The authors would like to acknowledge Vanderbilt University and the Institute of Chemical Biology for financial support. Mr. Berkley Ellis and Prof. John McLean are acknowledged for High-Resolution Mass Spectral Analysis. 
&#160;

1. Representative Microwave-Assisted Denitration
<ol>
	<li>Place the azido nitrate ester (1.0 equiv., 0.2 mmol) in an 8 mL microwave reaction vial. The scale of the reaction can be increased to several mmol without any adverse effect on reaction progress.</li>
	<li>Dissolve the azido-nitrate ester in 20% aq. acetone (0.1 M, 2.0 mL). Add pyridine (5.0 equiv., 0.08 mL, 1.0 mmol) to the reaction vessel. Cap the microwave irradiation vial and place the reaction vessel in a microwave reactor cavity.</li>
	<li>Irradiate the solution at 120 &#176;C for 15 min with stirring and with a fixed hold time. The hold time represents how long the irradiation will occur at the designated temperature and resultant pressure. Heat all reactions to the reported temperature over a 2-minute ramping period. Monitor the temperature by a builtin IR sensor.</li>
	<li>After 15 min, analyze the reaction mixture using thin layer chromatography (TLC) to confirm consumption of the starting material. Use 1:1 ethyl acetate/hexanes as the eluent.
	<ol>
		<li>Visualize the TLC plate using ceric ammonium molybate stain. The Rf of the reactant and product will vary, but the reducing alcohol is generally 0.05 to 0.1 lower Rf than the reactant.</li>
	</ol>
	</li>
</ol>
2. Formation of the trichloroacetimidate
<ol>
	<li>Following complete consumption of the starting material, evaporate the solvent to a reduced volume using an airline. Then, dilute with (dichloromethane) CH2Cl2 (1.0 mL) and use a syringe to remove the water layer. Once the water layer is removed, cool the reaction mixture to 0 &#176;C using an ice-water bath.</li>
	<li>Next, add DBU (10 eq, 0.3 mL, 1.9 mmol) and 2,2,2-trichloroacetonitrile (50 eq, 1.0 mL, 10 mmol) to the reaction vessel. Both reagents are added in excess and a minimum of 1 equivalent of base and 1 equivalent of 2,2,2-trichloroacetonitrile are needed.</li>
	<li>Allow the reaction mixture to stir while warming to ambient temperature. Monitor the reaction by TLC to confirm consumption of the starting material.
	<ol>
		<li>Use 1:1 ethyl acetate/hexanes as the eluent. Visualize the TLC plate using ceric ammonium molybate stain. The Rf of the reactant and product will vary.</li>
	</ol>
	</li>
	<li>After complete consumption of starting material, transfer the reaction mixture to a recovery flask and concentrate the mixture in vacuo at 30 &#176;C. Evaporation of solvent will provide a crude pale yellow to brown oil.</li>
	<li>Purify the crude product by silica gel column chromatography with a 1.5 cm chromatography column and 1:4 ethyl acetate/hexanes as eluent. The physical form of the imidate will vary from molecule to molecule.</li>
</ol>
<img alt="Figure 1" class="xfigimg" src="/files/ftp_upload/56610/56610fig1v3.jpg" /> 
Figure 1. Representative examples of the one-pot conversion of 2-azido-1-nitrate esters to 2-azido-1-trichloroimidates. <a href="//cloudfront-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56610/56610fig1v3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

