This work was supported by the National Nature Science Foundation of China (21502023).

1. Synthesis of 1-(Iodoethynyl)-4-Methylbenzene (2, 1-Iodoalkynes)
<ol>
	<li>Add 133 mg (0.36 mmol) of TBAI and 3 mL of CH3CN to a reaction tube that contains a magnetic stirring bar, which is open to air. Then, add 38 &#956;L (0.3 mmol) of p-tolylethyne to the mixture using a microsyringe.</li>
	<li>Add 96.6 mg (0.3 mmol) of PIDA to the vigorously stirred reaction mixture in 10 portions over a period of 20 min using a spatula.</li>
	<li>Stir the reaction mixture at room temperature for 3 h.</li>
	<li>Pour the resulting mixture into a separatory funnel that contains 30 mL of water, and quench with aqueous Na2S2O3 (10%, 0.5 mL). Extract the aqueous layer three times with 10 mL of ethyl acetate.</li>
	<li>Wash the combined organic layers with 10 mL of saturated brine and dry over anhydrous sodium sulfate (0.5 g).</li>
	<li>Filter off the sodium sulfate using a Buchner funnel, and concentrate the filtrate under reduced pressure to obtain the crude product.</li>
	<li>Purify the crude product by column chromatography on silica gel using hexane as the eluent; the pure product, 1-(iodoethynyl)-4-methylbenzene, is obtained as a light yellow liquid (71.9 mg, 99% yield; Rf = 0.79).</li>
	<li>Analyze the product by 1H and 13C NMR spectroscopy, and high-performance liquid chromatography (HPLC).</li>
</ol>
2. Synthesis of (E)-1-(1,2-Diiodovinyl)-4-Methylbenzene (3, 1,2-Diiodoalkenes)
<ol>
	<li>Add 124.5 mg (0.75 mmol) of KI and 1 mL of CH3CN to a reaction tube that contains a magnetic stirring bar, which is open to air. Then, add 38 &#956;L (0.3 mmol) of p-tolylethyne and 3 mL of H2O to the mixture via a microsyringe.</li>
	<li>Add 96.6 mg (0.3 mmol) of PIDA to the vigorously stirred reaction mixture in 10 portions over a period of 20 min using a spatula.</li>
	<li>Stir the reaction mixture at room temperature for 24 h.</li>
	<li>Pour the resulting mixture into a separatory funnel that contains 30 mL of water, quench with aqueous Na2S2O3 (10%, 1 mL), and extract the aqueous layer three times with 10 mL of ethyl acetate.</li>
	<li>Wash the combined organic layers with 10 mL of brine and dry over anhydrous sodium sulfate (0.5 g).</li>
	<li>Filter off the sodium sulfate using a Buchner funnel, and concentrate the filtrate under reduced pressure to obtain the crude product.</li>
	<li>Purify the crude product by column chromatography on silica gel using hexane as the eluent. The pure product, (E)-1-(1,2-diiodovinyl)-4-methylbenzene, is obtained as a light yellow liquid (111.9 mg, 98% yield; Rf = 0.84).</li>
	<li>Analyze the product by 1H and 13C NMR spectroscopy as well as HPLC.</li>
</ol>
3. Synthesis of 1-Methyl-4-(1,2,2-Triiodovinyl)benzene (4, 1,1,2-Triiodoalkenes)
<ol>
	<li>Add 133 mg (0.36 mmol) of TBAI and 1 mL of CH3CN to a reaction tube that contains a stirring bar, which is open to air. Then, add 38 &#956;L (0.3 mmol) of p-tolylethyne using a microsyringe.</li>
	<li>Add 96.6 mg (0.3 mmol) of PIDA to the vigorously stirred reaction mixture in 10 portions over a period of 20 min using a spatula. Stir the reaction mixture for 3 h at room temperature.</li>
	<li>Add 124.5 mg (0.75 mmol) of KI in 3 mL of H2O to the reaction mixture.</li>
	<li>Add 193.2 mg (0.6 mmol) of PIDA to the reaction mixture in 10 portions over a period of 20 min using a spatula. Stir the reaction mixture for another 3 h at room temperature.</li>
	<li>Add another 124.5 mg (0.75 mmol) of KI in 3 mL of H2O and 1 mL of CH3CN to the reaction mixture.</li>
	<li>Add another 193.2 mg (0.6 mmol) of PIDA to the reaction mixture in 10 portions over a period of 20 min using a spatula. Stir the reaction mixture for another 12 h at room temperature.</li>
	<li>Pour the resulting mixture into a separatory funnel that contains 30 mL of water, quench with aqueous Na2S2O3 (10%, 2 mL), and extract the aqueous layer three times with 10 mL of ethyl acetate.</li>
	<li>Wash the combined organic layers with 10 mL of brine and dry over anhydrous sodium sulfate (0.5 g).</li>
	<li>Filter off the sodium sulfate using a Buchner funnel, and concentrate the filtrate under reduced pressure to obtain the crude product.</li>
	<li>Purify the crude product by column chromatography on silica gel using hexane to get the pure product, 1-methyl-4-(1, 2, 2-triiodovinyl)benzene, as a yellow liquid (138.4 mg, 93% yield; Rf = 0.79).</li>
	<li>Analyze the product by 1H and 13C NMR spectroscopy as well as HPLC.</li>
</ol>
4. Determination of the Selectivity for the Mono-, Di-, or Tri-iodination of Terminal Alkynes by HPLC
Note: The selectivity for the mono-, di-, tri-iodination of the alkynes was determined by HPLC. HPLC was performed on an instrument using a 5 &#956;m, 4.6 mm &#215; 150 mm column, CH3CN/H2O = 75/25 (v/v) as the solvent, a flow rate of 1.0 mL/min, and a detector wavelength of &#955; = 254 nm.
<ol>
	<li>Preparation of the external standard solution for HPLC
	<ol>
		<li>Precisely weigh out 2 (1-(iodoethynyl)-4-methylbenzene; 9.58 mg, 39.58&#215;10-3 mmol), 3 ((E)-1-(1,2-diiodovinyl)-4-methylbenzene; 19.29 mg, 52.14&#215;10-3 mmol), and 4 (1-methyl-4-(1,2,2-triiodovinyl)benzene; 11.10 mg, 22.38&#215;10-3 mmol).</li>
		<li>Mix and dissolve these three compounds in 1 mL of CH3CN and dilute the stock solution 100 times before performing the HPLC separation.</li>
		<li>Determine the peak area ratio (%) of each product on HPLC chromatogram.</li>
		<li>Calculate the ratio of the molar absorptivity of each compound according to the following formula: 
		&#949;2 : &#949;3 : &#949;4 = A2/n2 : A3/n3 : A4/n4 
		where &#949; is the molar absorptivity, A the peak area, and n the molar weight.</li>
	</ol>
	</li>
	<li>Calculate the chemoselectivity according to the following formula: 
	n2 : n3 : n4 = A2/&#949;2 : A3/&#949;3 : A4/&#949;4</li>
</ol>

