Morita–Baylis–Hillman Cyclizations of Arene–Ruthenium-Functionalized Acrylamides

Link: http://www3.interscience.wiley.com/cgi-bin/abstract/114182375/ABSTRACT?CRETRY=1&SRETRY=0

From Prof. F. Christopher Pigge's group at University of Iowa

I have read it, although not that thoroughly. From what I saw, this was a strange chemistry, but neat, nonetheless. The paper recently appeared in ACIEE EarlyView. The chemistry involved the Morita-Baylis-Hillman (MBH) reaction performed intramolecularly on acrylamides which are normally difficult substrates to participate in MBH. The enolate intermediate then cyclized to the activated aryl ring by CpRu complex to form a spiroamide-Ru intermediate. Following base-promoted elimination of the alpha-proton and extrusion of the nucleophile promoter, a spiroamide-RuCp complex was obtained. The CpRu could be demetalated to give the highly-functionalized spirolactams. These transformations represent the first examples of direct metal–arene participation in MBH-type reactions.

The first successful reaction conditions is shown in the formation of spiroamide-Ru complex 4.

The choice of solvent was critical and dimethoxyehtane (DME) was found to do the best job. Acetonitrile (MeCN) will also promote the reaction although it gave a lower yield. The nucleophile promoters that worked well were found to be Bu3P and DMAP.

A variety of substrates worked well, even in the aryls containing ortho-substituent. Both electron-rich and -deficient aryl rings also worked well in the reaction. In addition, acrylamides containing beta-substituent, which are normally difficult to react in MBH reaction, reacted smoothly to give the desired products in moderate yields. Substrate containing benzyl substituent was also tolerated.

Next, the substrates containing beta,beta-disubstituted acrylamide were explored as shown in Scheme 3. Dimethyl acrylamide (19a-c) and cyclopentylidene acrylamide (22) readily reacted under the standard MBH conditions to provide the desired products in good yields. In cases of 19a and 19b, the products were obtained as inseparable mixture of alkene isomers. And in case of 22, the elimination in intermediate 24 occurred at H-gamma.

In addition to the 5-membered spirolactam ring, the 6-membered was briefly investigated and two examples were shown to proceed in good to excellent yields (Scheme 4).

The metal complex product could be easily oxidized to yield metal-free organic materials. In the case where an OMe group is present in the para-position, the complex could be demetalated to provide an quinone-like compound.

However, when the OMe group is not present in the periphery, such as compound (S)-16, an oxidation with CuBr2 in water/THF could proceed to afford compound (-)-29 in good yield, with recovery of CpRu fragment.