Efficient and Practical Method for Synthesizing Optically Active Indan-2-ols by the Ti(O-i-Pr)₄/2 i-PrMgCl-Mediated Metalative Reppe Reaction

Abstract

An efficient and practical synthesis of optically active indan-2-ols 1 has been developed starting from readily accessible optically active 4-siloxy-1,6-alkadiynes 2 and ethynyl p-tolyl sulfone, where the metalative Reppe reaction mediated by an economical divalent titanium reagent, Ti(O-i-Pr)(4)/2 i-PrMgCl, is a key step.

Zampanolide and dactylolide: cytotoxic tubulin-assembly agents and promising anticancer leads

“…62 The requisite allylsilane 119 for an intramolecular Sakurai cyclisation (IMSC) 60 reaction was obtained from Cu( i )-mediated addition of vinyl Grignard reagent 118 (ref. 63) to chiral epoxide 117 (ref. 64) (Scheme 24).…”

Synthesis of homochiral tris-indanyl molecular rods

“…As a solution we applied a slightly modified protocol developed by Sato and coworkers providing access to the optically active indan-2-ol motif. 24 The epoxide 4 serves as a convenient precursor for the preparation of the optically active indan-2-ol motif and was prepared from commercially available (S)-epichlorohydrin. 24 The first step shown in Scheme 2 is a ring opening of 4 with lithium TBS-propargylide followed by TBS protection providing the 1,6-dialkyne 5 in 73% yield.…”

“…24 The epoxide 4 serves as a convenient precursor for the preparation of the optically active indan-2-ol motif and was prepared from commercially available (S)-epichlorohydrin. 24 The first step shown in Scheme 2 is a ring opening of 4 with lithium TBS-propargylide followed by TBS protection providing the 1,6-dialkyne 5 in 73% yield. Treatment of 5 with an in situ generated divalent titanium species and subsequent addition of Ts-acetylene results in the formation of three new carboncarbon bonds and afforded 6 in 44% yield over two steps.…”

Studies toward the Synthesis of (−)‐Zampanolide: Preparation of the Macrocyclic Core

“…Compound 20 was prepared by addition of trimethylsilyl acetylene anion to ( S )-epichlorohydrin followed by epoxide formation from the subsequent chlorohydrin. 34 Subsequent desilylation and alkyne reduction to the terminal olefin with Cp 2 Zr(H)Cl (Schwartz’s reagent 35 ) afforded hydroxyallylsilane 10 in good overall yield.…”