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	<li>Nicolaou, K. C., Mitchell, H. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Adventures+in+Carbohydrate+Chemistry:+New+Synthetic+Technologies,+Chemical+Synthesis,+Molecular+Design,+and+Chemical+Biology+A+list+of+abbreviations+can+be+found+at+the+end+of+this+article.+Telemachos+Charalambous+was+an+inspiring+teacher+at+the+Pancyprian+Gymnasium,+Nicosia,+Cyprus.">Adventures in Carbohydrate Chemistry: New Synthetic Technologies, Chemical Synthesis, Molecular Design, and Chemical Biology A list of abbreviations can be found at the end of this article. Telemachos Charalambous was an inspiring teacher at the Pancyprian Gymnasium, Nicosia, Cyprus.</a> Angew. Chem. Int. Ed. Engl. 40 (9), 1576-1624 (2001).</li><li>Danishefsky, S. J., Allen, J. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=From+the+laboratory+to+the+clinic:+A+retrospective+on+fully+synthetic+carbohydrate-based+anticancer+vaccines.">From the laboratory to the clinic: A retrospective on fully synthetic carbohydrate-based anticancer vaccines.</a> Angew. Chem. Int. Ed. Engl. 39 (5), 836-863 (2000).</li><li>Nicolaou, K. C., Hale, C. R. H., Nilewski, C., Ioannidou, H. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Constructing+molecular+complexity+and+diversity:+total+synthesis+of+natural+products+of+biological+and+medicinal+importance.">Constructing molecular complexity and diversity: total synthesis of natural products of biological and medicinal importance.</a> Chemical Society Reviews. 41 (15), 5185-5238 (2012).</li><li>Zhu, X., Schmidt, R. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=New+principles+for+glycoside-bond+formation.">New principles for glycoside-bond formation.</a> Angew. Chem. Int. Ed. Engl. 48 (11), 1900-1934 (2009).</li><li>Danishefsky, S. J., Bilodeau, M. T. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glycals+in+organic+synthesis:+The+evolution+of+comprehensive+strategies+for+the+assembly+of+oligosaccharides+and+glycoconjugates+of+biological+consequence.">Glycals in organic synthesis: The evolution of comprehensive strategies for the assembly of oligosaccharides and glycoconjugates of biological consequence.</a> Angew. Chem. Int. Ed. Engl. 35 (13-14), 1380-1419 (1996).</li><li>Bongat, A. F., Demchenko, A. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+trends+in+the+synthesis+of+O-glycosides+of+2-amino-2-deoxysugars.">Recent trends in the synthesis of O-glycosides of 2-amino-2-deoxysugars.</a> Carbohydr. Res. 342 (3-4), 374-406 (2007).</li><li>Feizi, T., Fazio, F., Chai, W. C., Wong, C. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Carbohydrate+microarrays+-+a+new+set+of+technologies+at+the+frontiers+of+glycomics.">Carbohydrate microarrays - a new set of technologies at the frontiers of glycomics.</a> Curr. Opin. Struct. Biol. 13 (5), 637-645 (2003).</li><li>Palmacci, E. R., Plante, O. J., Seeberger, P. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Oligosaccharide+synthesis+in+solution+and+on+solid+support+with+glycosyl+phosphates.">Oligosaccharide synthesis in solution and on solid support with glycosyl phosphates.</a> Eur. J. Org. Chem. (4), 595-606 (2002).</li><li>Stallforth, P., Lepenies, B., Adibekian, A., Seeberger, P. H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=2009+Claude+S.+Hudson+Award+in+Carbohydrate+Chemistry.+Carbohydrates:+a+frontier+in+medicinal+chemistry.">2009 Claude S. Hudson Award in Carbohydrate Chemistry. Carbohydrates: a frontier in medicinal chemistry.</a> J. Med. Chem. 52 (18), 5561-5577 (2009).</li><li>Danishefsky, S. J., Mcclure, K. F., Randolph, J. T., Ruggeri, R. B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+Strategy+for+the+Solid-Phase+Synthesis+of+Oligosaccharides.">A Strategy for the Solid-Phase Synthesis of Oligosaccharides.</a> Science. 260 (5112), 1307-1309 (1993).</li><li>Demchenko, A. V. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Stereoselective+chemical+1,2-cis+O-glycosylation:+From+'sugar+ray'+to+modern+techniques+of+the+21st+century.">Stereoselective chemical 1,2-cis O-glycosylation: From 'sugar ray' to modern techniques of the 21st century.</a> Synlett. (9), 1225-1240 (2003).</li><li>Fraserreid, B., Wu, Z. F., Udodong, U. E., Ottosson, H. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Armed-Disarmed+Effects+in+Glycosyl+Donors+-+Rationalization+and+Sidetracking.">Armed-Disarmed Effects in Glycosyl Donors - Rationalization and Sidetracking.</a> J. Org. Chem. 55 (25), 6068-6070 (1990).</li><li>Bohe, L., Crich, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=A+propos+of+glycosyl+cations+and+the+mechanism+of+chemical+glycosylation;+the+current+state+of+the+art.">A propos of glycosyl cations and the mechanism of chemical glycosylation; the current state of the art.</a> Carbohydr. Res. 403, 48-59 (2015).</li><li>Toshima, K., Tatsuta, K. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recent+Progress+in+O-Glycosylation+Methods+and+Its+Application+to+Natural-Products+Synthesis.">Recent Progress in O-Glycosylation Methods and Its Application to Natural-Products Synthesis.</a> Chem. Rev. 93 (4), 1503-1531 (1993).</li><li>Koenigs, W., Knorr, E. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Ueber+einige+Derivate+des+Traubenzuckers+und+der+Galactose.">Ueber einige Derivate des Traubenzuckers und der Galactose.</a> Chem. Ber. 34 (1), 957-981 (1901).</li><li>Mukaiyama, T., Murai, Y., Shoda, S. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=An+Efficient+Method+for+Glucosylation+of+Hydroxy+Compounds+Using+Glucopyranosyl+Fluoride.">An Efficient Method for Glucosylation of Hydroxy Compounds Using Glucopyranosyl Fluoride.</a> Chem. Lett. (3), 431-432 (1981).</li><li>Meloncelli, P. J., Martin, A. D., Lowary, T. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glycosyl+iodides.+History+and+recent+advances.">Glycosyl iodides. History and recent advances.</a> Carbohydrate Research. 344 (9), 1110-1122 (2009).</li><li>Lian, G., Zhang, X., Yu, B. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Thioglycosides+in+carbohydrate+research.">Thioglycosides in carbohydrate research.</a> Carbohydr. Res. 403, 13-22 (2015).</li><li>Schmidt, R. R., Kinzy, W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Anomeric-Oxygen+Activation+for+Glycoside+Synthesis+-+the+Trichloroacetimidate+Method.">Anomeric-Oxygen Activation for Glycoside Synthesis - the Trichloroacetimidate Method.</a> Advances in Carbohydrate Chemistry and Biochemistry. 50, 21-123 (1994).</li><li>Schmidt, R. R., Toepfer, A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Glycosylation+with+highly+reactive+glycosyl+donors:+efficiency+of+the+inverse+procedure.">Glycosylation with highly reactive glycosyl donors: efficiency of the inverse procedure.</a> Tetrahedron Lett. 32 (28), 3353-3356 (1991).</li><li>Keith, D. J., Townsend, S. D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Direct,+microwave-assisted+substitution+of+anomeric+nitrate-esters.">Direct, microwave-assisted substitution of anomeric nitrate-esters.</a> Carbohydr. Res. 442, 20-24 (2017).</li><li>Bukowski, R., et al. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Synthesis+and+Conformational+Analysis+of+the+T-Antigen+Disaccharide(B-D-Gal-(1->3)-a-D-GalNAc-OMe).">Synthesis and Conformational Analysis of the T-Antigen Disaccharide(B-D-Gal-(1->3)-a-D-GalNAc-OMe).</a> Eur. J. Org. Chem. 14, 2697-2705 (2001).</li></ol>

The authors have no competing financial interests.

