Crotylation and Homopropargylation by Flow Technology

doi:10.1055/s-0030-1260385

Synfacts 2011(6): 0685-0685
DOI: 10.1055/s-0030-1260385

Polymer-Supported Synthesis

Crotylation and Homopropargylation by Flow Technology

Contributor(s):Yasuhiro Uozumi, Yoichi M. A. Yamada

C. F. Carter, H. Lange, D. Sakai, I. R. Baxendale, S. V. Ley*
University of Cambridge, UK and Mitsubishi Tanabe Pharma Corporation, Yokohama, Japan
Diastereoselective Chain-Elongation Reactions Using Microreactors for Applications in Complex Molecule Assembly
Chem. Eur. J. 2011, 17: 3398-3405

Abstract

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Key words

microreactor - flow chemistry - asymmetric synthesis - chain elongation

Significance

A new flow reaction technology for diastereoselective Roush crotylation and Marshall homopropargylation as well as in-line purification protocols was described. Thus, the flow Roush reaction of aldehydes 1 with boronate 2 gave the corresponding homoallyl alcohols 3 in 70-94% yield with syn selectivity (syn/anti = 3.6-20:1). Similarly, the diastereoselective flow Marshall homopropargylation of allene (P)-4 with aldehyde (S)-5 was carried out with BF₃˙OEt₂ to give homopropargyl alcohol 6 in 75% yield.

Comment

An automated multi-step flow protocol [(1) the reduction of ester (S)-7 with DIBAL; (2) the purification with IRA-743/SiO₂; (3) the treatment with boronate 2a in a microreactor; (4) the purification with IRA-743] afforded 3a in 78% yield. The authors indicated that flushing the pumps, valves, and reaction coils with isopropyl alcohol, followed by acetone and then the dry solvent of choice under an inert atmosphere for at least two hours was needed for a suitable process (to eliminate all traces of water from the reactor).

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