Aza Morita Baylis Hillman

Other successful H-bond catalysis apphcations have been introduced by Schaus and Sasai involving asymmetric Morita-Bayhs-Hilhnan (Scheme 11.13c) and aza-Morita-Baylis-Hillman reactions (Scheme 11.13d), respectively. Intriguingly, derivatized BINOL systems 33 and 34 provided optimal selectivities. 

NHC catalyzed reactions have been expanded to include reactions such as aza-Morita-Baylis-Hillman and Mnkaiyama aldol reactions. Ye and co-workers illustrate the utility of NHCs in a reaction that is traditionally catalyzed by amines and phosphines (Scheme 52) [169],... 

In related work, Sasai developed several bifunctional BINOL-derived catalysts for the aza-Morita-Baylis-Hillman (aza-MBH) reaction [111]. In early studies, careful optimization of the catalyst structure regarding the location of the Lewis base unit revealed 41 as an optimal catalyst for the aza-MBH reaction between acyclic a,P-unsaturated ketones and N-tosyl imines. Systematic protection or modification of each basic and acidic moiety of 41 revealed that all four heterofunctionalities were necessary to maintain both chemical and optical yields. As seen in Scheme 5.58, MO calculations suggest that one hydroxyl groups forms a... 

P-Amino carbonyl compounds containing an a-atkyUdene group are densely functionalized materials, which are widely applied in the synthesis of medicinal reagents and natural products [265]. These products are usually prepared through the classic aza-Morita-Baylis-Hillman reaction [176, 177] of activated imines and electron-deficient alkenes catalyzed by tertiary amines or phosphines. Chen and co-workers, in 2008, identified bis-thiourea 106 as a suitable catalyst for the... 

M. Shi and Y.-L. Shi reported the synthesis and application of new bifunctional axially chiral (thio) urea-phosphine organocatalysts in the asymmetric aza-Morita-Baylis-Hillman (MBH) reaction [176, 177] of N-sulfonated imines with methyl vinyl ketone (MVK), phenyl vinyl ketone (PVK), ethyl vinyl ketone (EVK) or acrolein [316]. The design of the catalyst structure is based on axially chiral BINOL-derived phosphines [317, 318] that have already been successfully utilized as bifunctional catalysts in asymmetric aza-MBH reactions. The formal replacement of the hydrogen-bonding phenol group with a (thio)urea functionality led to catalysts 166-168 (Figure 6.51). 

Chiral BINOL (60) is a bifunctional organocatalyst in addition to the phenolic Brpnsted acid groups, it has a Lewis base unit attached via a spacer moiety.167 This particular combination holds the groups in a conformational lock, where they can doubly activate a substrate while giving a high level of stereocontrol. For this example of an aza-Morita-Baylis-Hillman reaction of an enone and an imine, yields up to 100% and ees up to 96% have been achieved. 

A series of A - / - n i trobe nzenesul fony 1 imincs have been reported to undergo asymmetric aza-Morita-Baylis-Hillman reactions with methyl acrylate mediated by DABCO in the presence of chiral thiourea organocatalysts with unprecedented levels of enantioselectivity (87-99% ee), albeit only in modest yields (25 19%). Isolation of a DABCO-acrylate-imine adduct as a key intermediate, kinetic investigation, and isotopic labelling, have been employed to determine the mechanism.177... 

Asymmetric aza Morita-Baylis-Hillman reactions of N-sulfonylimines or N-sulfinimines with Michael accepters in the presence a Lewis base catalyst to give the corresponding chiral a-methylene-/ -amino compounds have been described [27]. 

Another class of bifunctional organocatalysts for the enantioselective aza-Morita-Baylis-Hillman reaction of imines (112) with enones (113) (Scheme 6) is based on BINOL (115). The efficiency of the catalysts proved to be mainly influenced by the position of the Lewis basic moiety attached to the BINOL scaffold. The activation of the substrate by acid-base functionalities and the fixing of conformation of the catalyst (115) are apparently harmonized to maximize the enantiocontrol (<95% ee) 52... 

According to another NMR study, the mechanism of bifunctional activation in the asymmetric aza-Morita-Baylis-Hillman reaction (Scheme 7) involves rate-limiting proton transfer (116) in the absence of added protic species155 (in consonance with the report summarized in Scheme 5144), but exhibits no autocatalysis. Addition of Brpnsted acids led to substantial rate enhancements through acceleration of the elimination step. Furthermore, it was found that phosphine catalysts, either alone or in combination with protic additives, can cause racemization of the reaction product by proton exchange at the stereogenic centre. This behaviour indicates that the spatial arrangement of a bifunctional chiral catalyst for the asymmetric aza-Morita-Baylis-Hillman reaction is crucial not only for the stereodifferentiation within the catalytic cycle but also for the prevention of subsequent racemization.155... 

A NHC-catalyzed aza-Morita-Baylis-Hillman reaction (aza-MBH) following a standard nucleophile-mediated MBH mechanism has been disclosed very recently (He et al. 2007). Although combined with a preceding equilibrium for the reversible formation of imine-carbene adducts this reaction has similarities with phosphines and their organo-catalytic reactivity (Methot and Roush 2004). 

He L, Jian TY, Ye S (2007) A-Heterocyclic carbene catalyzed Aza-Morita-Baylis-Hillman reaction of cyclic enones with A-tosylarylimines. J Org Chem 72 7466-7468... 

Morita-Baylis-Hillman Reactions and Aza-Morita-Baylis-Hillman Reactions... 

Propose a mechanism for the following formation of the aza Morita Baylis Hillman reaction product that is obtained from an a hydroxypropargylsilanc (1) and the N tert butanesulfinyl imine. Provide the structure of intermediate A obtained upon slow addition of n BuLi to ( ) 1. 

Chiral Amines Derived from Asymmetric Aza Morita Baylis Hillman Reaction... 

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