Domino reactions desymmetrizing

Lautens reported a new enantioselective Rh-catalyzed domino reaction that gives access to fused heterocycles 122 by desymmetrization of alkyne-tethered cyclohexa-dienones 120 [40]. The syn addition of the Rh-aryl species 124 onto the alkyne led to two new C-C bonds and two stereocenters with good enantioselectivity (Scheme 11.25). 

Scheldt s group [50a] described a NHC-catalyzed homonenolate protona-tion/intramolecular aldol/acylation sequence. This domino reaction allowed the desymmetrization of 1,3-diketones by formation of a chiral enol during the process and has recently been used as an efficient strategy for the synthesis of the hydrindane... 

The desymmetrization of dicarbonate 206 was initiated by the addition of one equivalent of N-(3-butenyl) nosylamide 207 under palladium catalysis in the presence of Trost s chiral diphosphine ligand 205. When the first allylic substitution was completed, the reaction was warmed and the resulting intermediate 208 was treated in situ with one equivalent of a second nosylamide 209. Product 210 resulting from this double substitution reaction was submitted to a tandem intramolecular ROM/RCM to furnish key precursor 211, which was engaged in the final cyc-lization step by the reduction of the double bonds, followed by the HCl-promoted domino deprotection of the acetal and aminal formation. 

Chen et al. have further applied the TFA salt of 9-amino-9-deoxyepiquinine lo as chiral organocatalyst to the desymmetrization of prochiral a,a-dicyanoalkenes from 4-substituted cyclohexanones via domino Michael-Michael addition reactions with a, 3-unsaturated ketones. These reactions exhibited high synthetic efficacy and bicyclic products 16 with two new C—C bonds, and four stereogenic centers... 

Cyclopropanes and cyclobutanes were only accessible via xo-type cyclizations, the former only within domino/cascade reactions (see Chapter 8) and the latter being realized by Erase [5a] in desymmetrizing Mizoroki-Heck cyclizations (see Chapter 13) and by Mulzer et al. [5b] five-membered and larger rings are formed in both modes. 

The chapter closes with the application of several of these asymmetric carbon-main-group element bond formations to domino as well as desymmetrization reactions [10, 11],... 

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