Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• environment for the reaction to occur. The first part of this section will focus on the asymmetric 1,4-addition of carbon nucleophiles and the next two parts will discuss the addition of amines (aza-Michael addition) and phosphorous compounds. 2.4.1 Asymmetric 1,4-addition of carbon nucleophiles: Since its

• -unsaturated amides or other carboxylic acid derivatives. This section will focus on the most significant findings that have been reported on the Lewis acid catalyzed aza-Michael additions of α,β-unsaturated amides and lactams [231][232]. One of the first examples of an aza-Michael addition to α,β-unsaturated

• Jørgensen group reported the first aza-Michael addition of secondary aryl amines [234]. The authors obtained the 1,4-addition products in moderate to high yields and enantioselectivities by using a nickel–DBFOX–Ph [235][236] catalyst (Scheme 30). Other chiral ligands have been used in addition to chiral

Organocatalytic cascade aza-Michael/hemiacetal reaction between disubstituted hydrazines and α,β-unsaturated aldehydes: Highly diastereo- and enantioselective synthesis of pyrazolidine derivatives

• Zhi-Cong Geng,
• Jian Chen,
• Ning Li,
• Xiao-Fei Huang,
• Yong Zhang,
• Ya-Wen Zhang and
• Xing-Wang Wang

Beilstein J. Org. Chem. 2012, 8, 1710–1720, doi:10.3762/bjoc.8.195

• explored by several groups [72][73]. In 2007, Jørgensen et al. reported that the organocatalyzed asymmetric aza-Michael addition of hydrazones to cyclic enones had been achieved in good yield and stereoselectivity [74]. In 2011, the Deng group developed a highly enantioselective organocatalytic synthesis

Coupled chemo(enzymatic) reactions in continuous flow

• Ruslan Yuryev,
• Simon Strompen and
• Andreas Liese

Beilstein J. Org. Chem. 2011, 7, 1449–1467, doi:10.3762/bjoc.7.169

• and solvent-free environment [38]. In the first noncatalyzed thermal aza-Michael addition performed at 80 °C, the racemic ester rac-46 is formed from cheap starting materials benzylamine (44) and trans-ethylcrotonate (45) (Scheme 14). Subsequently, Novozym 435 is applied for the kinetic resolution of

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• used. A proper choice of catalyst and reaction conditions is also needed to improve the efficiency of each reaction (Scheme 18) [18]. Consecutive one-pot transformations initiated by Heck reaction and terminated by intramolecular aza–Michael addition were developed by Hanson and coworkers to access a

• sulfur dioxide. However, this Pd-catalyzed aminosulfonylation process proved inefficient with primary amines (Scheme 20) [20]. Multicomponent synthesis of nitrogen-containing heterocycles may also be initiated by an aza-Michael addition and terminated by a palladium-catalyzed ring-closure process [21

Single enantiomer synthesis of α-(trifluoromethyl)-β-lactam

• Václav Jurčík,
• Alexandra M. Z. Slawin and
• David O'Hagan

Beilstein J. Org. Chem. 2011, 7, 759–766, doi:10.3762/bjoc.7.86

• explored as the enantiomerically pure amine. In the event 4a was generated after aza-Michael addition as a mixture of two stereoisomers, without any obvious diastereoisomeric bias (1:1, 0% de) as judged by both 1H and 19F NMR. β-Lactam ring closure, using thionyl chloride and triethylamine gave the N

• is reported which took advantage of an aza-Michael addition between (S)-α-(p-methoxyphenyl)ethylamine (3b) and α-(trifluoromethyl)acrylic acid (2). Cyclisation and then chromatographic resolution of the β-lactam diastereoisomers 5b, followed by deprotection with ceric ammonium nitrate generated the β