Bobbitt modification

The Bobbitt modification is the most widely used variation of the Pomeranz-Fritsch reaction. This modification involves cyclisation of benzylaminoacetal 10, usually prepared from the classical Pomeranz-Fritsch imine 9, to yield 4-hydroxy derivatives 11. The success of this method can be attributed to avoiding treatment and thus (partial) destruction of imine 10 under strongly acidic conditions. 

The total synthesis of (+)-4-hydroxycrebanine was accomplished by J.-l. Kunitomo et al., who used the Bobbitt modification of the Pomeranz-Fritsch reaction as the key ring-forming step. The aromatic ketone substrate was first condensed with aminoacetaldehyde diethylacetal to afford a Schiff base that was immediately reduced to the corresponding amino compound in high yield. Exposure of this intermediate to concentrated HCI for several days gave rise to the tetrahydroisoquinoline as a mixture of two diastereomers. 

Jackson modification and Schlittler-Muller modification. The Fischer modification involves the treatment of benzalaminoacetal with fuming sulfuric acid, whereas Bobbitt modification produces tetrahydroisoquinoline derivative through the hydrogenation of an imine intermediate in situ to an aminoacetal, which in turn is converted into product by the acid-promoted cyclization and hydrogenation. This modification for tetrahydroisoquinoline is also known as the Pomeranz-Fritsch-Bobbitt cyclization. The Schlittler-Muller modification involves the preparation of benzalaminoacetal from benzyl amines and gly-oxal semiacetal. In addition, this reaction has been extended to prepare other types of aromatic heterocycles, such as thieno[2,3-c] and thieno[3,2-c]pyridines by intromolecular cyclization to thiophene ring. ... 

This reaction has been modified to different variants, such as the Bobbitt modification, Fischer modification, and the Schlittler-Muller modification. In addition, different acids have been used as the promoters for this reaction. 

Dyke and Tiley have successfully used the Bobbitt modification of the Pomeranz-Fritsch cyclization in a synthesis of berberastine. The deoxybenzoin 21 was condensed with aminoacetaldehyde dimethyl acetal and the resulting Schiff base was reduced with borohydride to give amine 22. The remaining key steps were a Mannich condensation and a Pomeranz-Fritsch acid-catalyzed cyclization ... 

The Jackson modification involves cyclisation of iV-tosylated amine 12 and provides a complementary method to the classical Pomeranz-Fritsch reaction for entry into the fully unsaturated ring system 13. Amine 12 can be prepared from either the Pomeranz-Fritsch-Bobbitt imine 10 or reaction of benzylhalide 14 and the corresponding sodium anion 15. ... 

Gluszynska, A., Rozwadowska, M. D. Enantioselective modification of the Pomeranz-Fritsch-Bobbitt synthesis of tetrahydroisoquinoline alkaloids synthesis of (-)-salsolidine and (-)-carnegine. Tetrahedron Asymmetry 2000,11,2359-2366. 

The synthesis of ( )-hexahydropronuciferine (119) (Scheme 10) has been reported utilizing Bobbitt s modification of the Pomeranz-Fritsch reaction as... 

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