I. Photochemistry of 2-pyridone and (-)-Crinipellin A synthesis studies. II. Beta-keto amide and enantioselective allylsilane syntheses

Simple 2-pyridone and cyclic dienes can lead to complex cyclooctanes by photochemical [4+4] cycloaddition reaction. The photochemistry of 4-methoxy-2-pyridone and 2-methoxy-naphthalene has been studied. They undergo a [4+4] photocycloaddition largely in a cis fashion to form complex cyclooctane product 69, which is not stable and a Cope rearrangement to give cyclobutane product 70.*; The second part of work involves the synthesis of a chiral pyridone tethered to a furan, which is an important intermediate for the synthesis of (−)-Crinipellin A. During this research: (1) A tethered achiral pyridone and furan 140 has been synthesized and tested for intramolecular [4+4] photocycloaddition. The rapid intramolecular [4+4] cycloaddition of 140 gives cycloaddition products in 81% overall yield. (2) A new two-step method for the synthesis of 2-pyridone has been invented. The condensation of Weinreb amides with dienolates affords γ-acylation product, which is heated in ethanolic ammonia to form 2-pyridones in high yield. (3) A new method for the synthesis of β-keto amides has also been devised. In a modification of the Wirenga-Skulnick β-ketoester synthesis, the dianion of malonic acid mono-amides is condensed with acid chlorides. Acidic workup leads to decarboxylation and isolation of the corresponding β-keto amides in good to excellent yields. A similar procedure with cyanoacetic acid gives β-keto nitriles. (4) A very convergent synthesis of tethered chiral pyridone and furan 250 has been achieved by annulation of an acid dianion and a nitrile alkoxide. Based on Brun's pyridone synthesis and our β-keto nitrile synthesis, the annulation of acid dianion and a nitrile alkoxide proceeds well to give tethered chiral pyridone and furan.*; The third part of work includes the enantioselective synthesis of an allylsilane and determination of its absolute configuration by X-ray. A [3+2] cycloaddition of enantiopure allylsilane and nitrile oxide provides a crystalline product 363, the determination of structure of 363 solves the absolute configuration of the allylsilane. It helps us understand the enantioselective allysilane synthesis process, a reverse-aza-Brook rearrangement developed in Sieburth's Laboratory.*; *Please refer to dissertation for diagrams.