Broughton HB, Cheng SK. F, Goodacre SC, Heald A, Locker KL, MacLeod AM, Morrison D, Moyes CR, O’Connor D, Pike A, Rowley M, Russell MG. N, Sohal B, Stanton JA, Thomas S, Verrier H, Watt AP, Castro JL. J. Med. Chem. 1999; 42: 2087
    • 4d Arnone A, Bravo P, Donadelli A, Resnati G. Tetrahedron 1996; 52: 131
    • 5a Zhou P, Qian L, Kozopas KM, Craig RW. Blood 1997; 89: 630
    • 5b Zhou Q, Salvesen GS. J. Biol. Chem. 1997; 324: 361
    • 5c Zhou Q, Snipas S, Orth K, Muzio M, Dixit VM, Salvesen GS. J. Biol. Chem. 1997; 272: 7797
    • 6a Thompson CB. Science 1995; 267: 1456
    • 6b Altmann KH, Pfeiffer B, Arseniyadis S, Pratt BA, Nicolaou KC. ChemMedChem 2007; 2: 396
  • 7 Kobayashi T, Eda T, Tamura O, Ishibashi H. J. Org. Chem. 2002; 67: 3156
  • 8 Besset T, Poisson T, Pannecoucke X. Chem. Eur. J. 2014; 20: 16830
  • 10 Bowman WR, Krintel SL, Schilling MB. Org. Biomol. Chem. 2004; 2: 585
  • 11 Wolfsberger W. J. Prakt. Chem. 1992; 334: 453
    • 12a Esteruelas MA, Martín M, Oro LA. Organometallics 1999; 18: 2267
    • 12b Kinoshita H, Nakamura T, Kakiya H, Shinokubo H, Matsubara S, Oshima K. Org. Lett. 2001; 3: 2521
    • 12c Faller JW, Kultyshev RG. Organometallics 2003; 22: 199
    • 12d Matsuda T, Kadowaki S, Yamaguchi Y, Murakami M. Org. Lett. 2010; 12: 1056
    • 12e Ichinose Y, Nozaki K, Wakamatsu K, Oshima K, Utimoto K. Tetrahedron Lett. 1987; 28: 3709
    • 12f Corriu RJ. P, Moreau JJ. E. J. Chem. Soc. D 1971; 812
    • 12g Wada F, Abe S, Yonemaru N, Kikukawa K, Matsuda T. Bull. Chem. Soc. Jpn. 1991; 64: 1701
    • 12h Lukevics E, Barabanov DI, Ignatovich LM. Appl. Organomet. Chem. 1991; 5: 379
  • 13 Prié G, Thibonnet J, Abarbri M, Duchêne A, Parrain J.-L. Synlett 1998; 839
  • 14 Carcenac Y, Zine K, Kizirian JC, Thibonnet J, Duchêne A, Parrain J.-L, Abarbri M. Adv. Synth. Catal. 2010; 352: 949
    • 15a Thibonnet J, Duchêne A, Parrain J.-L, Abarbri M. J. Org. Chem. 2004; 69: 4262
    • 15b David-Quillot F, Thibonnet J, Marsacq D, Abarbri M, Duchêne A. Tetrahedron Lett. 2000; 41: 9981
  • 16 Palmas P, Thibonnet J, Parrain J.-L, Abarbri M, David-Quillot F, Duchêne A. Magn. Reson. Chem. 2002; 40: 537
  • 17 Besset T, Poisson T, Pannecoucke X. Chem. Eur. J. 2014; 20: 16830
  • 18 Konno T. Synlett 2014; 25: 1350
  • 19 Jacquet J, Blanchard S, Derat E, Murr MD.-E, Fensterbank L. Chem. Sci. 2016; 7: 2030
  • 20 Schweizer S, Tresse C, Bisseret P, Lalevée J, Evano G, Blanchard N. Org. Lett. 2015; 17: 1794
  • 21 Minisci F, Citterio A, Giordano C. Acc. Chem. Res. 1983; 16: 27
    • 22a Nozaki K, Oshima K, Uchimoto K. J. Am. Chem. Soc. 1987; 109: 2547
    • 22b Nozaki K, Oshima K, Utimoto K. Tetrahedron 1989; 45: 923
    • 22c Satoh S, Sodeoka M, Sasai H, Shibasaki M. J. Org. Chem. 1991; 56: 2278
    • 22d Lowinger TB, Weiler L. J. Org. Chem. 1992; 57: 6099
    • 22e Guindon Y, Jung G, Guérin B, Ogilvie WW. Synlett 1998; 213
    • 22f Shuto S, Kanazaki M, Ichikawa S, Matsuda A. J. Org. Chem. 1997; 62: 5676
    • 22g Sibi MP, Shay J, Ji J. Tetrahedron Lett. 1997; 38: 5955
    • 22h Miyabe H, Shibata R, Ushiro C, Naito T. Tetrahedron Lett. 1998; 39: 631
    • 22i Devin P, Fensterbank L, Malacria M. Tetrahedron Lett. 1998; 39: 833
  • 23 Schwier T, Gevorgyan V. Org. Lett. 2005; 7: 5191