The protocol described in this tutorial provides a method to convert nitrate esters to useful, reactive functionality. In a broader sense, employing a microwave reactor to complete specific maneuvers over the course of a carbohydrate synthesis has the potential to make difficult transformations facile and routine. Our goal in this tutorial is to demonstrate how to handle carbohydrates in the context of microwave irradiation.
In the case of the parent reaction, previous efforts to achieve denitration have typically relied on strongly nucleophilic reagents and extended reaction times. The strength of the technology described herein is that the microwave provides high-powered heating in a very short interval, allowing for quantitative manipulation of an anomeric nitrate ester. Thus far, the method works best with compounds that are glucose configured at C2 i.e. &#34;equatorial&#34; alcohol at this position. Compounds that feature &#34;axial&#34; mannose configuration at C2 must be subjected to prolonged irradiation, as they are resistant to hydrolysis. While the reaction is conducted in the presence of base to sequester the acid produced in the de- nitration, base can be excluded for molecules that are not acid labile. Moreover, reaction times can be increased to hydrolyze molecules that are resistant to the reaction (i.e. peracetylated sugars). In regards to purification, you can purify the alcohol produced after the microwave reaction.

Due to their ubiquity in molecular biology, carbohydrates have been longstanding targets for chemical synthesis.1,2,3 At the core of any successful synthetic campaign is the correct deployment of glycosylation reactions to build the oligosaccharide chain.4,5,6,7,8,9,10,11,12 Not surprisingly, there are a large number of methods to install glycosidic bonds.13,14 The Koenigs-Knorr method is one of the earliest known procedures and involves coupling a glycosyl chloride or bromide with an alcoholic component, usually under heavy metal (mercury or silver) activation.15 Related glycosyl fluorides were first introduced as donors in 1981 by the Mukaiyama group and have found widespread application due to their increased thermal and chemical stability.16 On the opposite end of the reactivity spectrum are glycosyl iodides, which are far more reactive than the other halides. Increased reactivity is accompanied by increased stereocontrol, particularly when forming &#945;-linked oligosaccharides.17 In addition to &#34;haloglycosides&#34;, thioglycosides have found wide utility, in part, due to their ease of formation, stability to a multitude of reaction conditions, and activation with electrophilic reagents.18
The methods described above focus on converting an anomeric alcohol to a &#34;non-oxygen&#34; containing, latent leaving group that is activated and ultimately displaced by an alcohol from an acceptor molecule. Anomeric oxygen activation as described by the Schmidt school, focuses on converting the C1 oxygen itself, to a leaving group.19 This method is the most powerful and widely used in chemical glycosylation reactions. Trichloroacetimidate donors are readily prepared from a reducing sugar and trichloroacetonitrile in the presence of a base such as potassium carbonate (K2CO3) or 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). These species are then activated using Lewis acids.20
Recently, we have reported that 2-azido-1-trichloroacetimidate donors can be directly prepared from glycals. The process involves a two reaction, one-pot procedure from 2-azido-1-nitrate esters.21 This detailed protocol is intended to assist practitioners in successfully completing the transformation in high yield. Of particular interest is the first step of the sequence, which focuses on thermal denitration under microwave- assisted heating. We also hope to provide a visual tutorial on employing microwave reactors in organic synthesis.

<table>
	<tbody>
		<tr>
			<td>230 400 mesh silica gel</td>
			<td>SiliCycle Inc</td>
			<td>R10030B</td>
			<td></td>
		</tr>
		<tr>
			<td>TLC plates</td>
			<td>SiliCycle Inc</td>
			<td>TLG-R10014B-527</td>
			<td></td>
		</tr>
		<tr>
			<td>Ceric ammonium molybdate</td>
			<td>Sigma-Aldrich</td>
			<td>A1343</td>
			<td></td>
		</tr>
		<tr>
			<td>Solvent Still</td>
			<td>Mbraun</td>
			<td>MB-SPS-800</td>
			<td></td>
		</tr>
		<tr>
			<td>Infared spectrometer</td>
			<td>Thermo</td>
			<td>Thermo Electron IR100</td>
			<td></td>
		</tr>
		<tr>
			<td>Nuclear Magnetic Resonance</td>
			<td>Bruker</td>
			<td></td>
			<td>400, 600 MHz</td>
		</tr>
		<tr>
			<td>LC/MS</td>
			<td>Thermo/Dionex</td>
			<td></td>
			<td>Single quad, ESI</td>
		</tr>
		<tr>
			<td>HRMS</td>
			<td>Agilent</td>
			<td>Synapt G2 S HDMS</td>
			<td></td>
		</tr>
		<tr>
			<td>Microwave reactor</td>
			<td>Anton Parr</td>
			<td>Anton Parr G10 Monowave 200</td>
			<td></td>
		</tr>
		<tr>
			<td>DBU</td>
			<td>Sigma-Aldrich</td>
			<td>139009</td>
			<td></td>
		</tr>
		<tr>
			<td>CCl3CN</td>
			<td>Sigma-Aldrich</td>
			<td>T53805</td>
			<td></td>
		</tr>
		<tr>
			<td>Pyridine</td>
			<td>Sigma-Aldrich</td>
			<td>270970</td>
			<td></td>
		</tr>
		<tr>
			<td>Acetone</td>
			<td>Fisher Scientific</td>
			<td>A18-20</td>
			<td>Tech. grade</td>
		</tr>
		<tr>
			<td>Phase separator</td>
			<td>Biotage</td>
			<td>120-1901-A</td>
			<td></td>
		</tr>
		<tr>
			<td>Rotary evaporator</td>
			<td>Buchi</td>
			<td>R-100</td>
			<td></td>
		</tr>
	</tbody>
</table>

one-pot microwave-assisted conversion of anomeric nitrate-esters to trichloroacetimidates

The goal of the following procedure is to provide a demonstration of the one-pot conversion of a 2-azido-1-nitrate-ester to a trichloroacetimidate glycosyl donor. Following azido-nitration of a glycal, the product 2-azido-1-nitrate ester can be hydrolyzed under microwave-assisted irradiation. This transformation is usually achieved using strongly nucleophilic reagents and extended reaction times. Microwave irradiation induces hydrolysis, in the absence of reagents, with short reaction times. Following denitration, the intermediate anomeric alcohol is converted, in the same pot, to the corresponding 2-azido-1-trichloroacetimidate.

