Lithiation ? to heteroatoms: eliminative ring fission of heterocycles

C–H/C–C Functionalization Approach to N-Fused Heterocycles from Saturated Azacycles

“…Notably, as we sought to expand the scope of the annulation reaction to include other α-acylated saturated heterocycles, we found that their reported preparations involved multiple steps as outlined in Scheme that would not be compatible with their generation from a saturated azacycle precursor, especially at a late stage. For example, as shown in Scheme a, the use of a strong base for the α-lithiation in the Beak preparation of α-acylated azacycles severely limits its generality due to the functional group intolerance of these conditions . This limitation also holds for other elegant emerging methods for α-functionalization of saturated azacycles that also rely on the use of strong bases .…”

Intramolecular vinylation of carbanions using N-acyl benzomorpholines as masked vinylureas and vinylcarbamates

“…Florio and co-workers reported that treatment of benzomorpholine 9 or morpholine 11 with LDA at −78 °C leads to enamides 10 and 12 respectively by base-promoted reverse 6endo-trig elimination of the phenoxide anion from a presumed intermediate amide-stabilised organolithium (Scheme 1b). [33] We reasoned that benzylic ureas or carbamates 14 (X = NR or O) containing a benzomorpholine ring might likewise fragment upon treatment with LDA to generate an N-alkenyl urea [28] or carbamate, which could then undergo vinyl migration, ideally in a one-pot procedure (Scheme 1c). In this paper we report our success in developing this strategy for the C-vinylation of some carbanion nucleophiles.…”

“…Purification of this residue by flash column chromatography eluting with (7% to 60% Et2O/Petrol on a SNAP Ultra 10 g column over 13 column volumes) gave the title compound 19; 0.19 g, 64% yield, light yellow solid; Rf 0.20 (30% Et2O/n-pentane); mp 94-96 °C (CH2Cl2/n-pentane); νmax (film)/cm −1 3392, 3059, 1631, 1586, 1538, 1448, 1359, 1242 (33); Carbamate 30 (0.11 g, 0.40 mmol, 1.0 eq.) was added to a dried Schlenk flask under a N2 atmosphere and dissolved in THF (2 mL, 0.2 M).…”

Acyl derivatives of cyclic secondary amines. Part 1. Dipole stabilization of anions: the cumulative effect of two stabilizing groups

“…(lo).-Propane-1,3diamine (3.7 g, 0.05 mol), formalin (37%; 25 ml), and water (150 ml) were stirred at 100 OC for 2 h. Sodium hydroxide (2.5~; 70 ml) was added at -40 "C, and then pivaloyl chloride (12.1 g, 0.10 mol) dropwise. After stirring the mixture at 0 "C for 1 h, column chromatography (alumina and ether) gave hexahydro-1,3-dipivaloylpyrimidine ( 2-Deuterio-1,3-dibenzoylhexahydropyrimidine (8).-1,3-Dibenzoylhexahydropyrimidine (7) by procedure B with D 2 0 as the electrophile gave 2-deuterio- (12).-1,3-Dipivaloylhexahydropyrimidine (10) by procedure A with methyl iodide as the electrophile gave 1,3-dipivaloyl-2-methylhexahydropyrimidine (12) (80% based on recovery of starting material) as needles (from CHCl,), m.p. 125 "C (Found: C, 67.5; H, 10.6; N, 10.3.…”