    • For Lewis acid catalyzed hydrosilylation, see:
    • 24a Kato N, Tamura Y, Kashiwabara T, Sanji T, Tanaka M. Organometallics 2010; 29: 5274
    • 24b Liu Y, Yamazaki S, Yamabe S. J. Org. Chem. 2005; 70: 556 ; For Lewis acid catalyzed hydrostannylation, see
    • 24c Asao N, Liu J.-X, Sudoh T, Yamamoto Y. J. Org. Chem. 1996; 62: 4568
    • 24d Asao N, Liu J.-X, Sudoh T, Yamamoto Y. J. Chem. Soc., Chem. Commun. 1995; 2405
  • 25 Khalaf A, Grée D, Abdallah H, Jaber N, Hachem A, Grée R. Tetrahedron 2011; 67: 3881
  • 26 Reed AE, Weinstock RB, Weinhold F. J. Chem. Phys. 1998; 83: 735

  • References

  • 2 Dinoiu V. Rev. Roum. Chim. 2006; 51: 1141
  • 3 The Practice of Medicinal Chemistry . Wermuth C. Academic Press; London: 1996: 203
    • 4a Smart BE. Chem. Rev. 1996; 96: 1555
    • 4b Banks RE, Smart BE, Tatlow JC. Organofluorine Chemistry: Principle and Commercial Application . Plenum Press; New York: 1994
    • 4c van Niel MB, Collins I, Beer MS, Broughton HB, Cheng SK. F, Goodacre SC, Heald A, Locker KL, MacLeod AM, Morrison D, Moyes CR, O’Connor D, Pike A, Rowley M, Russell MG. N, Sohal B, Stanton JA, Thomas S, Verrier H, Watt AP, Castro JL. J. Med. Chem. 1999; 42: 2087
    • 4d Arnone A, Bravo P, Donadelli A, Resnati G. Tetrahedron 1996; 52: 131
    • 5a Zhou P, Qian L, Kozopas KM, Craig RW. Blood 1997; 89: 630
    • 5b Zhou Q, Salvesen GS. J. Biol. Chem. 1997; 324: 361
    • 5c Zhou Q, Snipas S, Orth K, Muzio M, Dixit VM, Salvesen GS. J. Biol. Chem. 1997; 272: 7797
    • 6a Thompson CB. Science 1995; 267: 1456
    • 6b Altmann KH, Pfeiffer B, Arseniyadis S, Pratt BA, Nicolaou KC. ChemMedChem 2007; 2: 396
  • 7 Kobayashi T, Eda T, Tamura O, Ishibashi H. J. Org. Chem. 2002; 67: 3156
  • 8 Besset T, Poisson T, Pannecoucke X. Chem. Eur. J. 2014; 20: 16830
  • 10 Bowman WR, Krintel SL, Schilling MB. Org. Biomol. Chem. 2004; 2: 585
  • 11 Wolfsberger W. J. Prakt. Chem. 1992; 334: 453
    • 12a Esteruelas MA, Martín M, Oro LA. Organometallics 1999; 18: 2267
    • 12b Kinoshita H, Nakamura T, Kakiya H, Shinokubo H, Matsubara S, Oshima K. Org. Lett. 2001; 3: 2521
    • 12c Faller JW, Kultyshev RG. Organometallics 2003; 22: 199
    • 12d Matsuda T, Kadowaki S, Yamaguchi Y, Murakami M. Org. Lett. 2010; 12: 1056
    • 12e Ichinose Y, Nozaki K, Wakamatsu K, Oshima K, Utimoto K. Tetrahedron Lett. 1987; 28: 3709
    • 12f Corriu RJ. P, Moreau JJ. E. J. Chem. Soc. D 1971; 812
    • 12g Wada F, Abe S, Yonemaru N, Kikukawa K, Matsuda T. Bull. Chem. Soc. Jpn. 1991; 64: 1701
    • 12h Lukevics E, Barabanov DI, Ignatovich LM. Appl. Organomet. Chem. 1991; 5: 379
  • 13 Prié G, Thibonnet J, Abarbri M, Duchêne A, Parrain J.-L. Synlett 1998; 839
  • 14 Carcenac Y, Zine K, Kizirian JC, Thibonnet J, Duchêne A, Parrain J.-L, Abarbri M. Adv. Synth. Catal. 2010; 352: 949
    • 15a Thibonnet J, Duchêne A, Parrain J.-L, Abarbri M. J. Org. Chem. 2004; 69: 4262
    • 15b David-Quillot F, Thibonnet J, Marsacq D, Abarbri M, Duchêne A. Tetrahedron Lett. 2000; 41: 9981
  • 16 Palmas P, Thibonnet J, Parrain J.-L, Abarbri M, David-Quillot F, Duchêne A. Magn. Reson. Chem. 2002; 40: 537
  • 17 Besset T, Poisson T, Pannecoucke X. Chem. Eur. J. 2014; 20: 16830
  • 18 Konno T. Synlett 2014; 25: 1350
  • 19 Jacquet J, Blanchard S, Derat E, Murr MD.-E, Fensterbank L. Chem. Sci. 2016; 7: 2030
  • 20 Schweizer S, Tresse C, Bisseret P, Lalevée J, Evano G, Blanchard N. Org. Lett. 2015; 17: 1794
  • 21 Minisci F, Citterio A, Giordano C. Acc. Chem. Res. 1983; 16: 27
    • 22a Nozaki K, Oshima K, Uchimoto K. J. Am. Chem. Soc. 1987; 109: 2547
    • 22b Nozaki K, Oshima K, Utimoto K. Tetrahedron 1989; 45: 923
    • 22c Satoh S, Sodeoka M, Sasai H, Shibasaki M. J. Org. Chem. 1991; 56: 2278
    • 22d Lowinger TB, Weiler L. J. Org. Chem. 1992; 57: 6099
    • 22e Guindon Y, Jung G, Guérin B, Ogilvie WW. Synlett 1998; 213
    • 22f Shuto S, Kanazaki M, Ichikawa S, Matsuda A. J. Org. Chem. 1997; 62: 5676
    • 22g Sibi MP, Shay J, Ji J. Tetrahedron Lett. 1997; 38: 5955
    • 22h Miyabe H, Shibata R, Ushiro C, Naito T. Tetrahedron Lett. 1998; 39: 631
    • 22i Devin P, Fensterbank L, Malacria M. Tetrahedron Lett. 1998; 39: 833
  • 23 Schwier T, Gevorgyan V. Org. Lett. 2005; 7: 5191

