Novel Domino Elimination-Rearrangement-Addition Reaction of N-Alkoxy(arylmethyl)amines to N-Alkyl Arylamines

Abstract

A new domino reaction of N-alkoxy(arylmethyl)amines to N-alkyl arylamines, consisting of three types of reactions: elimination of alcohol, rearrangement of the aryl group, and addition of an organolithium or a magnesium reagent, has been developed for the first time.

Key words

domino reaction - N-alkoxyamine - Grignard reagent - organolithium reagent - rearrangement

References and Notes

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10

N-Butyl-1-phenylethylamine was also obtained in 11% yield as a minor product. This product would be formed by substitution of the methoxy group with an n-butyl group. P. Beak [11] and co-workers reported nucleophilic displacement of alkoxide by the alkyl group at the nitrogen atom in the alkoxyamines.

12

Typical Procedure for Domino Elimination-Rearrangement-Addition Reaction of 4, N -Dimethoxy-α-methyl Benzenemethanamine(3b) with n -BuLi (entry 4 in Table 1).
To a stirred solution of 3b (45 mg, 0.25 mmol) in Et₂O (1.7 mL) was added n-BuLi (1.6 mol/L in n-hexane; 0.47 mL, 0.75 mmol) under a nitrogen atmosphere at r.t. After being stirred at the same temperature for 15 min, the reaction mixture was diluted with H₂O at 0 °C and extracted with CHCl₃. The organic phase was dried over MgSO₄ and concentrated under reduced pressure. Purification of the residue by PTLC (n-hexane-EtOAc, 6: 1) afforded 4c (44 mg, 85%) as a pale yellow oil. IR: ν_max = 3393 cm^-1. ¹H NMR (200 MHz): δ = 6.77 (2 H, br d, J = 9.0 Hz), 6.55 (2 H, br d, J = 9.0 Hz), 3.74 (3 H, s), 3.36 (1 H, sext, J = 6.0 Hz), 1.60-1.27 (6 H, m), 1.14 (3 H, d, J = 6.0 Hz), 0.90 (3 H, t, J = 6.0 Hz). ¹³C NMR (50 MHz): δ = 152.2, 144.0, 115.3, 114.9, 55.7, 50.0, 36.6, 28.3, 22.7, 20.5, 14.0. HRMS: m/z calcd for C₁₃H₂₁NO [M⁺]: 207.1624; found: 207.1626.

15

Yamamoto [8] group has employed O-ethoxycarbonyl-N-benzyl-N-cycloalkylhydroxylamines as substrates, which have no hydrogen atom on a nitrogen atom. Substrates of our newly found reaction need the secondary amino moiety. Thus reaction pathway of our domino reaction using organolithium and organomagnesium reagents would be completely different from Yamamoto’s reaction. [8]