The authors have nothing extraordinary to disclose.

1-Iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes can be chemoselectively synthesized using hypervalent-iodine reagents as efficient mediators for oxidative iodination(s). The most critical factors of these chemoselective iodination protocols are the nature and loading of the iodine source, as well as the solvent. For example, 1-iodoalkyne 2 was obtained as the major product (52% yield) when TBAI (2.5 equiv loading) was selected as the iodine source in combination with MeOH as the solvent (2:3:4= 90:5:5). When changing the iodine source to KI, such a selectivity was not observed, whereas using NH4I resulted in the predominant formation of 1,2-diiodoalkene 3. The details of the optimization of the reaction conditions are documented elsewhere36&#160;(Table 1).
Several attempts were made to identify the optimal conditions for the formation of 1-iodoalkynes36. Firstly, the TBAB loading greatly affects the selectivity towards 1-iodoalkyne 2. Lowering the TBAB loading from 2.5 to 1.2 equiv favors the formation of 2. Secondly, the nature of the solvent strongly influences the formation of 1-iodoalkyne 2 in terms of selectivity and yield. For example, CH3CN, Et2O, THF, and DCM favor the synthesis of 2 in terms of yield (excellent) and selectivity (absolute). DMF and toluene afford 2 in good yield, albeit with slightly lower selectivity. Notably, 1-iodoalkynes are most efficiently generated by treating the terminal alkyne (1.0 equiv) at room temperature for 2&#8722;24 h with PIDA (1.0 equiv) and TBAI (1.2 equiv) in CH3CN, THF, or Et2O.
Changing the solvent to a CH3CN-H2O mixture dramatically enhances the chemoselectivity towards 1,2-diiodoalkene 3, when using KI as the iodine source. Optimal reaction conditions for the preparation of 1,2-diiodoalkenes were established as follows: treating the terminal alkyne (1.0 equiv) at room temperature for 2&#8722;24 h with PIDA (1.0 equiv) and KI (2.5 equiv) in MeCN-H2O (1:3)36.
A practical one-pot synthesis of 1,1,2-triiodoalkene 4 can be realized by combining the two aforementioned methods. Typically, terminal 4-ethynytoluene (1.0 equiv), PIDA (1.0 equiv), and TBAI (1.2 equiv) were stirred for 3 h at room temperature, followed by adding PIDA and an aqueous KI solution. Under these reaction conditions, 4-ethynytoluene was fully consumed; however, only 44% transformation was observed when 1.0 equiv of PIDA was using in the second step. Extending the reaction time did not increase the transformation. Therefore, the loading of PIDA (2.0 equiv) was increased in the second step to accelerate this transformation, leading to the formation of 4 in 88% yield as a major product. Interestingly, with an additional portion of PIDA and KI, a further increase of the yield of 4 (93%) was observed. Therefore, the reaction conditions for the synthetic method of 4 were optimized. (i) The terminal alkyne (1.0 equiv) was mixed with PIDA (1.0 equiv) and TBAI (1.2 equiv) for 3 h at room temperature in MeCN; (ii) after the addition of H2O, PIDA (2.0 equiv), and KI (2.5 equiv), the reaction mixture was stirred for another 3 h; (iii) with the addition of H2O, PIDA (2.0 equiv), and KI (2.5 equiv), the reaction mixture was stirred for another 12 h36.
Herein, we have presented practical methods for the chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes based on the hypervalent-iodine catalyzed iodination of terminal alkynes. These methods feature high chemoselectivity, good yield, low toxicity, mild reaction conditions, and broad scope. We expect that these new synthetic methods can be applied to the efficient and chemoselective synthesis of more iodoalkyne derivatives, materials, intermediates, and biologically active compounds.

