BINOL Morita-Baylis-Hillman-reaction

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. 

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. 

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... 

Table 6.32 BINOL-catalyzed Morita-Baylis-Hillman reactions of cyclic enones.

Sasai developed an enantioselective Morita-Baylis-Hillman reaction of a,p-unsaturated ketones by using chiral heterobimetallic boron(m) lithium(i) binaphtholate 21, which was prepared from LiB(s-Bu)3H and (I )-BINOL (Scheme 2.16). The a-methylene-p-hydroxy ketones were obtained with up to 99% ee. 

Among all catalysts containing phenol groups, the best results in terms of yields and asymmetric inductions were obtained with molecules containing a binaphthol scaffold. Inspired by the seminal work of Yamada et on the Morita-Baylis-Hillman reaction between cyclic enones and aldehydes promoted by a cooperative catalytic system of tributylphosphine and phenols (including rac-BINOL), McDougal and Schaus reported the first example of an asymmetric Morita-Baylis-Hillman reaction using chiral BINOL and binaphthol derivatives 38 as catalysts, in the presence of triethylphosphine as nucleophilic promoter (Scheme 24.15). 

Scheme 24.15 Catalytic asymmetric Morita-Baylis-Hillman reaction with modified BINOL catalysts.

But, Yukawa et al. used lanthanum isopropoxide/BINOL system, 128, for the catalysis of asymmetric aza-Morita-Baylis-Hillman reaction (reaction 7.28), in which the electron-deficient alkenes, 129, reacted with... 

In the catalytic asymmetric aza-Morita-Baylis-HiUman reaction using unactivated methyl acrylate, the combined use of a La(0- Pr)3/(5, 5 )-TMS-linked-BINOL complex with a catalytic amount of l,4-diazabicyclo[2.2.2]octane (DABCO) promoted the aza-Morita-Baylis-Hillman reaction of a broad range of A-diphenylphosphinoyl imines." ... 

Amino-a-methylene carbonyl compounds have been prepared in up to 92% ee via an aza-Morita-Baylis-Hillman reaction. A-Tosyl imines of, y-unsaturated a-ketoesters have been reacted with acrolein in the presence of two catalysts / -isocupridine (a chiral quinolol containing a DABCO moiety) and a bifunctional BINOL (or a 3 amine-thiourea). NMR and MS evidence supports a self-assembly of the catalysts, giving a multi-functional supramolecular catalyst. 

Schaus et al reported enantioselective Morita-Baylis-Hillman reaction by means of a BINOL derivative (36) in the coexistence of a stoichiometric amount of PEts (Scheme 2.79) [147]. 

Sasai et al developed a bifunctional BINOL-derived organocatalyst (37) and reported an aza Morita-Baylis-Hillman reaction (Scheme 2.80) [148]. While the 3-pyridyl moiety functioned as a Lewis basic site, the diol moiety worked as a Bronsted acidic site. It is noted that introduction of N-isopropyl-N-3-pyridinylaminomethyl moiety at the 3-position is essential for attaining excellent enantioselectivity. They subsequently introduced 2-diphenylphosphinophenyl group onto the third position and successfully utilized it in the aza Morita-Baylis-Hillman reaction [149]. 

In 2003, Schaus and coworkers utilized Binol-derived hydrogen-bond donors 6a and 6b along with triethylphosphine in the enantioselective Morita-Baylis-Hillman reaction of cyclohexenone with various aldehydes (Scheme 10.8) [67]. Control experiments showed that the use of mono-methylated diols resulted in significant decreases in both the yields and enantioselectivities. 

The ability of chiral binaphthoi (BINOL) derivatives as a Br0nsted acid catalyst to facilitate asymmetric transformations was demonstrated by Schaus by the development of the highly enantioselective Morita-Baylis-Hillman reaction of cyclohex-enone with aldehydes effectively catalyzed by (J )-octahydro-l,T-bi-2-naphthol derivatives, bearing either 3,5-bis(trifluoromethyl)phenyl (24a) or 3,5-xylyl (24b) groups at the 3,3 -positions, in combined use with triethylphosphine as a nucleophilic promoter (Scheme 7.43) [68]. 

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... 

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). 

Chen and coworkers published a formal [3 + 3]-type reaction to give highly substituted cyclohexenes 8. This domino process consists of an allylic-allylic alkylation of an a,a-dicyanoalkene derived from 1-indanone and Morita-Baylis-Hillman carbonates, following an intramolecular Michael addition, by employing dual orga-nocatalysis of commercially available modified cinchona alkaloid (DHQD)2AQN If (hydroquinidine (anthraquinone-l,4-diyl) diether) and (S)-BINOL. The cyclic adducts... 

Bifunctional organocatalysts, particularly, (S)-3-(N-isopropyl-N-3-p5nidi-nylaminomethyl) BINOL for enantioselective aza-Morita-Baylis-Hillman (aza-MBH) reactions 07Y1089. 

The aza-Morita-Baylis-HiUman reaction is known to be a useful and atom-economical C-C bond-forming reaction of electron-deficient alkenes with imines usually catalyzed by Lewis bases [202]. It formally involves a sequence of reactions including a Michael addition, a Mannich reaction, a proton transfer, and a retro-Michael reaction ( -elimination). Although there are many reports in the field of the enantioselective aza-Morita-Baylis-Hilhnan reaction, only rare examples of asymmetric domino reactions initiated by this reaction have been reported. In 2010, Sasai et al. [203] developed the first organocatalyzed asymmetric domino aza-Morita-Baylis-Hillman/aza-Michael reaction of a,p-unsaturated carbonyl compounds with N-tosylimines, allowing an easy access to chiral cis-1,3-disubstituted isoindolines as single diastereomers. The process was induced by a Hg-BINOL-derived catalyst and provided these products in high yields and enantioselectivities, as shown in Scheme 10.18. 

Ikegami et al. reported an asymmetric Morita—Baylis—HUlman reaction using a BlNOL-calcium complex as a chiral Lewis acid and tributylphosphine as an achiral Lewis base (Scheme 2) [24]. It was found that an active calcium aryloxide catalyst could be prepared from Ca(0 Pr)2 and (f )-BINOL in THF. The reaction of cyclopentenone with 3-phenylpropionaldehyde was tested in the presence of the calcium complex, and the desired Morita-Bayhs-Hillman adduct was obtained in 62 % yield with 56 % ee. 

Shibasaki et al. also developed chiral barium catalysts prepared from barium alkoxide and optically active BINOL 3 or aryloxide 4 derivatives. These catalysts were applied to asymmetric Mannich reactions of p,y-unsaturated esters (Table 27) [101]. In this reaction, the initially formed Mannich adducts isomerized to afford aza-Morita-Baylis-Hillman-type products in moderate to good yields with good enantioselectivities. For four substrate examples, ayloxide 4 ligand worked well (entries 2—4). 

Schaus and coworkers have developed a general route to the Clerodane diter-pene core by the use of previously developed B rousted acid catalyzed asymmetric Morita-Baylis-Hillman (MBH) reaction/Lewis acid mediated ring-annulation process (Scheme 1.33) [31]. Excellent diastereoselectivity was achieved in the key MBH reaction in the presence of 10mol% of the chiral BINOL derivative (29), affording the key intermediate for the synthesis of Clerodane decalin core. 

---