Practical enantiospecific synthesis of RPR 111905: A novel non-peptide substance P antagonist

An Easy, Stereoselective Synthesis of Hexahydroisoindol‐4‐ones under Phosphine Catalysis

“…Intermediate A1 should undergo then an intramolecular Michael-type addition leading to A2. A formal [1,4]-proton shift will then convert A2 into A3 and create a negative charge b to the phosphorus centre. The phosphine elimination step achieves the cyclization process.…”

“…[2] Common synthetic strategies (Scheme 1) toward saturated fused bicyclic amines of this class mainly involve the 1,3-dipolar cycloaddition of azomethine ylides on suitable cyclic olefins [3] or DielsAlder type reactions on maleimide. [4,5] A new, alternative and practical synthesis of hexahydro-4H-isoindol-4-one derivatives is reported hereafter, based on phosphine catalyzed [3 + 2] cyclizations [6] which involve imines and dienes as the twoatom and three-atom components, respectively. The method has been unexpectedly brought to light while expanding the scope of the recently disclosed reaction between electron-poor conjugated dienes and imines, under phosphine catalysis, shown in Scheme 2.…”

Synthesis of Enantiomerically Pure Cyclohex‐2‐en‐1‐ols: Development of Novel Multicomponent Reactions

“…Selected examples of the obtained 1-amido-cyclohex-2-ene derivatives have been successfully applied in the synthesis of anilines, [4] phthalic acid esters, [5] and cyclohexenylamines. [6] Moreover, this type of MCR product is of interest for the synthesis of pharmaceutically attractive molecules like dendrobine, [7] pumiliotoxin C, [8] phenanthridones, [9] and nonpeptide NK1 P-antagonists, for example, RPR 111905 [10] (Scheme 1). So far, the scope of the AAD reaction has been limited to the use of 1-(N-acylamino)-1,3-butadienes as key intermediKeywords: cyclohexenes · enzymes · kinetic resolution · multicomponent reactions Abstract: Multicomponent reactions of aldehydes, dienophiles, and alcohols or carboxylic acid anhydrides have been developed for the first time.…”

Efficient One-Pot Synthesis of Substituted 1-Acylaminocyclohex-2-enes

“…The obtained products are of interest as precursors and analogues of biologically active natural products such as RPR 111905. 12 The reactivity of ketones in AAD-type reactions has not been explored in detail so far. Nevertheless, the example given in the bottom line of Scheme 6 illustrates an extension of the general procedure to a,b-unsaturated ketones, though at elevated temperatures (160°C).…”