Iodoalkynes and iodoalkenes are widely used important precursors and building blocks in organic synthesis1,2,3,4, biologically active substances, and useful in the synthesis of materials and complex molecules given the ease of converting the C-I bond5,6,7,8. In recent years, the oxidative iodination of terminal alkynes has attracted more attention to the synthesis of iodoalkyne and iodoalkene derivatives. So far, efficient methods that use metal catalysts9,10,11,12, hypervalent-iodonium catalysts13,14, an anodic oxidation system15, ionic liquid systems16, KI (or I2)-oxidant combinations17,18,19,20, ultrasound21, phase-transfer catalysts22, N-iodosuccinimide9,22,23,24,25, n-BuLi26,27,28,29,30,31, Grignard reagents32, and morpholine catalysts17,33,24,35&#160;have been developed for the iodination of alkynes. Recently, we have reported a practical and chemoselective protocol for the synthesis of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes36. The features of this method are green and practical: (1) the toxicity of hypervalent-iodine catalysts as oxidative functionalization reagents is low compared to other conventional heavy-metal-based oxidants37,38,39,40,41,42, and (2) TBAI and/or KI are used as iodine sources. In addition, our system affords excellent selectivity under mild conditions. The chemoselective synthesis of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes requires precise control over various factors, including the composition, the oxidant, the iodine source, and the solvent. Among these, the iodine source is the most important factor for the chemoselectivity of the reaction. After the screening of several types and loadings of the iodine source as well as the solvents, three methods were identified and established. Firstly, TBAI as an iodine source in combination with PIDA (TBAI-PIDA) is selective for the synthesis of 1-iodoalkynes. Alternatively, 1,2-diiodoalkenes are efficiently obtained using a KI-PIDA system. Both methods afford the corresponding products in high yield and high chemoselectivity. The corresponding tri-iodinationproducts, i.e., 1,1,2-triiodoalkenes, were obtained in good yield from the one-pot synthesis that combine the TBAI-PIDA and KI-PIDA systems36.
Here, we will demonstrate how the chemoselectivity for the iodination of terminal alkynes can be steered from 1-iodoalkynes to 1,2-diiodoalkenes and to 1,1,2-triiodoalkenes under similar reaction conditions, highlighting the precise control that can be exerted by judiciously choosing oxidant, iodine source, and solvent. For the development of this new synthetic technique, p-tolylethyne was used as a model substrate. Although the following protocols focus on the synthesis of 1-(iodoethynyl)-4-methylbenzene, (E)-1-(1,2-diiodovinyl)-4-methylbenzene, and 1-methyl-4-(1,2,2-triiodovinyl)benzene, these compounds are representative for 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes, respectively, i.e., the protocols are broad in scope, and the same techniques can be applied to the chemoselective iodination of aromatic and aliphatic terminal alkynes36.
Reagents employed in the chemoselective iodination of terminal alkynes and small deviations from the techniques described result in dramatic differences with respect to the target products. For instance, changing of iodine source from TBAI to KI and changing of solvent from CH3CN to a CH3CN-H2O has a dramatic impact on the chemoselectivity of the iodination. The detailed protocol aims at helping new practitioners in the field with the chemoselective iodination of terminal alkynes to avoid many common pitfalls during the synthesis of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

<table border="0" cellpadding="0" cellspacing="0" width="860">
	<tbody>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">4-ethynyltoluene,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">D080006</td>
			<td style="width:167px;"></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">phenylacetylene,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">W330041</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">1-ethynyl-4-methoxybenzene,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">D080007</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">1-ethynyl-4-fluorobenzene,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">D080005</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:263px;">4-(Trifluoromethyl)phenylacetylene,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">W320273</td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:263px;">4-Ethynylbenzoic acid methyl ester,97%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">A020720</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">3-Aminophenylacetylene,97%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">D080001</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">3-Butyn-1-ol,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">A040031</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">Propargylacetate,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">L10031</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">Tetrabutylammonium Iodide,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">E010070</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">Potassium iodide,98%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">E010364</td>
			<td></td>
		</tr>
		<tr height="40">
			<td height="40" style="height:40px;width:263px;">(diacetoxyiodo)benzene,99%</td>
			<td style="width:311px;">Energy Chemical</td>
			<td style="width:119px;">A020180</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">acetonitrile, HPLC grade</td>
			<td style="width:311px;">fischer</td>
			<td style="width:119px;">A998-4</td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">magnetic stirrer</td>
			<td style="width:311px;">IKA</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="21">
			<td height="21" style="height:21px;width:263px;">rotary evaporator</td>
			<td style="width:311px;">Buchi</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="63">
			<td height="63" style="height:63px;width:263px;">Bruker AVANCE III 400 MHz Superconducting Fourier</td>
			<td style="width:311px;">Bruker</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
		<tr height="42">
			<td height="42" style="height:42px;width:263px;">High-performance liquid chromatography</td>
			<td style="width:311px;">Shimadzu</td>
			<td style="width:119px;"></td>
			<td></td>
		</tr>
	</tbody>
</table>

chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes based on the oxidative iodination of terminal alkynes

