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Opposite Stereochemical Effects Exerted by CeCl 3 and TiCl 4 on the Lewis Acid Mediated Reduction of α‐Alkyl‐β‐ketophosphine Oxides with Metallic Hydrides: A Highly Stereoselective Protocol for the Synthesis of syn and anti α‐alkyl‐β‐Hydroxyphosphine Oxides
Author(s) -
Bartoli Giuseppe,
Bosco Marcella,
Sambri Letizia,
Dalpozzo Renato,
Marcantoni Enrico
Publication year - 1997
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.19970031209
Subject(s) - stereoselectivity , chemistry , lewis acids and bases , alkyl , metal , catalysis , chelation , reducing agent , medicinal chemistry , organic chemistry , stereochemistry
A general, highly efficient methodology for obtaining both syn and anti β‐hydroxyphosphine oxides by reduction of the corresponding β‐ketophosphine oxides is described. The nature of the Lewis acid was found to be pivotal in determining the outcome of these reactions. Strongly chelating TiCl 4 led to the anti isomer in high diastereoisomeric excess in noncoordinating solvents (CH 2 Cl 2 ) at ‐78°C with BH 3 /py as reducing agent, while nonchelating CeCl 3 gave a high excess of the syn isomer in coordinating solvents (THF) at the same temperature with LiBH 4 as reducing agent. In the latter case, CeCl 3 is essential in achieving high yields and stereoselectivity, since it allows the reaction to be performed at low temperatures. Otherwise, higher temperatures (0°C) are required, which lower both yields and selectivities. Moreover, each step of the protocol for the synthesis of stereodefined disubstituted olefins from alkylphosphine oxides (Warren's modification of the Horner procedure) has been optimized, and the optimized procedure has been applied to the synthesis of muscalure, the pheromone of the domestic fly.