Michael cyclization asymmetric

Asymmetric intramolecular Michael cyclization.1 Reaction of the ketone 2 with (R)-( + )-l (1 equiv.) generates an enatnine that adds to the unsaturated ester group to give 3a. The yield and the ee of 3 are markedly improved when 5 A... 

In the same year, Enders and coworkers reported an asymmetric one-pot, two-step synthesis of substituted isoindolines 159 in the presence of chiral A-triflyl phosphoramide (R)-Ae (10 mol%, R = d-NO -C H ) (Scheme 67) [87]. The cascade was triggered by a Brpnsted acid-catalyzed aza-Friedel-Crafts reaction of indoles 29 and A-tosyliminoenoates 160 followed by a DBU-mediated aza-Michael cyclization of intermediates 161 to afford the isoindolines 159 in high yields (71-99%) and short reaction times (10 min to 4 h) along with good enantioselectivities (52-90% ee). Longer reaction times (16 h to 10 days) caused increasing formation of the bisindole byproduct 162 (Scheme 68) along with amplified optical purity of isoindolines 159. 

Yang JW, Hechavarria Fonseca MT, List B (2005) Catalytic asymmetric reductive Michael cyclization. J Am Chem Soc 127 15036-15037 Yoshikawa N, Chiba N, Mikawa T, Ueno S, Harimaya K, Iwata M (1994) Mitsubishi Chemical Industries patent. Jpn Kokai Tokkyo Koho JP 0630600 Zeitler K (2005) Extending mechanistic routes in heterazolium catalysis— promising concepts for versatile synthetic methods. Angew Chem Int Ed Engl 44 7506-7510... 

Scheme 2.10 Oiganocattilytic asymmetric reductive Michael cyclization...

Zhao et al. also presented the asymmetric synthesis of multifunctionalized 47f-pyran derivatives 181 with malononitrile 180 as the nucleophile. The Michael-cyclization reaction of active p,y-unsaturated a-keto esters 179 and malononitrile... 

SCHEME 2.73 Asymmetric Michael-cyclization cascade of a-isothiocyanato imides and methyleneindolinones. 

Scheme 2.7 Asymmetric reductive Michael cyclization and schematic representation of the tandem iminium-enamine catalysis mechanism...

Krische and coworkers [44] developed a Rh-catalyzed asymmetric domino Michael/aldol reaction for the synthesis of substituted cyclopentanols and cyclohex-anols. In this process, three contiguous stereogenic centers, including a quaternary center, are formed with excellent diastereo- and enantioselectivity. Thus, using an enantiopure Rh-BINAP catalyst system and phenyl boronic acid, substrates 2-108 are converted into the correspondding cyclized products 2-109 in 69-88% yield and with 94 and 95% ee, respectively (Scheme 2.24). 

In addition to this, asymmetric 1,3-dipolar cyclization reactions of nitrones with olefins,40 41 catalytic enantioselective cyanation of aldehydes,42 catalytic enantioselective animation,43 and aza-Michael reactions44 have been reported, and high enantioselectivities are observed. 

Comparison with the Hajos-Parrish asymmetric version of the Robinson annulation [81] (Scheme 7.25(a)) shows the following distinct differences between the two methods. Firstly, the cycloalkenone in the Cu(OTf)2/ligand 18-catalyzed procedure is the Michael acceptor, whereas the cycloalkanone is the Michael donor in the proline-mediated annulation. Secondly, the asymmetric induction occurs in the 1,4-addition step in the new method, in contrast to the asymmetric aldol-cyclization in the Hajos-Parrish procedure. 

Scheme 6.141 Mechanistic proposal for the 121-catalyzed asymmetric intramolecular Michael addition exemplified for the model substrates ( )-4-hydroxy-l-phenyl-2-buten-l-one (n = 0) and ( )-5-hydroxy-l-phenyl-2-buten-l-one (n = 1) 121 functions as push/pull-type bifunctional catalyst inducing the cyclization of boronic acid hemiester (1) to form intermediate (2) release ofdiol product (3) by oxidation.

An efficient asymmetric synthesis of the 3-substituted /3-sultams 163 has been reported. The key step of the synthesis is the Lewis acid-catalyzed aza-Michael addition of the enantiopure hydrazines (A)-l-amino-2-methoxy-methylpyrrolidine (SAMP) or CR,l ,l )-2-amino-3-methoxymethyl-2-azabicyclo[3.3.0]octane (RAMBO) to the alke-nylsulfonyl sulfonates 176. /3-Hydrazino sulfonates were obtained in good yield and excellent enantioselectivity. Cleavage of the sulfonates followed by chlorination resulted in the corresponding sulfonyl chlorides 177. The (A)-3-substituted /3-sultams 163 have been obtained in moderate to good yields and high enantioselectivity over two steps, an acidic N-deprotection followed by in situ cyclization promoted by triethylamine (Scheme 55) <2002TL5109, 2003S1856>. 

Tanaka, T. Kumanoto, T. Ishikawa, T. Solvent effects on stereoselectivity in 2,3-dimethyM- chromanone cyclization by quinine-catalyzed asymmetric intromolecular oxo-Michael addition. Tetrahedron-Asymmetry, 2000, 11 4633 637. 

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