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and 1-methyl-4-(1,2,2-triiodovinyl)benzene as representative examples for the practical chemoselective preparation of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes from the chemoselective iodination of terminal alkynes mediated by hypervalent-iodine reagents. The chemoselectivity was confirmed by using p-tolylethyne as a model substrate to screen a variety of iodine sources and/or the hypervalent-iodine reagents. A combination of tetrabutylammonium iodide (TBAI) and (diacetoxyiodo)benzene (PIDA) selectively generates 1-iodoalkynes, while a combination of KI and PIDA generates 1,2-diiodoalkenes. A one-pot synthesis based on both TBAI-PIDA and KI-PIDA yields the corresponding 1,1,2-triiodoalkenes. These protocols were subsequently applied to the synthesis of synthetically important aromatic and aliphatic 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes, which were obtained in good yield with excellent chemoselectivity.

The chemoselective synthesis of 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes based on the oxidative iodination of p-tolylethyne is summarized in Figure 1. All reactions were exposed to air. All compounds in this study were characterized by 1H and 13C NMR spectroscopy, mass spectrometry, and HPLC to access the structure of the product and the selectivity of the reaction, as well as to explore the purity. The obtained products are stable upon storage at 4 &#176;C in a refrigerator for four months, i.e., significant changes in HPLC and 1H NMR data were not detected. Key data for representative compounds are described in this section.
The structure of 1-(iodoethynyl)-4-methylbenzene (2, 1-iodoalkynes) was determined by comparing its NMR data with reference data. 1H NMR (400 MHz, CDCl3): &#948; = 7.32 (d, J = 8.0 Hz, 2 H), 7.11 (d, J = 8.0 Hz, 2 H), 2.34 (s, 3 H); 13C NMR (100 MHz, CDCl3): &#948; = 139.1, 132.2, 129.0, 120.4, 94.3, 21.6, 5.1. The key proton signal for the terminal alkyne (3.0 ppm) disappears and the observation of a signal at 5.1 ppm in the 13C NMR spectrum confirms the mono-iodination of p-tolylethyne (Figure 2), consistent with reported NMR data43. HPLC analysis: C18 (5 &#181;m, 4.6 mm &#215; 150 mm), CH3CN/H2O = 75/25 (v/v), flow rate = 1.0 mL/min&#8722;1, &#955; = 254 nm, retention time: 6.2 min (Figure 7).
The structure of (E)-1-(1,2-diiodovinyl)-4-methylbenzene (3, 1,2-diiodoalkenes) was determined by comparing its NMR data with reference data. 1H NMR (400 MHz, CDCl3): &#948; = 7.26 (d, J = 8.0 Hz, 2 H), 7.22 (s, 1 H), 7.15 (d, J = 8.0 Hz, 2 H), 2.34 (s, 3 H); 13C NMR (100 MHz, CDCl3): &#948; = 140.2, 139.0, 129.0, 128.4, 96.6, 80.1, 21.4. The key proton signal in the olefin at 7.2 ppm confirms the di-iodination of p-tolylethyne, and 13C NMR spectrum shows the corresponding olefin carbon atoms at 96.6 ppm and 80.1 ppm, respectively (Figure 3). The NMR data are consistent with previously reported values, in which 3 was determined as the E type18. HPLC analysis: C18 (5 &#181;m, 4.6 mm &#215; 150 mm), CH3CN/H2O = 75/25 (v/v), flow rate = 1.0 mL/min&#8722;1, &#955; = 254 nm, retention time: 10.6 min (Figure 8).
The structure of 1-methyl-4-(1,2,2-triiodovinyl)benzene (4, 1,1,2-triiodoalkene) was determined by NMR, high-resolution mass spectrometry (HRMS), and HPLC. 1H NMR (400 MHz, CDCl3): &#948; = 7.16 (s, 4 H), 2.34 (s, 3 H); 13C NMR (100 MHz, CDCl3): &#948; = 144.9, 138.9, 129.3, 127.4, 112.9, 22.2, 21.5 (Figure 4); HRMS (EI) calcd for C9H7I3: 495.7682 ([M]+); found: 495.7672 (Figure 5); HPLC analysis: C18 (5 &#181;m, 4.6 mm &#215; 150 mm), CH3CN/H2O = 75/25 (v/v), flow rate = 1.0 mL/min&#8722;1, &#955; = 254 nm, retention time: 11.5 min (Figure 9).
The chemoselectivity of the iodination was determined by HPLC. The HPLC performance of 2, 3, and 4 as external standards is shown in Figure 6. The molar ratio of 2, 3, and 4 as external standards is 39.58 : 52.14 : 22.38. The peak area ratio (%) in the HPLC chromatogram of 2:3:4 is 49.801% : 30.762% : 19.436% (Figure 6). Accordingly, the ratio of molar absorptivity is &#949;2: &#949;3: &#949;4= 2.131 : 1 : 1.472.
The TBAI-PIDA system selectively affords 2 (2:3:4= 100:0:0; Figure 7), while the KI-PIDA system selectively furnishes 3(2:3:4= 0.8:98.8:0.4; Figure 8). Combined in one-pot, the TBAI-PIDA and KI-PIDA systems efficiently yield 4&#160;as a major product (2:3:4= 3.7:3.2:93.1; Figure 9).
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/58063/58063fig1.jpg" /> 
Figure 1. Chemoselective mono-, di- and tri-iodination of alkynes. p-Tolylethyne was used as a model substrate. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58063/58063fig1large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/58063/58063fig2.jpg" /> 
Figure 2. 1H NMR and 13C NMR spectra of 2. This figure has been reproduced from ref. 36 with permission. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58063/58063fig2large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/58063/58063fig3.jpg" /> 
Figure 3. 1H NMR and 13C NMR spectra of 3. This figure has been reproduced from ref. 36 with permission. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58063/58063fig3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/58063/58063fig4.jpg" /> 
Figure 4. 1H NMR and 13C NMR spectra of 4. This figure has been reproduced from ref. 36 with permission. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58063/58063fig4large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/58063/58063fig5.jpg" /> 
Figure 5. HRMS spectra of 4. This figure has been reproduced from ref. 36 with permission. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58063/58063fig5large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 6" class="xfigimg" src="/files/ftp_upload/58063/58063fig6.jpg" /> 
Figure 6. HPLC spectrum of a mixture of 2, 3, and 4 mixture as external standards (2: 9.58 mg; 3: 19.29 mg; 4: 11.10 mg). This figure has been reproduced from ref. 36 with permission. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58063/58063fig6large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 7" class="xfigimg" src="/files/ftp_upload/58063/58063fig7.jpg" /> 
Figure 7. HPLC spectrum of 2, synthesized using the TBAI-PIDA system. This figure has been reproduced from ref. 36 with permission. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58063/58063fig7large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 8" class="xfigimg" src="/files/ftp_upload/58063/58063fig8.jpg" /> 
Figure 8. HPLC spectrum of 3, synthesized using the KI-PIDA system. This figure has been reproduced from ref. 36 with permission. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58063/58063fig8large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
<img alt="Figure 9" class="xfigimg" src="/files/ftp_upload/58063/58063fig9.jpg" /> 
Figure 9. HPLC spectrum of 3, synthesized using a combination of the TBAI-PIDA and KI-PIDA systems in one pot. This figure has been reproduced from ref. 36 with permission. <a href="https://www-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/58063/58063fig9large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes at JoVE.com

Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

Herein, detailed protocols for the oxidative iodination of terminal alkynes using hypervalent-iodine reagents are presented, which chemoselectively afford 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

We present the chemoselective synthesis of 1-(iodoethynyl)-4-methylbenzene, 1-(1,2-diiodovinyl)-4-methylbenzene, and ...

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Alkynes

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7.6K Views.  Guangdong University of Technology. Herein, detailed protocols for the oxidative iodination of terminal alkynes using hypervalent-iodine reagents are presented, which chemoselectively afford 1-iodoalkynes, 1,2-diiodoalkenes, and 1,1,2-triiodoalkenes.

Video: Chemoselective Preparation of 1-Iodoalkynes, 1,2-Diiodoalkenes, and 1,1,2-Triiodoalkenes Based on the Oxidative Iodination of Terminal Alkynes

Methods to Identify the NMR Resonances of the 13C-Dimethyl N-terminal Amine on Reductively Methylated Proteins

Nuclear magnetic resonance (NMR) spectroscopy is a proven technique for protein structure and dynamic studies. To study proteins with NMR, stable magnetic isotopes are typically incorporated metabolically to improve the sensitivity and allow for sequential resonance assignment. Reductive 13C-methylation is an alternative labeling method for proteins that are not amenable to bacterial host over-expression, the most common method of isotope incorporation. Reductive 13C-methylation is a chemical reaction performed under mild conditions that modifies a protein&#39;s primary amino groups (lysine &#949;-amino groups and the N-terminal &#945;-amino group) to 13C-dimethylamino groups. The structure and function of most proteins are not altered by the modification, making it a viable alternative to metabolic labeling. Because reductive 13C-methylation adds sparse, isotopic labels, traditional methods of assigning the NMR signals are not applicable. An alternative assignment method using mass spectrometry (MS) to aid in the assignment of protein 13C-dimethylamine NMR signals has been developed. The method relies on partial and different amounts of 13C-labeling at each primary amino group. One limitation of the method arises when the protein&#39;s N-terminal residue is a lysine because the &#945;- and &#949;-dimethylamino groups of Lys1 cannot be individually measured with MS. To circumvent this limitation, two methods are described to identify the NMR resonance of the 13C-dimethylamines associated with both the N-terminal &#945;-amine and the side chain &#949;-amine. The NMR signals of the N-terminal &#945;-dimethylamine and the side chain &#949;-dimethylamine of hen egg white lysozyme, Lys1, are identified in 1H-13C heteronuclear single-quantum coherence spectra.

