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

Summary

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.

Abstract

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.

Introduction

Iodoalkynes and iodoalkenes are widely used important precursors and building blocks in organic synthesis^1,2,3,4, biologically active substances, and useful in the synthesis of materials and complex molecules given the ease of converting the C-I bond^5,6,7,8. In recent years, the oxidative iodination of terminal alkynes has attracted more attention to the synthesis of iodoalkyne and iodoalkene derivatives. So far, e....

Protocol

1. Synthesis of 1-(Iodoethynyl)-4-Methylbenzene (2, 1-Iodoalkynes)

1. 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 μL (0.3 mmol) of p-tolylethyne to the mixture using a microsyringe.
2. 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.
3. Stir the reaction mixture at room temperature for 3 h.......

Discussion

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 (

Materials

Name	Company	Catalog Number	Comments
4-ethynyltoluene,98%	Energy Chemical	D080006
phenylacetylene,98%	Energy Chemical	W330041
1-ethynyl-4-methoxybenzene,98%	Energy Chemical	D080007
1-ethynyl-4-fluorobenzene,98%	Energy Chemical	D080005
4-(Trifluoromethyl)phenylacetylene,98%	Energy Chemical	W320273
4-Ethynylbenzoic acid methyl ester,97%	Energy Chemical	A020720
3-Aminophenylacetylene,97%	Energy Chemical	D080001
3-Butyn-1-ol,98%	Energy Chemical	A040031
Propargylacetate,98%	Energy Chemical	L10031
Tetrabutylammonium Iodide,98%	Energy Chemical	E010070
Potassium iodide,98%	Energy Chemical	E010364
(diacetoxyiodo)benzene,99%	Energy Chemical	A020180
acetonitrile, HPLC grade	fischer	A998-4
magnetic stirrer	IKA
rotary evaporator	Buchi
Bruker AVANCE III 400 MHz Superconducting Fourier	Bruker
High-performance liquid chromatography	Shimadzu