Table 2.

Synthesis of 6-substituted tetracyclines by Michael—Claisen cyclization using D-ring precursors with anion-stabilizing substituents in the benzylic position and enone 1 as substrates, with deprotonation in situ, followed by deprotection [(i) HF (aq), CH₃CN; (ii) H₂, Pd/C, CH₃OH-dioxane].³⁷

D-ring Precursor	Cyclization Conditions	Cyclization Product	Cyclization Yield	Tetracycline	Deprotection Yield
	1; LDA −78 → −10 °C		58%		58%
	1; LDA −78 → −10 °C		72%		60%
	1; LDA −78 → −10 °C		44%		23%
	1; LDA −78 → −10 °C		83%		98%
	1; LDA, TMEDA −78 → −10 °C		25%		64%
	1; LHMDS −78 → −10 °C		72%		43%
	1; LHMDS −78 → −10 °C		38%		65%