Methods to Identify the NMR Resonances of the 13C-Dimethyl N-terminal Amine on Reductively Methylated Proteins

Two methods for assigning the &#945;- and &#949;-dimethylamine nuclear magnetic resonance signals of a reductively 13C-methylated N-terminal lysine are described. One method utilizes the pH-induced selectivity of the reductive methylation reaction, and the other uses aminopeptidase to selectively remove the N-terminal lysine.

Nuclear magnetic resonance (NMR) spectroscopy is a proven technique for protein structure and dynamic studies. To study proteins with NMR, stable magnetic ...

Determining the Ice-binding Planes of Antifreeze Proteins by Fluorescence-based Ice Plane Affinity

Antifreeze proteins (AFPs) are expressed in a variety of cold-hardy organisms to prevent or slow internal ice growth. AFPs bind to specific planes of ice through their ice-binding surfaces. Fluorescence-based ice plane affinity (FIPA) analysis is a modified technique used to determine the ice planes to which the AFPs bind. FIPA is based on the original ice-etching method for determining AFP-bound ice-planes. It produces clearer images in a shortened experimental time. In FIPA analysis, AFPs are fluorescently labeled with a chimeric tag or a covalent dye then slowly incorporated into a macroscopic single ice crystal, which has been preformed into a hemisphere and oriented to determine the a- and c-axes. The AFP-bound ice hemisphere is imaged under UV light to visualize AFP-bound planes using filters to block out nonspecific light. Fluorescent labeling of the AFPs allows real-time monitoring of AFP adsorption into ice. The labels have been found not to influence the planes to which AFPs bind. FIPA analysis also introduces the option to bind more than one differently tagged AFP on the same single ice crystal to help differentiate their binding planes. These applications of FIPA are helping to advance our understanding of how AFPs bind to ice to halt its growth and why many AFP-producing organisms express multiple AFP isoforms.

Antifreeze proteins (AFPs) bind to specific planes of ice to prevent or slow ice growth. Fluorescence-based ice plane affinity (FIPA) analysis is a modification of the original ice-etching method for determination of AFP-bound ice planes. AFPs are fluorescently labeled, incorporated into macroscopic single ice crystals, and visualized under UV light.

Antifreeze proteins (AFPs) are expressed in a variety of cold-hardy organisms to prevent or slow internal ice growth. AFPs bind to specific planes of ice ...

Preparation and Use of Carbonyl-decorated Carbenes in the Activation of White Phosphorus

Here we present a protocol for the synthesis of two distinct carbonyl-decorated carbenes. Both carbenes can be prepared using nearly identical procedures in multi-gram scale quantities. The goal of this manuscript is to clearly detail how to handle and prepare these unique carbenes such that a synthetic chemist of any skill level can work with them. The two carbenes described are a diamidocarbene (DAC, carbene 1) and a monoamidoaminocarbene (MAAC 2). These carbenes are highly electron-deficient and as such display reactivity profiles that are atypical of more traditional N-heterocyclic carbenes. Additionally, these two carbenes only differ in their electrophilic character and not their steric parameters, making them ideal for studying how carbene electronics influence reactivity. To demonstrate this phenomenon, we are also describing the activation of white phosphorus (P4) using these carbenes. Depending on the carbene used, two very different phosphorus-containing compounds can be isolated. When the DAC 1 is used, a tris(phosphaalkenyl)phosphane can be isolated as the exclusive product. Remarkably however, when MAAC 2 is added to P4 under identical reaction conditions, an unexpected carbene-supported P8&#160;allotrope of phosphorus is isolated exclusively. Mechanistic studies demonstrate that this carbene-supported P8allotrope forms via a [2+2] cycloaddition dimerization of a transient diphosphene which has been trapped by treatment with 2,3-dimethyl-1,3-butadiene.

Here, we present a protocol for the synthesis of two carbonyl-decorated carbenes. The protocol makes these interesting compounds readily available to chemists of all skill levels. In addition to the synthesis of these two carbenes, their use in the activation of white phosphorus is also described.

Here we present a protocol for the synthesis of two distinct carbonyl-decorated carbenes. Both carbenes can be prepared using nearly identical procedures ...