The technology described herein was demonstrated on a pool of three 2-azido-1-nitrate esters. In each case the first step of the reaction was complete within 20 minutes.
<img alt="Figure 2" class="xfigimg" src="/files/ftp_upload/56610/56610fig2v3.jpg" /> 
Figure 2. Representative example of hydrolysis (1 -&#62;2), and one-pot conversion of 2-azido-1-nitrate ester of 1 (1-&#62;3). <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56610/56610fig2v3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
(2S,3R,4S,5S,6R)-2-(((2R,3S,4R,5R,6R)-4-acetoxy-2-(acetoxymethyl)-5-azido-6-(imino(2l3-trichloran-2-yl)methoxy)tetrahydro-2H-pyran-3- yl)oxy)-6-(acetoxymethyl)tetrahydro-2H-pyran-3,4,5-triyl triacetate (3) A mixture of 11:1:6 (alpha manno-/alpha gluco-/beta gluco-) configured azidonitrate esters 1 (1.0 equiv., 0.133 g, 0.20 mmol) was dissolved in 20% aq. acetone (2.0 mL) and treated with pyridine (5.0 equiv., 1.0 mmol, 0.8 mL). The reaction was heated by microwave irradiation to 120 &#176;C for 10 min. Next, the reaction mixture was cooled to 0 &#176;C and treated with CH2Cl2 (1.0 mL). The aqueous layer of the reaction was removed. Then the reaction was added DBU (10 equiv., 0.3 mL, 1.9 mmol), and 2,2,2- trichloroacetonitrile (50 equiv., 1.0 mL, 10 mmol).15 The reaction was allowed to warm to rt. After complete consumption of the starting material, the mixture was concentrated in vacuo. The crude oil was purified by flash chromatography (10:3 - 1:1 hexanes/ EtOAc) to give a 5:1 (gluco-/ manno-) mixture of alpha imidate products 3 (0.133 g, 0.174 mmol, 87% overall). Under these reaction conditions the manno- configured starting material is more resistant to hydrolysis as previously mentioned. In this reaction, &#62;95% of the gluco- configured starting material was successfully converted to alpha imidate 3 while 62% of the manno- configured starting material was converted to imidate product. Spectroscopic data agreed with previously reported data21. As a mixture of complex C-2 isomers: 1H NMR (400 MHz, CDCl3) &#948; 8.64 (s, 1H), 6.46 (d, J = 3.6 Hz, 1H), 5.54 (m, J = 9.6 Hz), 5.33 (d, J = 3.6 Hz), 5.11 (dd, J = 10.6 Hz, J = 7.9 Hz), 5.04 (dd, J = 9.6, 3.6 Hz), 4.93 (dd, J = 10.6, 3.6 Hz, 1H ), 4.49 (d, J = 7.9 Hz, 1H), 4.48 (m, 1H ), 4.10 (m, 4H), 3.85 (m, 2H), 2.14 (s, 3H), 2.09 (s, 3H,), 2.06 (s, 3H), 2.02 (s, 6H), 1.99 (s, 3H), 1.95 (s, 3H); 13C NMR (100 MHz, CDCl3) &#948; 171.2, 170.4, 170.2, 170.1, 169.4, 169.2, 169.0, 162.1, 101.3, 92.9, 76.6, 71.2, 70.9, 70.8, 69.8, 69.5, 69.2, 66.7, 61.5, 60.8, 21.1, 21.0, 20.7, 20.6.
<img alt="Figure 3" class="xfigimg" src="/files/ftp_upload/56610/56610fig3v3.jpg" /> 
Figure 3. Representative example of hydrolysis (4 -&#62;5), and one-pot conversion of 2-azido-1-nitrate ester of 4 (4-&#62;6). <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56610/56610fig3v3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
((3aR,4R,7R,7aR)-7-azido-6-hydroxy-2,2-dimethyltetrahydro-4H-[1,3]dioxolo[4,5-c]pyran-4-yl)methyl acetate (6). Azidonitrate ester 4 (1.0 equiv., 0.150 g, 0.451 mmol) in a solution of 1:4 water/acetone (4.0 mL) and pyridine (5.0 equiv., 0.18 mL, 2.26 mmol) was heated by microwave irradiation to 110 &#176;C for 10 min. Then, the reaction was vial was concentrated under a stream of air to reduce the solvent mixture to ~1/2 its initial volume. The crude reaction mixture was added CH2Cl2 (4.0 mL). The aqueous layer of the reaction was removed. Then the reaction was added DBU (2.0 equiv., 0.14 mL, 0.90 mmol), and 2,2,2-trichloroacetonitrile (10 equiv., 0.45 mL, 4.51 mmol) at 0 &#176;C. At 30 min., the reaction was concentrated to a crude dark brown oil. The crude oil was passed through a plug of silica