Ring Enlargement of Enantiopure 1,2-Oxazines to 1,2-Oxazepine Derivatives and Their Palladium-Catalyzed Couplings

Abstract

Phase-transfer-catalyzed cyclopropanation of enantio­pure 1,2-oxazine derivatives anti-1a,b or syn-1 followed by solvo­lysis of the resulting geminal dibromocyclopropane intermediates afforded the expected ring-expanded products, namely 1,2-oxazepines anti-3a,b or syn-3. These heterocycles could be further substituted by use of their bromoalkenyl group employing ­palladium-catalyzed coupling reactions, which smoothly led to new enantiopure 1,2-oxazepine derivatives anti-4-anti-8.

dibromocyclopropanes - ring enlargement - 1,2-oxazines - 1,2-oxazepines - palladium catalysis

References

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Typical Procedure, conversion of anti -1a into anti -3a.
A solution of NaOH (0.60 g) and KF (4.10 g) in H₂O (4.10 mL) was added to a vigorously stirred solution of anti-1a (0.50 g, 1.64 mmol) in CHBr₃ (2.70 mL) containing benzyltriethylammonium chloride (5.5 mg). The biphasic mixture was stirred for 2 d at r.t. and then diluted with H₂O (8 mL) and extracted with Et₂O. The combined ethereal extracts were washed with brine, dried (Na₂SO₄) and concentrated. The excess CHBr₃ was removed in vacuum. The residue was purified by column chromatography (silica gel, hexane-EtOAc, 4:1) to give 2a as colorless liquid (511 mg, 65%, dr 68:32).
Dibromocyclopropane derivative 2a was refluxed for 20 h in a solution of anhyd K₂CO₃ (0.87 g, 6.27 mmol) in MeOH (7 mL) under Ar atmosphere. The mixture was cooled to r.t., diluted with H₂O and extracted with CH₂Cl₂. The combined organic extracts were dried (Na₂SO₄) and concentrated. The product was purified by column chromatography (silica gel, hexane-EtOAc, 9:1) to yield 241 mg (53%) of anti-3a as colorless oil.
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