Preparation of Highly Porous Coordination Polymer Coatings on Macroporous Polymer Monoliths for Enhanced Enrichment of Phosphopeptides

We describe a protocol for the preparation of hybrid materials based on highly porous coordination polymer coatings on the internal surface of macroporous polymer monoliths. The developed approach is based on the preparation of a macroporous polymer containing carboxylic acid functional groups and the subsequent step-by-step solution-based controlled growth of a layer of a porous coordination polymer on the surface of the pores of the polymer monolith. The prepared metal-organic polymer hybrid has a high specific micropore surface area. The amount of iron(III) sites is enhanced through metal-organic coordination on the surface of the pores of the functional polymer support. The increase of metal sites is related to the number of iterations of the coating process.
The developed preparation scheme is easily adapted to a capillary column format. The functional porous polymer is prepared as a self-contained single-block porous monolith within the capillary, yielding a flow-through separation device with excellent flow permeability and modest back-pressure. The metal-organic polymer hybrid column showed excellent performance for the enrichment of phosphopeptides from digested proteins and their subsequent detection using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. The presented experimental protocol is highly versatile, and can be easily implemented to different organic polymer supports and coatings with a plethora of porous coordination polymers and metal-organic frameworks for multiple purification and/or separation applications.

A procedure for the preparation of porous hybrid separation media composed of a macroporous polymer monolith internally coated by a high surface area microporous coordination polymer is presented.

We describe a protocol for the preparation of hybrid materials based on highly porous coordination polymer coatings on the internal surface of macroporous ...

Preparation of Macroporous Epitaxial Quartz Films on Silicon by Chemical Solution Deposition

This work describes the detailed protocol for preparing piezoelectric macroporous epitaxial quartz films on silicon(100) substrates. This is a three-step process based on the preparation of a sol in a one-pot synthesis which is followed by the deposition of a gel film on Si(100) substrates by evaporation induced self-assembly using the dip-coating technique and ends with a thermal treatment of the material to induce the gel crystallization and the growth of the quartz film. The formation of a silica gel is based on the reaction of a tetraethyl orthosilicate and water, catalyzed by HCl, in ethanol. However, the solution contains two additional components that are essential for preparing mesoporous epitaxial quartz films from these silica gels dip-coated on Si. Alkaline earth ions, like Sr2+ act as glass melting agents that facilitate the crystallization of silica and in combination with cetyl trimethylammonium bromide (CTAB) amphiphilic template form a phase separation responsible of the macroporosity of the films. The good matching between the quartz and silicon cell parameters is also essential in the stabilization of quartz over other SiO2 polymorphs and is at the origin of the epitaxial growth.

A protocol is presented for the preparation of piezoelectric macroporous epitaxial films of quartz on silicon by solution chemistry using dip-coating and thermal treatments in air.

This work describes the detailed protocol for preparing piezoelectric macroporous epitaxial quartz films on silicon(100) substrates. This is a three-step ...

Photochemical Oxidative Growth of Iridium Oxide Nanoparticles on CdSe@CdS Nanorods

We demonstrate a procedure for the photochemical oxidative growth of iridium oxide catalysts on the surface of seeded cadmium selenide-cadmium sulfide (CdSe@CdS) nanorod photocatalysts. Seeded rods are grown using a colloidal hot-injection method and then moved to an aqueous medium by ligand exchange. CdSe@CdS nanorods, an iridium precursor and other salts are mixed and illuminated. The deposition process is initiated by absorption of photons by the semiconductor particle, which results with formation of charge carriers that are used to promote redox reactions. To insure photochemical oxidative growth we used an electron scavenger. The photogenerated holes oxidize the iridium precursor, apparently in a mediated oxidative pathway. This results in the growth of high quality crystalline iridium oxide particles, ranging from 0.5 nm to about 3 nm, along the surface of the rod. Iridium oxide grown on CdSe@CdS heterostructures was studied by a variety of characterization methods, in order to evaluate its characteristics and quality. We explored means for control over particle size, crystallinity, deposition location on the CdS rod, and composition. Illumination time and excitation wavelength were found to be key parameters for such control. The influence of different growth conditions and the characterization of these heterostructures are described alongside a detailed description of their synthesis. Of significance is the fact that the addition of iridium oxide afforded the rods astounding photochemical stability under prolonged illumination in pure water (alleviating the requirement for hole scavengers).

A protocol for the photochemical oxidative growth of small crystalline iridium oxide nanoparticles on the surface of CdSe@CdS seeded rod nanoparticles is presented.

We demonstrate a procedure for the photochemical oxidative growth of iridium oxide catalysts on the surface of seeded cadmium selenide-cadmium sulfide ...

Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging

Paramagnetic complexes of gadolinium(III) with acyclic or macrocyclic chelates are the most commonly used contrast agents (CAs) for magnetic resonance imaging (MRI). Their purpose is to enhance the relaxation rate of water protons in tissue, thus increasing the MR image contrast and the specificity of the MRI measurements. Current clinically approved contrast agents are low molecular weight molecules that are rapidly cleared from the body. The use of dendrimers as carriers of paramagnetic chelators can play an important role in the future development of more efficient MRI contrast agents. Specifically, the increase in local concentration of the paramagnetic species results in a higher signal contrast. Furthermore, this CA provides a longer tissue retention time due to its high molecular weight and size. Here, we demonstrate a convenient procedure for the preparation of macromolecular MRI contrast agents based on poly(amidoamine) (PAMAM) dendrimers with monomacrocyclic DOTA-type chelators (DOTA &#8211; 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetate). The chelating unit was appended by exploiting the reactivity of the isothiocyanate (NCS) group towards the amine surface groups of the PAMAM dendrimer to form thiourea bridges. Dendrimeric products were purified and analyzed by means of nuclear magnetic resonance spectroscopy, mass spectrometry, and elemental analysis. Finally, high resolution MR images were recorded and the signal contrasts obtained from the prepared dendrimeric and the commercially available monomeric agents were compared.