gel in a filter funnel and concentrated then purified by flash chromatography (2:5 EtOAc/hexanes) to give a 34:1 mixture (alpha/beta) imidate 6 (0.189 g, 0.438 mmol, &#62;95%) as a yellow oil. Spectroscopic data agreed with previously reported data21. R&#402; 0.26 (1:3 EtOAc/hexanes); [&#945;]D20 +6.63&#176; (c 0.3, CHCl3); IR (thin film, cm-1) 3943.02, 3689.98, 3053.89, 2986.53, 2684.50, 2409.92, 2304.81, 2115.20, 1735.63, 1674.77, 1616.82, 1421.56, 1265.14, 741.47, 705.37; 1H NMR (400 MHz, CDCl3): alpha anomer &#948;8.75 (s, 1H), 6.34 (d, J = 3.4 Hz, 1H), 4.48 (dd, 1H, J = 5.5, 7.9 Hz, 1H), 4.44-4.24 (m, 4H), 3.76 (dd, J = 3.4, 7.7 Hz, 1H), 2.04 (s, 3H), 1.54 (s, 3H), 1.36 (s, 3H); 13C (100 MHz, CDCl3): &#948;170.69, 160.47, 110.54, 94.34, 90.67, 73.35, 72.32, 68.13, 63.13, 60.11, 27.92, 26.00, 20.75; HRQ-TOF/MS (m/z): calcd for [M+Na]+, C13H17Cl3N4O6, 453.0111, found 453.1277.
<img alt="Figure 4" class="xfigimg" src="/files/ftp_upload/56610/56610fig4v3.jpg" /> 
Figure 4. Representative example of hydrolysis (7 -&#62;8), and one-pot conversion of 2-azido-1-nitrate ester of 7 (7-&#62;9). <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56610/56610fig4v3large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>
2R,3S,4R,5R,6R)-2-(acetoxymethyl)-5-azido-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4-diyl diacetate and (2R,3S,4R,5S,6R)-2-(acetoxymethyl)-5-azido-6-(2,2,2-trichloro-1-iminoethoxy)tetrahydro-2H-pyran-3,4-diyl diacetate (9). A 1:14.4:27.4 (beta gluco-/ alpha manno-/ alpha gluco-) mixture of triacetate 7 (1.0 equiv., 0.438 g, 1.164 mmol) in a solution of 1:4 water/acetone (10.0 mL) and pyridine (5.0 equiv., 0.47 mL, 5.82 mmol) was heated by microwave irradiation at 120 &#176;C for 20 min. Then, the reaction vial was concentrated under a stream of air to reduce the initial amount of solvent mixture to ~1/2 of its initial volume. The crude reaction mixture was added CH2Cl2&#160; (10.0 mL). The aqueous layer of the reaction was removed. Then the reaction was added DBU (1.0 equiv., 0.18 mL, 1.164 mmol), and 2,2,2-trichloroacetonitrile (10 equiv., 1.2 mL, 11.64 mmol) at 0 &#176;C. At 1 h, the reaction was a light orange and the pH of the reaction mixture was 7. Additional DBU (1.0 equiv., 0.18 mL, 1.164 mmol) was added and the reaction quickly turned its characteristic dark brown color. At 3 h, the reaction was concentrated to crude dark brown oil. The crude oil was purified by flash chromatography (2:5 EtOAc/hexanes) to give a 1:1.7 gluco-/manno- configured mixture of alpha imidate 9 (0.3758 g, 0.790 mmol, 68%) as a yellow oil. Spectroscopic data agreed with previously reported data21. 1H NMR (400 MHz, CDCl3): As a complex mixture of isomers: &#948; 8.68 (s), 6.51 (d, J = 3.7 Hz), 5.51 (m), 5.13 (m), 5.09 (dd, J = 10.3, 3.7 Hz), 4.24 (dd, J = 12.0, 3.8 Hz), 4.19-4.15 (m) 4.09 (dd, J = 12.0, 1.8 Hz), 2.02 (s), 2.00 (s), 1.98 (s), 1.97 (s); 13C NMR (100 MHz, CDCl3): &#948; 170.5, 170.0, 169.8, 169.5, 160.7, 92.9, 90.7, 70.0, 69.8, 69.7, 67.7, 61.4, 20.7, 20.6, 20.5.
<img alt="Figure 5" class="xfigimg" src="/files/ftp_upload/56610/56610fig5.jpg" /> 
Figure 5. 1H and 13C Spectra of 3. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56610/56610fig5large.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/56610/56610fig6.jpg" /> 
Figure 6. 1H and 13C Spectra of 6. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56610/56610fig6large.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/56610/56610fig7.jpg" /> 
Figure 7. 1H and 13C Spectra of 9. <a href="https://cloudflare-jove-com.remotexs.ntu.edu.sg/files/ftp_upload/56610/56610fig7large.jpg" target="_blank">Please click here to view a larger version of this figure.</a>

