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Synfacts 2011(6): 0685-0685  
DOI: 10.1055/s-0030-1260385
Polymer-Supported Synthesis
© Georg Thieme Verlag Stuttgart ˙ New York

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  
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Publication History

Publication Date:
19 May 2011 (online)

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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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