Preparation and In Vitro Characterization of Dendrimer-based Contrast Agents for Magnetic Resonance Imaging

This protocol describes the preparation and characterization of a dendrimeric magnetic resonance imaging (MRI) contrast agent that carries cyclen-based macrocyclic chelates coordinating paramagnetic gadolinium ions. In a series of MRI experiments in vitro, this agent produced an amplified MRI signal when compared to the commercially available monomeric analogue.

Paramagnetic complexes of gadolinium(III) with acyclic or macrocyclic chelates are the most commonly used contrast agents (CAs) for magnetic resonance ...

Preparation of Chitosan-based Injectable Hydrogels and Its Application in 3D Cell Culture

The protocol presents a facile, efficient, and versatile method to prepare chitosan-based hydrogels using dynamic imine chemistry. The hydrogel is prepared by mixing solutions of glycol chitosan with a synthesized benzaldehyde terminated polymer gelator, and hydrogels are efficiently obtained in several minutes at room temperature. By varying ratios between glycol chitosan, polymer gelator, and water contents, versatile hydrogels with different gelation times and stiffness are obtained. When damaged, the hydrogel can recover its appearances and modulus, due to the reversibility of the dynamic imine bonds as crosslinkages. This self-healable property enables the hydrogel to be injectable since it can be self-healed from squeezed pieces to an integral bulk hydrogel after the injection process. The hydrogel is also multi-responsive to many bio-active stimuli due to different equilibration statuses of the dynamic imine bonds. This hydrogel was confirmed as bio-compatible, and L929 mouse fibroblast cells were embedded following standard procedures and the cell proliferation was easily assessed by a 3D cell cultivation process. The hydrogel can offer an adjustable platform for different research where a physiological mimic of a 3D environment for cells is profited. Along with its multi-responsive, self-healable, and injectable properties, the hydrogels can potentially be applied as multiple carriers for drugs and cells in future bio-medical applications.

Here we describe a facile preparation of chitosan-based injectable hydrogels using dynamic imine chemistry. Methods to adjust the hydrogel&#8217;s mechanical strength and its application in 3D cell culture are presented.

The protocol presents a facile, efficient, and versatile method to prepare chitosan-based hydrogels using dynamic imine chemistry. The hydrogel is ...

Scale-up Chemical Synthesis of Thermally-activated Delayed Fluorescence Emitters Based on the Dibenzothiophene-S,S-Dioxide Core

We report a procedure to linearly scale-up the synthesis of 2,8-bis(3,6-di-tert-butyl-9H-carbazol-9-yl)dibenzothiophene-S,S-dioxide (compound 4) and 2,8-bis(10H-phenothiazin-10-yl)dibenzothiophene-S,S-dioxide (compound 5) using Buchwald-Hartwig cross-coupling reaction conditions. In addition, we demonstrate a scaled-up synthesis of all non-commercially available starting materials that are required for the amination cross-coupling reaction. In the present article, we provide the detailed synthetic procedures for all of the described compounds, alongside their spectral characterization. This work shows the possibility to produce organic molecules for optoelectronic applications on a large scale, which facilitates their implementation into real world devices.

Scale-up synthesis of highly efficient thermally activated delayed fluorescence emitters is described in the presented article.

We report a procedure to linearly scale-up the synthesis of 2,8-bis(3,6-di-tert-butyl-9H-carbazol-9-yl)dibenzothiophene-S,S-dioxide (compound 4) and ...

Preparation of Polyoxometalate-based Photo-responsive Membranes for the Photo-activation of Manganese Oxide Catalysts

This paper presents a method to prepare charge-transfer chromophores using polyoxotungstate (PW12O403-), transition metal ions (Ce3+ or Co2+), and organic polymers, with the aim of photo-activating oxygen-evolving manganese oxide catalysts, which are important components in artificial photosynthesis. The cross-linking technique was applied to obtain a self-standing membrane with a high PW12O403- content. Incorporation and structure retention of PW12O403- within the polymer matrix were confirmed by FT-IR and micro-Raman spectroscopy, and optical characteristics were investigated by UV-Vis spectroscopy, which revealed successful construction of the metal-to-metal charge transfer (MMCT) unit. After deposition of MnOx oxygen evolving catalysts, photocurrent measurements under visible light irradiation verified the sequential charge transfer, Mn &#8594; MMCT unit &#8594; electrode, and&#160;the photocurrent intensity was consistent with the redox potential of the donor metal (Ce or Co). This method provides a new strategy for preparing integrated systems involving catalysts and photon-absorption parts for use with photo-functional materials.

Here, we present a protocol to prepare charge transfer chromophores based on a polyoxometalate/polymer composite membrane.

This paper presents a method to prepare charge-transfer chromophores using polyoxotungstate (PW12O403-), transition metal ions (Ce3+ or Co2+), and organic ...