Watch this Scientific Journal Video about One-pot Microwave-assisted Conversion of Anomeric Nitrate-esters to Trichloroacetimidates at JoVE.com

One-pot Microwave-assisted Conversion of Anomeric Nitrate-esters to Trichloroacetimidates

A 2-azido-1-nitrate-ester can be converted to the corresponding 2-azido-1-trichloroacetimidate in a one-pot procedure. The goal of the manuscript is to demonstrate utility of the microwave reactor in carbohydrate synthesis.

The goal of the following procedure is to provide a demonstration of the one-pot conversion of a 2-azido-1-nitrate-ester to a trichloroacetimidate ...

one-pot-microwave-assisted-conversion-anomeric-nitrate-esters-to

Nanyang Technological University

Research

JoVE Journal

Chemistry

7.4K Views.  Vanderbilt University. A 2-azido-1-nitrate-ester can be converted to the corresponding 2-azido-1-trichloroacetimidate in a one-pot procedure. The goal of the manuscript is to demonstrate utility of the microwave reactor in carbohydrate synthesis.

Video: One-pot Microwave-assisted Conversion of Anomeric Nitrate-esters to Trichloroacetimidates

Microwave-assisted Intramolecular Dehydrogenative Diels-Alder Reactions for the Synthesis of Functionalized Naphthalenes/Solvatochromic Dyes

Functionalized naphthalenes have applications in a variety of research fields ranging from the synthesis of natural or biologically active molecules to the preparation of new organic dyes. Although numerous strategies have been reported to access naphthalene scaffolds, many procedures still present limitations in terms of incorporating functionality, which in turn narrows the range of available substrates. The development of versatile methods for direct access to substituted naphthalenes is therefore highly desirable.
The Diels-Alder (DA) cycloaddition reaction is a powerful and attractive method for the formation of saturated and unsaturated ring systems from readily available starting materials. A new microwave-assisted intramolecular dehydrogenative DA reaction of styrenyl derivatives described herein generates a variety of functionalized cyclopenta[b]naphthalenes that could not be prepared using existing synthetic methods. When compared to conventional heating, microwave irradiation accelerates reaction rates, enhances yields, and limits the formation of undesired byproducts.
The utility of this protocol is further demonstrated by the conversion of a DA cycloadduct into a novel solvatochromic fluorescent dye via a Buchwald-Hartwig palladium-catalyzed cross-coupling reaction. Fluorescence spectroscopy, as an informative and sensitive analytical technique, plays a key role in research fields including environmental science, medicine, pharmacology, and cellular biology. Access to a variety of new organic fluorophores provided by the microwave-assisted dehydrogenative DA reaction allows for further advancement in these fields.

Microwave-assisted intramolecular dehydrogenative Diels-Alder (DA) reactions provide concise access to functionalized cyclopenta[b]naphthalene building blocks. The utility of this methodology is demonstrated by one-step conversion of the dehydrogenative DA cycloadducts into novel solvatochromic fluorescent dyes via Buchwald-Hartwig palladium-catalyzed cross-coupling reactions.

Functionalized naphthalenes have applications in a variety of research fields ranging from the synthesis of natural or biologically active molecules to ...

Microwave-assisted Functionalization of Poly(ethylene glycol) and On-resin Peptides for Use in Chain Polymerizations and Hydrogel Formation

One of the main benefits to using poly(ethylene glycol) (PEG) macromers in hydrogel formation is synthetic versatility. The ability to draw from a large variety of PEG molecular weights and configurations (arm number, arm length, and branching pattern) affords researchers tight control over resulting hydrogel structures and properties, including Young&#8217;s modulus and mesh size. This video will illustrate a rapid, efficient, solvent-free, microwave-assisted method to methacrylate PEG precursors into poly(ethylene glycol) dimethacrylate (PEGDM). This synthetic method provides much-needed starting materials for applications in drug delivery and regenerative medicine. The demonstrated method is superior to traditional methacrylation methods as it is significantly faster and simpler, as well as more economical and environmentally friendly, using smaller amounts of reagents and solvents. We will also demonstrate an adaptation of this technique for on-resin methacrylamide functionalization of peptides. This on-resin method allows the N-terminus of peptides to be functionalized with methacrylamide groups prior to deprotection and cleavage from resin. This allows for selective addition of methacrylamide groups to the N-termini of the peptides while amino acids with reactive side groups (e.g.&#160;primary amine of lysine, primary alcohol of serine, secondary alcohols of threonine, and phenol of tyrosine) remain protected, preventing functionalization at multiple sites. This article will detail common analytical methods (proton Nuclear Magnetic Resonance spectroscopy (;H-NMR) and Matrix Assisted Laser Desorption Ionization Time of Flight mass spectrometry (MALDI-ToF)) to assess the efficiency of the functionalizations. Common pitfalls and suggested troubleshooting methods will be addressed, as will modifications of the technique which can be used to further tune macromer functionality and resulting hydrogel physical and chemical properties. Use of synthesized products for the formation of hydrogels for drug delivery and cell-material interaction studies will be demonstrated, with particular attention paid to modifying hydrogel composition to affect mesh size, controlling hydrogel stiffness and drug release.

Microwave-assisted Functionalization of Polyethylene glycol and On-resin Peptides for Use in Chain Polymerizations and Hydrogel Formation

This video will illustrate a rapid, efficient method to methacrylate poly(ethylene glycol), enabling chain polymerizations and hydrogel synthesis. It will demonstrate how to similarly introduce methacrylamide functionalities into peptides, detail common analytical methods to assess functionalization efficiency, provide suggestions for troubleshooting and advanced modifications, and demonstrate typical hydrogel characterization techniques.

One of the main benefits to using poly(ethylene glycol) (PEG) macromers in hydrogel formation is synthetic versatility. The ability to draw from a large ...

Preparation of Silica Nanoparticles Through Microwave-assisted Acid-catalysis

Microwave-assisted synthetic techniques were used to quickly and reproducibly produce silica nanoparticle sols using an acid catalyst with nanoparticle diameters ranging from 30-250 nm by varying the reaction conditions. Through the selection of a microwave compatible solvent, silicic acid precursor, catalyst, and microwave irradiation time, these microwave-assisted methods were capable of overcoming the previously reported shortcomings associated with synthesis of silica nanoparticles using microwave reactors. The siloxane precursor was hydrolyzed using the acid catalyst, HCl. Acetone, a low-tan &#948; solvent, mediates the condensation reactions and has minimal interaction with the electromagnetic field. Condensation reactions begin when the silicic acid precursor couples with the microwave radiation, leading to silica nanoparticle sol formation. The silica nanoparticles were characterized by dynamic light scattering data and scanning electron microscopy, which show the materials&#39; morphology and size to be dependent on the reaction conditions. Microwave-assisted reactions produce silica nanoparticles with roughened textured surfaces that are atypical for silica sols produced by St&#246;ber&#39;s methods, which have smooth surfaces.

