Structurally Divergent Lithium Catalyzed Friedel–Crafts Reactions on Oxetan‐3‐ols: Synthesis of 3, 3‐Diaryloxetanes and 2, 3‐Dihydrobenzofurans. Issue 45 (10th October 2016)

• Record Type: Journal Article
• Authors: Croft, Rosemary A.; Mousseau, James J.; Choi, Chulho; Bull, James A.
• Is Part Of: Chemistry. Volume 22:Issue 45(2016)
• Page Start: 16271
• Page End: 16276
• Publication Date: 2016-10-10
• Subjects: carbocations -- homogeneous catalysis -- lithium -- oxetanes -- oxygen heterocycles; Chemistry -- Periodicals; 540
• DOI: 10.1002/chem.201604031
• Languages: English
• ISSNs: 0947-6539

Abstract

Abstract: The first examples of 3, 3‐diaryloxetanes are prepared in a lithium‐catalyzed and substrate dependent divergent Friedel–Crafts reaction. para ‐Selective Friedel–Crafts reactions of phenols using oxetan‐3‐ols afford 3, 3‐diaryloxetanes by displacement of the hydroxy group. These constitute new isosteres for benzophenones and diarylmethanes. Conversely, ortho ‐selective Friedel–Crafts reactions of phenols afford 3‐aryl‐3‐hydroxymethyl‐dihydrobenzofurans by tandem alkylation–ring‐opening reactions; the outcome of the reaction diverging to structurally distinct products dependent on the substrate regioselectivity. Further reactivity of the oxetane products is demonstrated, suitable for incorporation into drug discovery efforts. Abstract : Double the benefit : 3, 3‐Diaryloxetanes are prepared as isosteres of benzophenones and diarylmethanes, through inexpensive lithium catalyzed Friedel–Crafts reaction (see figure). Complementary dihydrobenzofurans are also prepared, highly selectively, with the product dependent on the substrate regioselectivity. The oxetane products are stable to further derivatization reactions, suitable for incorporation into drug discovery efforts.