Bifunctional tertiary amine

Table 5.7 Bifunctional tertiary amine/thiourea catalyst in MBH reaction of cyclohexenone and selected aldehydes.

In the domino Michael/alkylation reaction applied to the synthesis of 3-(2H)-furanones, the ethyl 4-bromoacetoacetate 203 and nitrostyrene 204 were first trialed with a range of catalysts. In this instance, the so-called modified Feist Binary reaction was completed with an I-threonine bifunctional tertiary amine/thiourea catalyst 205 to produce the furanone 206 in excellent yield and high enantioselec-tivity (Scheme 7.42) [107]. In another report, the furan ring as part of other bicyclic or tricyclic systems was also prepared through an enantioselective Michael addi-tion/nucleophilic substitution reaction (Scheme 7.43) [108]. When diketones and ( )-P,P-bromonitrostyrenes 207 were stirred, again with a bifunctional thiourea... 

More recently, Pihko introduced bifunctional tertiary amine-thioureas 26 and 27 for the Mannich reaction of Boc-imines with malonates. ° Dimethylamino-tertiary amine thiourea 26 proved ideal for aliphatic imines, while the Cinchona derivative 27 provided the best results for aromatic substrates. Catalyst loadings as low as 1 mol% could be employed providing the products in high yields and excellent enantioselec-tivities (Scheme 19.34). Notably, both catalysts presented cooperative assistance via intermolecular hydrogen bonding, as first shown by Smith in 2009. ... 

In 2012, Cobb and co-workers [41] developed a cyclopentanation reaction between nitrostyrenes and E-nitro-a, 3-unsaturated esters (62). The reaction is catalyzed by bifunctional tertiary amine-thiourea catalysts, affording the highly substituted cyclohexanes 63 in good yields and enantioselectivities (Scheme 10.19). 

In addition, an asymmetric Petasis-type transformation of quinolines with vinylboronic acid was developed by Miyabe and Takemoto by using a chiral bifunctional tertiary amine-thiourea, providing the corresponding 1,2-adducts in the presence of phenyl chloroformate as an activator. As shown in Scheme 2.60, the products were obtained in good yields and excellent... 

Barbas and coworkers reported a formal [3-1-2] cyclization between 17a and isothiocyanato imides 53 [24]. The reaction was catalyzed by bifunctional tertiary amine-thiourea catalyst XII and afforded the spiro products 54 in excellent yields and stereoselectivities. The only limitation of the reaction was the use of alkylideneindolones bearing an electron-withdrawing group (Scheme 10.17). 

Wang and coworkers made a similar approach using isocyanoesters [25]. The reaction was catalyzed by bifunctional tertiary amine-thiourea catalysts and afforded the pyrrolidinyl spirooxindoles in good yields and excellent enantioselectivities but low diastereoselectivities. Later, Yan and coworkers developed a similar reaction involving the three-component cascade reaction of isatin, isocyanoesters, and malononitrile [26]. First, the Knoevenagel reaction between isatin and malononitrile afforded the... 

Two complementary thia-Michael/aldol [28] and Michael/aldol [29] strategies from alkylideneindolones involving either a bifunctional tertiary amine-thiourea or the J0rgensen-Hayashi catalyst I have also been proposed contemporaneously. 

Based on the enantioselective Michael addition/ISOC (intramolecular silyl nitronate olefin cycloaddition)/lragmentation sequence previously developed by the group of Rodriguez [33a], Shao and coworkers proposed an extrapolation for the construction of spirooxindoles catalyzed by a bifunctional tertiary amine-thiourea catalyst XV between 4-allyl-substituted oxindoles 63 and nitrostyrenes 64 (Scheme 10.21) [33b]. After the addition of TMSCl and EtgN at -30 C, the Michael adduct underwent an ISCX3 to afford the spiro oxime derivatives 65 in very good yields (85-85%), and excellent diastereo (up to >30 1) and enantioselectivities (94-99% ee) after the treatment with TBAF. 

Alternatively, Wang and coworkers reported a highly enantioselective domino thia-Michael/aldol sequence using bifunctional thiourea-tertiary amine catalysts to afford spirocyclic compound 76 [43]. ( )-Benzylidene chromanone derivatives 74 reacted with 2-mercaptobenzaldehydes 75 in the presence of a bifunctional tertiary amine-thiourea catalyst XVIII. The thia-Michael addition to the benzylidene was followed by an intramolecular aldol reaction between the resulting enolate and the aldehyde moiety. As shown in Scheme 10.26, the reaction afforded the highly functionalized spirocycles in excellent yields and stereoselectivities. 

The same research group developed a new strategy for the synthesis of spirocycles by the addition of a-isothiocyanato imides and esters to unsaturated pyrazolones [52], The reaction was catalyzed by bifunctional tertiary amine-thiourea catalysts to afford the corresponding products in good to excellent yields (72-99%) as well as diastereo (up to >20 1 dr) and enantioselectivities (72-99% ee). 

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