Use of Nobin and Related Species as Asymmetric Phase-Transfer Catalysts

Use of Nobin and Related Species as Asymmetric Phase-Transfer Catalysts 

Under solid-liquid phase-transfer conditions, amino adds 17 and 25a,b were obtained from reactions using benzyl bromide, allyl bromide and 1-chloromethylnaphthalene, respectively, as the alkylating agents in the presence of 10 mol% of (S)-Nobin. Products 17 and 25a were obtained with 90% yield and 67-68% ee, whilst product 25b was obtained in only 60% yield and with only 18% ee, presumably due to the lower reactivity of the benzylic chloride-based alkylating agent. 

A mechanistic investigation of the Nobin-catalyzed alkylation of substrate 11a revealed that the reaction displays an extremely large positive non-linear effect [25], 

This is caused by the two enantiomers of Nobin forming a very stable - but catalytically inactive - heterochiral dimer, thus removing the minor enantiomer of Nobin from the catalytic cycle and leaving the major enantiomer of Nobin to form a complex with the sodium ion and the enolate of substrate 11a. From a practical perspective, the non-linear effect means that amino adds with essentially identical enantiomeric excesses are obtained whether the Nobin catalyst is enantiomerically pure or has an enantiomeric excess of just 30%. Since Nobin is prepared as a racemate [26,27] and must be resolved [27,28] prior to use, this is a major synthetic 

The use of Nobin as a catalyst for the Michael addition of the enolate of substrate 11a to methyl acrylate was also investigated, but only relatively low levels of asymmetric indudion (up to 45%) were observed [30], In contrast, iso-Nobin derivatives 27a-d were found to give much better results in this reaction [30,31], For the Michael addition of methyl acrylate to substrate 11a, the N-acylated iso-Nobin derivatives 27b-d were found to be more enantioselective than the use of iso-Nobin 27a. Under 

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