Organocatalysts urea-derived

Scheme 6.29 Range of products for the DABCO-promoted MBH reaction utilizing urea derivative 16 as hydrogenbonding organocatalyst. The results of the uncatalyzed reference reactions are given in parentheses.

This survey illustrates all (thio)urea derivatives discussed in the chapter (Thio) urea Organocatalysts. ... 

Several organocatalysts have been recycled efficiently (selected examples are shown in Scheme 14.2). For example, the Jacobsen group has reported results from an impressive study of the recycling of the immobilized urea derivative 6, a highly efficient organocatalyst for asymmetric hydrocyanation of imines (Scheme 14.2) [11]. It was discovered that the catalyst can be recycled and re-used very efficiently - over ten reaction cycles the product was obtained with similar yield and enantioselectivity (96-98% yield, 92-93% ee). 

In 2005, the groups of Connon [38] and Dixon [39] independently reported that epi-cinchona-based (thio)urea derivatives can serve as excellent bifunctional organocatalysts... 

Moreover, the same authors employed a closely related organocatalyst and the corresponding urea derivative to promote the enantioselective dynamic kinetic resolution of azalactones with allylic alcohol. In this case of substrates, the urea derivatives proved to be superior to their thiourea analogues and, most usefully, these catalysts were insensitive to the steric bulk of the amino acid residue, allowing alanine-, methionine- and phenylalanine-derived azalactones to undergo dynamic kinetic resolution with unprecedented levels of enantioselectivity, as shown in Scheme 9.4. Furthermore, the compatibility of these catalysts with thiol nucleophiles was exploited in the first enantioselective catalytic dynamic kinetic resolution of azalactones by thiolysis to furnish enantioenriched amino acid thioesters of potential use with moderate enantioselectivities (<64% ee). 

Mine [7] and Kelly [8] were the first to prepare synthetic equivalents of this bidentate motif, using biphenylene diols as catalysts. Shortly after Etter had studied the hydrogen bonding patterns in supramolecular assemblies of various carbonyl compounds [9, 10], Curran introduced diarylurea derivatives as further bidentate organocatalysts [11, 12]. This interplay between supramolecular chemistry and non-covalent catalysis has turned out to be very fruitful ever since [13-15]. Schreiner subsequently showed that thioureas are also potent organocatalysts, which offer several advantages compared to urea derivatives, e.g., better solubility [13, 16]. In a proof-of-principle study, thiourea derivative 1 (Fig. 1, right) was used to catalyze the Diels-Alder reaction shown in Scheme 1 [16]. 

Figure 6.3 Stereoselective, chiral thiourea derivatives of achiral benchmark thiourea organocatalyst N,N -bis [3,5-(trifluoromethyl)phenyl]thiourea 9 stereoselective hydrogen-bonding thiourea organocatalysts incorporating the privileged 3,5-bis(trifluoromethylphenyl)thiourea moiety. The (thio)urea catalyst structure is the leitmotif for the chapter organization.

Urea 32, the bis-(mono-trifluoromethyl)phenyl derivative of urea catalyst 16 [178], was reported to operate as double hydrogen-bonding organocatalyst in the diastereoselective synthesis of y-butenolide products substituted at the y-position... 

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). 

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