Silica nanoparticles were prepared using acid-catalysis of a siloxane precursor and microwave-assisted synthetic techniques resulting in the controlled growth of nanomaterials ranging from 30-250 nm in diameter. The growth dynamics can be controlled by varying the initial silicic acid concentration, time of the reaction, and temperature of reaction.

Microwave-assisted synthetic techniques were used to quickly and reproducibly produce silica nanoparticle sols using an acid catalyst with nanoparticle ...

Preparation of N-(2-alkoxyvinyl)sulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile N-(2-alkoxyvinyl)sulfonamides, which react under a variety of conditions to afford useful N- and O-containing compounds. Acid-catalyzed addition of alcohols or thiols to N-(2-alkoxyvinyl)sulfonamide-containing phthalans provides access to ketals and thioketals, respectively. Selective reduction of the vinyl group in N-(2-alkoxyvinyl)sulfonamide-containing phthalans via hydrogenation yields the corresponding phthalan in good yield, whereas reduction with sodium bis(2-methoxyethoxy)aluminumhydride generates a ring-opened phenethylamine analogue. Because the N-(2-alkoxyvinyl)sulfonamide functional group is synthetically versatile, but often hydrolytically unstable, this protocol emphasizes key techniques in preparing, handling, and reacting these pivotal substrates in several useful transformations.

Preparation of N-2-alkoxyvinylsulfonamides from N-tosyl-1,2,3-triazoles and Subsequent Conversion to Substituted Phthalans and Phenethylamines

Representative experimental procedures for the synthesis of N-(2-alkoxyvinyl)sulfonamides and subsequent conversion to phthalan and phenethylamine derivatives are presented in detail.

Decomposition of N-tosyl-1,2,3-triazoles with rhodium(II) acetate dimer in the presence of alcohols forms synthetically versatile ...

Reducing Willow Wood Fuel Emission by Low Temperature Microwave Assisted Hydrothermal Carbonization

Biomass is a sustainable fuel, as its CO2 emissions are reintegrated in biomass growth. However, the inorganic precursors in the biomass cause a negative environmental impact and slag formation. The selected short rotation coppice (SRC) willow wood has a high ash content (<img alt="Equation 1" src="/files/ftp_upload/58970/58970eq1.jpg" /> = 1.96%) and, therefore, a high content of emission and slag precursors. Therefore, the reduction of minerals from SRC willow wood by low temperature microwave assisted hydrothermal carbonization (MAHC) at 150 &#176;C, 170 &#176;C, and 185 &#176;C is investigated. An advantage of MAHC over conventional reactors is an even temperature conductance in the reaction medium, as microwaves penetrate the whole reactor volume. This allows a better temperature control and a faster cooldown. Therefore, a succession of depolymerization, transformation and repolymerization reactions can be analyzed effectively. In this study, the analysis of the mass loss, ash content and composition, heating values and molar O/C and H/C ratios of the treated and untreated SCR willow wood showed that the mineral content of the MAHC coal was reduced and the heating value increased. The process water showed a decreasing pH and contained furfural and 5-methylfurfural. A process temperature of 170 &#176;C showed the best combination of energy input and ash component reduction. The MAHC allows a better understanding of the hydrothermal carbonization process, while a large-scale industrial application is unlikely because of the high investment costs.

A protocol for the emission precursor depletion from low quality biomass by low temperature microwave assisted hydrothermal carbonization treatment is presented. This protocol includes the microwave parameters and the analysis of the biocoal product and process water.

Biomass is a sustainable fuel, as its CO2 emissions are reintegrated in biomass growth. However, the inorganic precursors in the biomass cause a negative ...

Synthesis of In37P20(O2CR)51 Clusters and Their Conversion to InP Quantum Dots

This text presents a method for the synthesis of In37P20(O2C14H27)51 clusters and their conversion to indium phosphide quantum dots. The In37P20(O2CR)51 clusters have been observed as intermediates in the synthesis of InP quantum dots from molecular precursors (In(O2CR)3, HO2CR, and P(SiMe3)3) and may be isolated as a pure reagent for subsequent study and use as a single-source precursor. These clusters readily convert to crystalline and relatively monodisperse samples of quasi-spherical InP quantum dots when subjected to thermolysis conditions in the absence of additional precursors above 200 &#176;C. The optical properties, morphology, and structure of both the clusters and quantum dots are confirmed using UV-Vis spectroscopy, photoluminescence spectroscopy, transmission electron microscopy, and powder X-ray diffraction. The molecular symmetry of the clusters is additionally confirmed by solution-phase 31P NMR spectroscopy. This protocol demonstrates the preparation and isolation of atomically-precise InP clusters, and their reliable and scalable conversion to InP QDs.

Synthesis of In37P20O2CR51 Clusters and Their Conversion to InP Quantum Dots

A protocol for the synthesis of In37P20(O2C14H27)51 clusters and their conversion to indium phosphide quantum dots is presented.

This text presents a method for the synthesis of In37P20(O2C14H27)51 clusters and their conversion to indium phosphide quantum dots. The In37P20(O2CR)51 ...

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines

A synthetic process for the preparation of a variety of 1-aryl-1H-pyrazole-5-amines was developed. The microwave-mediated nature of this method makes it efficient in both time and resources and utilizes water as the solvent. 3-Aminocrotononitrile or an appropriate &#945;-cyanoketone is combined with an aryl hydrazine and dissolved in 1 M HCl. The mixture is then heated in a microwave reactor at 150 &#176;C, typically for 10-15 min. The product can be readily obtained by basifying the solution with 10% NaOH and isolating the desired compound with a simple vacuum filtration. The use of water as a solvent in this reaction lends to its ease and utility in production, and this method is easily reproducible with a variety of functional groups. Typical isolated yields range from 70-90%, and reactions can be performed on the milligram to gram scale with little to no change in observed yields. Some of the applications of these molecules and their derivatives include pesticides, anti-malarials, and chemotherapeutics, among many others.

