Protic Acid Promoted Cyclizations

B. Lewis or Protic Acid Promoted Cyclizations 1. Synthesis of IndoloquinoUzines... 

Scheme 16 Protic acid-promoted cyclizations of germacranolides...

Thiazoles are deactivated towards electrophilic substitution, and thus direct reaction with hydride re-ductants to give thiazolines should be facilitated. There are indeed some examples of this type of reaction, but it is more common to reduce N-alkylated thiazolium salts (209). These compounds are converted first by reaction with sodium borohydride into 4-thiazolines (210), which in protic solvents become protonated and undergo further reduction to yield thiazolidines (211). Similarly the isoquinoli-nium salt (213), formed by the acid-promoted cyclization of the isoquinoline (212), is converted into the tetrahydroisoquinoline (214) (presumably via an intermediate 1,2-dihydroisoquinoline) by reaction with sodium borohydride. ... 

OZTs from aldoses and ketoses. The second and the oldest-as well as the less studied—method is based on the condensation of O-unprotected sugars with thiocyanic acid, generated in situ from potassium thiocyanate and a protic acid. The reaction involves the free anomeric position and a y- or (5-hydroxyl group able to promote intramolecular cyclization of a transient open-chain isothiocyanate, to form the thermodynamically most stable OZT. The first results obtained by Zemplen in d-gluco and D-Fru series reported the formation of OZTs fused to pyran backbones (Scheme 20).42... 

Alko xy ally 1)stannane aldehydes (57) can cyclize either thermally or with Lewis or protic acid catalysis to give cyclic ethers (58).85 The interrelationship of the reactant and product stereochemistries has been investigated, as have the methods used to promote the reaction. For both thermal and proton-promoted reactions, [(Z)-57 gave (cis-58), and [(E)-57] gave trans-58), whereas trans-58) was the predominant or exclusive product of Lewis acid mediation, regardless of the double bond geometry of... 

Propargylsilanes show predictable behavior as cyclization terminators. Internal additions of propy-nylsilanes to acyclic -acyliminium ions promoted by Lewis acids or protic acids yield a-allenic amides or carbamates (Scheme 54). ... 

Protic acids have also been used to intramolecularly promote the cyclization of a nitrile with an azide. Chlorosulfonic acid was used to promote the intramolecular cyclization of a few substrates into their tetrazoles. Note that the presence of chlorosulfonic acid along with the intramolecular nature... 

However, the ability of gold(III) chloride to provide protic catalysis under exceptionally mild conditions is further demonstated by two recent examples the hydroxyallene 35 bearing a silyl protecting group is efficiently cyclyzed to give the 2,5-dihydrofuran 36 without deprotection [20] other acidic catalysts which in principle sufficiently promote this type of cyclization - such as HC1 gas or Amberlyst 15 resin - are of course much less compatible with acid sensitive functionalities. Also for the formation of macrocycle 39 gold(III) chloride turned out to be the catalyst of choice [21],... 

Kinetic isotope measurements for the cyclocondensation step of the Knorr pyrrole synthesis suggest that two protic solvent molecules participate in a rate-determining ketone protonation before cyclization and dehydration. Chiral SPDqOL-phosphoric acids (39) promote asymmetric Pictet-Spengler reactions (Scheme 27). i... 

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