Terminal Heck Vinylations of Chelating Vinyl Ethers

Abstract

Terminal chelation-controlled Heck vinylations of electron-rich amino-functionalized vinyl ethers were performed with high regioselectivity furnishing moderate to good isolated yields of the corresponding 1-alkoxy-1,3-butadienes. DFT calculations support an amine-palladium(II) coordination strength reactivity/selectivity rationale, where the dimethylamino group was the preferred metal presenting functionality. Controlled microwave heating effectively accelerated these palladium-catalyzed reactions and full conversion could be achieved within 30 minutes.Subsequent Diels-Alder reactions with dimethyl acetylenedicarboxylate under microwave irradiation resulted exclusively in partly aromatized bi-and tricyclic compounds by elimination of the aminoalkoxy group. Thus, the selected dimethylamino auxiliary both controlled the regiochemistry in the palladiumcatalyzed vinylation and was easily displaced in the aromatization process.

Directed Mizoroki–Heck Reactions

“…The C -C double bond of 15b is coordinated by the cationic palladium reagent (20 → 22, Scheme 4); alternative precoordination of the tertiary amine by 20 is omitted for the sake of clarity. Without the amine donor coordinated to the palladium catalyst, the regioselectivity of alkene insertion is controlled by electronic (and steric) factors as in a usual intermolecular Mizoroki-Heck reaction favoring regioisomer α-16b [23][24][25][26]. The palladium complex 22 is in equilibrium with another tetracoordinate complex 23, in which one of the phosphanyl groups of the bidentate diphos-phane is substituted by the intramolecularly available amino group.…”

“…A series of vinyl ethers 15 and 17 was arylated under so-called Jeffery conditions [34] (15 → 16 and 17 → 18, Scheme 2). Substrates 15a (n = 1) and 17a (n = 1) devoid of a coordinating group (Do = CH) were chosen as reference systems since their electronically controlled [35] aryla-Scheme 2 Amino-and pyridyl-directed, regioselective Mizoroki-Heck reactions by Hallberg [23][24][25][26] tion provides a mixture of regioisomers. This poor regioselectivity improved dramatically with the installation of an sp 3 - [36] or sp 2 -hybridized [37] nitrogen as in 15b (Do = N, n = 1) or as part of a pyridyl moiety in 17b (Do = N, n = 1).…”

“…1), which is capable of coordinating the palladium catalyst. This then allows for intramolecular delivery of the aryl/vinyl fragment 1 thereby mimicking an intramolecular Mizoroki-Heck reaction, a scenario that has been coined by Hallberg as a chelation-controlled Mizoroki-Heck reaction [23][24][25][26]. This review will summarize the evolution of this concept from achieving the initial objective of controlling regioselectivity to recent diastereoselective and even enantioselective directed Mizoroki-Heck reactions.…”

“…With regard to synthetic usefulness, the intramolecular Mizoroki-Heck reaction has undoubtedly outshone many other efforts in the wide-ranging area of MizorokiHeck chemistry. One of these underappreciated areas, which has recently been going through a second childhood, was systematically introduced by Hallberg several years ago [23][24][25][26]. In order to control the regioselectivity of an intermolecular Mizoroki-Heck reaction, Hallberg designed an alternative to intramolecular Mizoroki-Heck processes by installation of a suitable donor Do in the alkene fragment 2 (2 ⇒ 4, Fig.…”

Recent Developments in Microwave‐Assisted, Transition‐Metal‐Catalysed C–C and C–N Bond‐Forming Reactions

“…The same principle of chelation control was applied by Larhed and co-workers to the synthesis of a set of 1-alkoxy-1,3-butadienes by microwave-assisted Heck vinylation of electron-rich amino-functionalized vinyl ethers (Scheme 35). [48] The reactions were performed with high regioselectivity. The resulting dimethylaminoethoxy-1,3-butaScheme 35.…”