Development of Cyclic Hydrazine and Hydrazide Type Organocatalyst ⎯ Mechanistic Aspects of Cyclic Hydrazine/Hydrazide-Catalyzed Diels-Αlder Reactions

Abstract

Some hydrazines and hydrazides were prepared and screened for their catalytic efficiencies in Diels-Alder reactions. 1 H-NMR studies and ab initio calculations revealed that catalytic efficiencies of these catalysts are greatly dependent on the release of the catalysts from the Diels-Alder adducts. INTRODUCTION In the early 1970s, two industrial research groups reported the first examples of (S)-proline-catalyzed enantioselective intramolecular aldol reactions. These reactions, so-called Hajos-Parrish-Eder-Sauer-Wiechert reactions, attracted little attention for about 30 years despite their potential values. 1 In the early 2000s, List and coworkers reported (S)-proline-catalyzed intermolecular asymmetric aldol reactions. 2 Thereafter, as well as proline, related five-membered cyclic secondary amine derivatives have also been applied to many reactions that proceed through enamine or iminium ion intermediates. 3 It is well established that a nitrogen atom that is directly bonded to an atom with one or more lone pairs, such as H 2 N-NH 2 and H 2 N-OH, tends to be a stronger nucleophile than would otherwise be expected. The nucleophic enhancement is called "α-heteroatom effect", 4 and such α-nucleophiles seem to be more advantageous as nitrogen-based heterocyclic organocatalysts than simple secondary amine catalysts, but there are not many reported examples. This type of organocatalyst was first reported to promote Diels-Alder reactions efficiently via iminium ions in 2003, 5 and camphor-based chiral hydrazide catalysts were also reported. 6 Recently, we have investigated Biginelli reaction catalyzed by cyclic hydrazine-type organocatalysts as shown in Figure 1, and we have reported that pyrazolidine dihydrochloride 1a could catalyze Biginelli reactions very efficiently under mild conditions. 7 These results promoted us to screen several cyclic hydrazines and hydrazides for their catalytic activities