Binaphthyl thiourea derivatives

Figure 6.49 Binaphthyl-derived tertiary amine-functionalized bifunctional thiourea derivatives screened in the MBH reaction between 2-cyclohexen-l-one and 3-phenylpropionaldehyde at rt in dichloromethane.

Kim and coworkers have developed a binaphthyl-modified chiral squaramide (20) bearing both central and axial chiralities [89]. The Michael addition of anthrone to nitroalkenes catalyzed by squaramide 20 afforded the products in high yield and good enantioselectivity (Scheme 10.17). Notably, the reaction at lower temperature (0 °C) resulted in a reduced enantioselectivily. This transformation has also been shown to be catalyzed by cinchona alkaloid and thiourea derivatives [90-92]. 

In Ught of the recent developments in thiourea, diol, and phosphoric-acid-mediated catalysis, far fewer studies have focused on the use of chiral carboxyhc acids as suitable hydrogen bond donors. To this end, Mamoka synthesized binaphthyl-derived dicarboxylic acid 49 which catalyzes the asymmetric Mannich reaction of N-Boc aryl imines and tert-diazoacetate (Scheme 5.65) [120]. The authors postulate that catalytic achvity is enhanced by the presence of an addihonal car-boxyhc acid moiety given that use of 2-napthoic acid as catalyst provided only trace amounts of product... 

In 2005, Wang and coworkers reported a new bifunctional binaphthyl-derived amine thiourea 16 as an efficient organocatalyst for the Morita-Baylis-Hillman reaction of cyclohexenone with aliphatic, aromatic and sterically hindered aldehydes. The design of the catalyst follows Takemoto s design of a bifunctional motif. This catalytic protocol provided access to useful chiral allylic alcohol building blocks in high yields and high enan-tioselectivities (Scheme 19.21). 

Nagasawa and co-workers [108] were the first to introduce chiral thiourea catalyst to the BH reaction. They synthesized a tra 5-(li ,2i )-l,2-diaminocy-clohexane-derived bisthiourea 57 as catalyst to promote the BH reaction of cyclohexanone and aldehydes in the presence of DMAP co-catalyst (Scheme 9.31). The dual activations of both substrates were proposed to account for excellent enantioselectivites (for aliphatic aldehydes) and reactivity enhancement. Later on, chiral bisthiourea 58 was prepared and applied as catalyst under solvent-free conditions [109]. Around at the same time, Raheem and Jacobsen [110] demonstrated that chiral thiourea 59 was an efficient catalyst for the DABCO promoted aza-BH reaction of IV-nosyl imines and methyl acrylate. Chiral Hg-binaphthyl bisthiourea 60 was then prepared by Shi and Liu [111] and used as the co-catalyst of DABCO in the reaction of cyclic enones with aldehydes, providing the products in high enantioselectivities. The application of chiral bisthiourea 61 as catalyst resulted in the formation of S configurational products in good to excellent enantioselectivities (Scheme 9.31) [112]. Moreover, thiourea 62 turned out to be an efficient catalyst in the reaction of cyclohex-2-enone with aldehydes co-catalyzed by triethylamine under solvent-free conditions [113]. 

A new catalyst incorporating chiral thiourea and nucleophilic Lewis base showed efficiency in the asymmetric BH reactions. The use of a binaphthyl-based amino-thiourea catalyst 63 synthesized by Wang et al. [ 114] resulted in good yields and enantioselectivities in the reaction of cyclohexenone and aldehydes. Another amino-thiourea 12 was demonstrated as an efficient bifunctional catalyst for the enantio-selective aza-BH reaction of (3-methyl-nitrostyrene and iV-tosyl-aldimines, affording P-nitro-y-enamines in modest to excellent enantioselectivities and diastereoselec-tivities (Scheme 9.32). It was found that no reaction occurred in the absence of the methyl group of nitroalkene [115]. A similar phophine-thiourea catalyst 64 was reported in 2008 by Wu and co-workers [116] and turned out to be efficient in the asymmetric BH reaction of MVK and aldehydes, providing fast reaction rate, good yields, and excellent enantioselectivities (87-94% ee). More recently, aL-threonine-derived phosphine-thiourea catalyst 65 was readily synthesized by Lu and coworkers [117] and applied in the enantioselective BH reaction of aryl aldehyde with methyl acrylate. 

Connon introduced binaphthyl-derived bis-thiourea 31 and demonstrated that it could catalyze the addihon of N-methyhndole to various nitroalkenes, including those incorporating P-aliphahc substituents, although the enantioselectivity was generally moderate (Scheme 7.56) [84]. The utility of 31 was also proven by Wulff through use with a sub-catalytic amount of triethylamine for stereoselectively facilitating the aza-Henry reaction of nitroalkanes with N-Boc imines [85]. 

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