Microwave-Assisted Preparation of 1-Aryl-1H-pyrazole-5-amines

1-Aryl-1H-pyrazole-5-amines are prepared from aryl hydrazines combined with either 3-aminocrotononitrile or an &#945;-cyanoketone in a 1 M HCl solution using a microwave reactor. Most reactions are done in 10-15 minutes and pure product can be obtained via vacuum filtration with typical isolated yields of 70-90%.

A synthetic process for the preparation of a variety of 1-aryl-1H-pyrazole-5-amines was developed. The microwave-mediated nature of this method makes it ...

Hierarchical and Programmable One-Pot Oligosaccharide Synthesis

This article presents a general experimental protocol for programmable one-pot oligosaccharide synthesis and demonstrates how to use Auto-CHO software for generating potential synthetic solutions. The programmable one-pot oligosaccharide synthesis approach is designed to empower fast oligosaccharide synthesis of large amounts using thioglycoside building blocks (BBLs) with the appropriate sequential order of relative reactivity values (RRVs). Auto-CHO is a cross-platform software with a graphical user interface that provides possible synthetic solutions for programmable one-pot oligosaccharide synthesis by searching a BBL library (containing about 150 validated and &#62;50,000 virtual BBLs) with accurately predicted RRVs by support vector regression. The algorithm for hierarchical one-pot synthesis has been implemented in Auto-CHO and uses fragments generated by one-pot reactions as new BBLs. In addition, Auto-CHO allows users to give feedback for virtual BBLs to keep valuable ones for further use. One-pot synthesis of stage-specific embryonic antigen 4 (SSEA-4), which is a pluripotent human embryonic stem cell marker, is demonstrated in this work.

This protocol demonstrates how to use the Auto-CHO software for hierarchical and programmable one-pot synthesis of oligosaccharides. It also describes the general procedure for RRV determination&#160;experiments and one-pot glycosylation of SSEA-4.

This article presents a general experimental protocol for programmable one-pot oligosaccharide synthesis and demonstrates how to use Auto-CHO software for ...

Versatile CO2 Transformations into Complex Products: A One-pot Two-step Strategy

CO2 transformations using a one-pot two-step method are presented herein. The purpose of the method is to give access to a variety of value-added products and notably to generate chiral carbon centers. The crucial first step consists in the selective double hydroboration of CO2 catalyzed by an iron hydride complex. The product obtained with this 4 e- reduction is a rare bis(boryl)acetal, compound 1, which is subjected in situ to three different reactions in a second step. The first reaction concerns a condensation reaction with (diisopropyl)phenylamine affording the corresponding imine 2. In the second and third reaction, intermediate 1 reacts with triazol-5-ylidene (Enders&#39; carbene) to afford compounds 3 or 4, depending on the reaction conditions. In both compounds, C-C bonds are formed, and chiral centers are generated from CO2 as the only source of carbon. Compound 4 exhibits two chiral centers obtained in a diastereoselective manner in a formose-type mechanism. We proved that the remaining boryl fragment plays a key role in this unprecedented stereocontrol. The interest of the method stands on the reactive and versatile nature of 1, giving rise to various complex molecules from a single intermediate. The complexity of a two-step method is compensated by the overall short reaction time (2 h for the larger reaction time), and mild reaction conditions (25 &#176;C to 80 &#176;C and 1 to 3 atm of CO2).

Versatile CO2 Transformations into Complex Products: A One-pot Two-step Strategy

CO2 transformations are conducted in a one-pot two-step procedure for the synthesis of complex molecules. The selective 4 e- reduction of CO2 with a hydroborane reductant affords a reactive and versatile bis(boryl)acetal intermediate which is subsequently involved in condensation reaction or carbene-mediated C-C coupling generation.

CO2 transformations using a one-pot two-step method are presented herein. The purpose of the method is to give access to a variety of value-added products ...

A Microwave-Assisted Direct Heteroarylation of Ketones Using Transition Metal Catalysis

Heteroarylation introduces heteroaryl fragments to organic molecules. Despite the numerous available reactions reported for arylation via transition metal catalysis, the literature on direct heteroarylation is scarce. The presence of heteroatoms such as nitrogen, sulfur and oxygen often make heteroarylation a challenging research field due to catalyst poisoning, product decomposition and the rest. This protocol details a highly efficient direct &#945;-C(sp3) heteroarylation of ketones under microwave irradiation. Key factors for successful heteroarylation include the use of XPhos Palladacycle Gen. 4 Catalyst, excess base to suppress side reactions and the high temperature and pressure achieved in a sealed reaction vial under microwave irradiation. The heteroarylation compounds prepared by this method were fully characterized by proton nuclear magnetic resonance spectroscopy (1H NMR), carbon nuclear magnetic resonance spectroscopy (13C NMR) and high-resolution mass spectrometry (HRMS). This methodology has several advantages over literature precedents including broad substrate scope, rapid reaction time, greener procedure and operational simplicity by eliminating the preparation of intermediates such as silyl enol ether. Possible applications for this protocol include, but are not limited to, diversity-oriented synthesis for the discovery of biologically active small molecules, domino synthesis for the preparation of natural products and ligand development for new transition metal catalytic systems.

Heteroaryl compounds are important molecules utilized in organic synthesis, medicinal and biological chemistry. A microwave-assisted heteroarylation using palladium catalysis provides a rapid and efficient method to attach heteroaryl moieties directly to ketone substrates.

Heteroarylation introduces heteroaryl fragments to organic molecules. Despite the numerous available reactions reported for arylation via transition metal ...