Br0nsted acid catalysts cyclizations

Mechanistic details have been disclosed which imply that the cyclization follows a pathway by rapid protonation of one of the carbonyl groups followed by attack of the forming enol at the other carbonyl group <1995JOC301>. The reaction can be carried out under milder conditions and with improved yields using catalysts other than Br0nsted acids and the reaction has been greatly extended in substrate scope. 

In 2009, Klausen and Jacobsen disclosed another activation pathway, in which the thiourea catalyst enhances the acidity of a relatively weak Brpnsted acid catalyst, and applied this to an enantioselective version of the Pictet-Spengler cyclization [149]. This increase on the acidity of the Br0nsted acid allows the protonation of the imine substrate and to the formation of an iminium ion with a chiral counterion, which is stereoselectively attacked by a nucleophile (Scheme 2.28). 

A successful asymmetric organocatalytic based C=0 reduction with the Hantzsch ester was not reported until very recently. Terada and Toda developed a relay catalysis that combined Rh(ll) and a chiral phosphoric acid catalyst in a one-pot reaction (Scheme 32.15). In this reaction sequence, a rhodium carbene (I) forms in the first step and is followed with an intramolecular cyclization to afford carbonyl ylide intermediate II or oxidopyrylium III. These intermediates are protonated by 7 to yield the chiral ion pair between isobenzopyrylium and the conjugate base of 7 (IV). Intermediate IV is further reduced in situ by Hantzsch ester Id to produce the isochroman-4-one derivative 67, which is finally trapped with benzoyl chloride to afford the chiral product 68. Surprisingly, the reaction sequence proceeds well to give racemic product even without the addition of chiral 7, while giving rise to the desired product with high enantioselectivity in the presence of chiral Br0nsted acid 7 [38]. 

The cyclization reaction can be effected thermally or through use of acidic (both Lewis and Br0nsted) catalysts, such as alumina, silica, and boric acid [212-222]. The product mixture contains 70% (—)-isopulegol (172), 23% (+)-neoisopulegol (178), 8% (+)-isoi-sopulegol (179), and 2% (+)-neoisoisopulegol (180). Hydrogenation of this mixture produces a mixture of (—)-menthol (42) from (172) (-l-)-neomenthol (163) from (178) (+)-isomenthol (165) from (179) and (+)-neoisomenthol (167) from (180), as shown in... 

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