Pd-Catalyzed Carbonyl Insertion Coupling Reactions of a Hypervalent Iodoheterocycle with Alcohols and Amines

The palladium-catalyzed cross-coupling carbonyl insertion reaction between 3,7-bis(N,N-dimethylamino)-10H-dibenz[b,e]iodinium iodide (1) and alcohols or amines 2 is described. Some new amides and esters 3 containing an active iodo functional group have been prepared in 65-91% yields.


Introduction
In the past few decades, much attention has been focused on palladium-catalyzed carbonylation reactions [1,2], which provide a simple method for synthesizing some complicated compounds [3][4][5][6]. These kinds of reactions have been carried out only when the substrates are aryl halides, heteroaryl halides, alkene halides, arylfluoromethylsulfonates and hypervalent iodinium salts, etc. [7], However, the reactions of cross-coupling and carbonyl insertion in one step for iodoheterocyclic compounds has not been reported so far. In the present work, we will describe such a palladium-catalyzed crosscoupling carbonylative insertion reaction between an iodoheterocyclic compound and alcohols or amines.

Results and Discussion
The cross-coupling carbonyl insertion reactions of 3,7-bis(N,N-dimethylamino)-10H-dibenz[b,e] iodinium iodide (1) These carbonylation reactions were carried out smoothly at mild temperature and gave satisfactory yields (65-91%). We examined the influences of catalyst, base and reaction time on this reaction through the cross-coupling of 1 with alcohols. The results obtained under different conditions are summarized in Table 1. Several different Pd-catalysts were used and all of them catalyzed this reaction, but slightly different influences on the yield were observed. Pd(OAc) 2 was the best choice for the reaction. As for the type of base, when the alcohol was 2a, 2b, 2d or 2e, then Bu 3 N, Et 3 N or Na 2 CO 3 could be used. When the alcohol was 2c, only i-PrONa could be used. It was noted that primary alcohols showed much higher reactivity than secondary or tertiary alcohols in this carbonylation. Pd(OAc) 2 Bu 3 N 3.5 3e 65 * Amount of i-PrONa was 0.5 equiv.

Conclusions
An interesting and effective methodology for the synthesis of some new amides and esters, 3, containing an active iodo functional group via the palladium-catalyzed cross-coupling carbonyl insertion reactions between 3,7-bis(N,N-dimethylamino)-10H-dibenz[b,e] iodinium iodide (1) and alcohols or amines 2 is described. This reaction is simple and mild and yields of products 3 are satisfactory.
All reagents were commercially available. The 3, (1) was prepared according to the literature [8]. 1 H-NMR spectra were measured on a FC-80A spectrometer in CDCl 3 with TMS as an internal standard. IR spectra were recorded for KBr pellets on a Nicolet 179SX FT-IR spectrophotometer. Mass spectra were determined on a HP-5988 AG CMS mass spectrometer. Melting points were determined on a Thomas Hoover capillary melting point apparatus and are uncorrected.
General Procedure for the Synthesis of Compounds 3a, 3b, 3d and 3e.
Compound 1 (506mg, 1 mmol), palladium acetate (0.02 mmol) and methanol (20 mL) were mixed under an argon atmosphere at room temperature. After adding Bu 3 N (2 mmol), the inflow of argon was stopped and this gas was replaced with CO (1 atm) and the yellow suspension was stirred for 2h until a clear solution was obtained. The reaction was quenched with aqueous saturated NH 4 Cl solution, then the mixture was extracted three times with Et 2 O and the combined ether layers were dried over anhydrous MgSO 4 . After evaporating the solvent, the crude product was separated by flash chromatography on silica gel using Et 2 O and petroleum ether as eluents to give Similarly the following compounds were prepared:

Synthesis of i-Propyl 2-[4'-(dimethylamino)-2'-iodobenzyl]-4-dimethylaminobenzoate (3c).
Compound 1 (1 mmol), palladium acetate (0.02 mmol) and iso-propanol (20 mL) were mixed under an argon atmosphere at room temperature and then cooled in an ice bath. Sodium iso-propoxide (0.5 mmol) was added and the flask was allowed to warm up to room temperature, then the argon inflow was stopped and this gas was replaced with CO (1 atm.). The yellow suspension was stirred for 1h until a clear solution was formed and then the reaction was worked up as described for 3a to give General Procedure for the Synthesis of Compounds 3h-3n.