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DOI: 10.1055/s-0030-1260385
Crotylation and Homopropargylation by Flow Technology
Rezensent(en):Yasuhiro Uozumi, Yoichi M. A. YamadaUniversity 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
Publikationsverlauf
Publikationsdatum:
19. Mai 2011 (online)
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).