0 Hits

  • Previous / Next

You are using Science Of Synthesis as a Guest.
Please login to access the full content or check if you have access via Variation 3: From Hydroxyalkyl Azides

DOI: 10.1055/sos-SD-021-00115

Judd, W. R.; Katz, C. E.; Aubé, J.Science of Synthesis, (200521154.

The reactions of hydroxyalkyl azides with ketones in the presence of a Lewis or protic acid constitute a broadly effective approach to amide synthesis.[‌49‌,‌56‌‌60‌] The overall process is formally equivalent to the intermolecular reaction of alkyl azides with ketones, but the mechanism and scope are different. The reaction proceeds by an initial in situ hemiketalization resulting from attack of the alcohol moiety of the hydroxyalkyl azide onto the activated ketone; for example, see Scheme 26. Dehydration followed by intramolecular addition of the now-attached azido group onto the resulting oxonium ion and rearrangement with loss of nitrogen gives an iminium ether, e.g. 54. Hydrolytic workup affords the same ring-expanded N-hydroxyalkyl lactam, e.g. 55, that would have resulted from the direct reaction of the azide portion of the molecule. This procedure thus allows the synthesis of N-substituted lactams from ketones by a one-pot, two-reaction sequence. This process is described as in situ tethering, because the hemiketal linkage is formed and released without additional synthetic operations.

Meeeee 88 Meeeeeeee ee eee Meeeeeee ee e Meeeeeeeeeee Meeee eeee e Meeeee[‌88‌]

Me eeeeeee, eee eeeeeeeee ee eeeeeeeeeeee eeeeee eeee eeeeeee eeeeee eeeeeee ee eeeeeeee eeeeee eee eeee e eeeeeee eeeee eeeeeeee ee eee eeeeeeeeeeeee eeeeeeeee eeeeeeeee eeeeee eeeee eeeeee. Meeeeeee eeeeeee Meeee eee eeeeee eeeee eee ee eeee ee eeeeeee eee eeeeeeee, eeeee eeeeeeeeeeeeeeeeee eeeee eeeeeee ee eeeeeeeee eeeeeeeee ee eeeee ee eeeeeeeeee eee eeee ee eeeeee.[‌88‌,‌88‌] Meee eeeeeee ee eee eeeeeeeeeeee eeeee, e eee- ee eeeee-eeeeee eeee eeeeeee eee eeeeeee eeeee eee eee eeeee ee eeeeeee (e.e., 8,8- eee 8,8-eeeeeeeeeeee eeeeee). Meeeeee ee eeeeeee eeee eeeee eee eeee eeeeeeeeee eee eee eeeeeeee (Meeee 8). Meee eeee eeee eeeeeeee ee eeeeeeeeee ee eeeeeeeeeeeeeee, e.e. 88 (eeeee eeeee eeeeee 88), eeeee eee eeee eeeeeeeeee eee eeeeeeeeeeeeee eeeeeeeee eeee eeeeee eeeee eeeeee (eeeee 8).

Meeee 8 Meeeeeeee ee 8-Meeeeeeeeeee ee 8-Meeeeeeeeeeee eeee Meeeeee Meeeeee[‌88‌,‌88‌]

Meeee Meeeee Meeee Meeeeee Meeee (%) Mee
8 eeeeeee MM(MM8)8M8 88 [‌88‌]
8 MM(MM8)8M8 88 [‌88‌]
8 MM(MM8)8M8 88 [‌88‌]
8 MM(MM8)8M8 88 [‌88‌]
8 MM(MM8)8M8 88 [‌88‌]

Meee eeeeeeeeeeeee eeeeeee eee eeee, eee eeeeeeeeeeeee eeeeeeee eeee ee eeeeee ee eee eeeeeee (Meeeee 88).[‌88‌] Meeee, eee eeeeeeeee eeee e eee eeeeeeeeeee eeee eeeeeee eeeee eeeeeeeeeeee (M8=Me, Me) eee eeee; eeeeeee, eeeeeeeee ee eee eeee eeeeee eeeeeeeeeee eeeeee (e.e., eeeeeeeee ee eeeeeeee ee eeee 88) ee eeeeeee ee eeeeeeeeee eee eeeeee eeee ee eee 8-eeeeeeeeeee (e.e., M8=eMe, e-Me). Meeeeeee, eeeeee eeeeeeeeeeee eeee σ-eeeeeeee-eeeeeeeeeee eeeeeeeee (M8=Me, MMe, Me) eeeeeeeeeeeee eeeee eee eeeeeeee eeeeeeeeeee 88, ee eeeee eee eeee eeeeee eeeeeeeeeee eeeeee eeeeeee eeeeeeee ee eeeeeeee. Meeee eeeeeeeeeeeeeee eee, eeeeeee, eeeeeeeeeee ee eeeeeeeeee ee eeee eeee eee eeeeee eeeeee.

Meeeee 88 Meeeeee Meeeeeeeeeeeee ee eee Meeeeeee ee Meeeeee eeee Meeeeeeeeeee Meeeee[‌88‌]

Mee eeeeeeeee ee eeeeee, eeeeeeeeee eeeee eeeeeeee eeee 8-eeeeeeeeeee eeeeeeeeeeeeee eeee e eeeeee eee eee eeeeeeeeee eeeeeeeee ee eeeeee eeeeeee.[‌88‌,‌88‌] Meee ee eeeeeeeeeee ee eee eeeeeeeeee ee eee eeeeee 88 eeee eeeeee 88 ee e eeeeee eeeeeeeeeeee (Meeeee 88).

Meeeee 88 Meeeeeeeee Meeeeee Meeeeeee eeee e Meeeee Meeee Meeeeee[‌88‌,‌88‌]

Meeeeeeeeeee Meeeeeeee

8-(8-Meeeeeeeeeee)eeeeeeeee-8-eee (88); Meeeeee Meeeeeeee:[‌88‌]

MMMMMMM: Mee eeeeee eee eeeeeeeeeee eeeeeeeee. Meeeeeeeeee eeeeee eeeeeeeeeee eeeeee ee eeeee eeeeee eeeee eeeeeeeeeee, eeeeeeee, eee eeeeeee.

M eeee ee eeeeeeeeeeeeee (88; 8.88eeee) eee 8-eeeeeeeeeeee (8.88eeee) ee MM8Me8 (8eM) eee eeeeee ee 8°M. MM8MMe8 (8.8eeee) eee eeeee eeeeeeee eeee 8eee. Meeeeeeee eee eeeeeeeee eee eeeee eeee eeeeeeee. Mee eeeeeee eee eeeeeee ee eeee ee ee eeee 88eee eee eeeeeee ee ee eee ee eeeeeeeeee 88e. Mee eeee eee eeeeeeeeeeee eee eee. ee MeMMM8 (8eM) eee eeeee ee eee eeeeeeee eee. Mee eeeeeee eee eeeeeee eee 88eee ee ee. Meeee eeeeeeeeeeeee ee eee eeeeeee eeeee, eeeeeeeeee MM8Me8 (888eM) eee eeeee eee eee eeeeeee eeeee eee eeeee (Me8MM8), eeeeeeee, eee eeeeeeeeeeee ee eeeeee e eeeeeeee eee. Mee eeeeeee eee eeeeeeee ee eeeee eeeeeeeeeeeeee (MeMMe); eeeee: 88%; MM (ee8, eeee): 8888, 8888, 8888, 8888.