    • For Lewis acid catalyzed hydrosilylation, see:
    • 24a Kato N, Tamura Y, Kashiwabara T, Sanji T, Tanaka M. Organometallics 2010; 29: 5274
    • 24b Liu Y, Yamazaki S, Yamabe S. J. Org. Chem. 2005; 70: 556 ; For Lewis acid catalyzed hydrostannylation, see
    • 24c Asao N, Liu J.-X, Sudoh T, Yamamoto Y. J. Org. Chem. 1996; 62: 4568
    • 24d Asao N, Liu J.-X, Sudoh T, Yamamoto Y. J. Chem. Soc., Chem. Commun. 1995; 2405
  • 25 Khalaf A, Grée D, Abdallah H, Jaber N, Hachem A, Grée R. Tetrahedron 2011; 67: 3881
  • 26 Reed AE, Weinstock RB, Weinhold F. J. Chem. Phys. 1998; 83: 735

Zoom Image
Scheme 1 Previously described hydrostannylation of ethyl 4,4,4-tri­fluorobutenoate (1a)
Zoom Image
Figure 1 3 J H–F and 4 J H–F coupling constants of the two regioisomers α and β, respectively
Zoom Image
Figure 2 E- and Z- configuration assignments of the two regioisomers α and β
Zoom Image
Scheme 2 Hydrogermylation reactions of 1a using Bu3GeH
Zoom Image
Scheme 3 Hydrogermylation of 1b using Ph3GeH and Bu3GeH
Zoom Image
Scheme 4 AlCl3-catalyzed hydrogermylation of 1c using Ph3GeH
Zoom Image
Figure 3 Partial charges on the sp-carbon atoms
Zoom Image
Scheme 5 Plausible Mechanism for cis-hydrogermylation of fluorinated alkynes 1