A New and Highly Effective Aldol Synthesis

Abstract

A new approach has been demonstrated for the regiospecific aldol synthesis by the simultaneous addition of α-halo carbonyl derivatives and aldehydes or ketones to a suspension of diethylaluminum chloride and zinc in tetrahydrofuran at low temperature. This technique is also employable under mild conditions for the Reformatsky reaction to give β-hiydroxy esters in excellent yield. One of the unique synthetic applications of this process is illustrated by the intramolecular cyclization of α-bromo esters of ω-hydroxy aldehyde, which produces macrolides, an important class of compounds in the antibiotic field.

The Chemistry of α-Haloketones and Their Utility in Heterocyclic Synthesis

“…Regiospecific cross aldol-type condensation have been demon-strated by the simultaneous addition of α-haloketones and aldehydes or ketones to a mixture of diethylaluminum chloride and zinc [ 556 , 557 , 558 ], or by means of Bu 3 SnAlEt 2 complex [ 559 , 560 , 561 ], titanium(II) chloride [ 562 ], Co(0) [ 563 ], Sm(II) [ 564 ], In(0) [ 565 ], CrCl 2 [ 566 ] or cobalt(0) trimethylphosphine complex [ 567 , 568 ] to give similar results of the kinetic crossed aldol products 305 ( Scheme 89 ).…”

Exclusive α-Coupling in the Aldol Reaction of Unsaturated Trimethylsilyl Esters: An Efficient and Practical Direct Synthesis of Unsaturated β-Hydroxy Acids

“…In all cases, hydroxy acids 1 were obtained as a mixture of two diastereomers (syn and anti). Since suitable crystals were not obtained for rigorous assignment by X-ray spectroscopy, the crude hydroxy acids were converted into their corresponding methyl esters, whose configurations had previously resolved. ,, The ratio of syn/anti was determined by 1 H NMR: the chemical shifts of the vinylic hydrogen (CH−) are larger for the syn unsaturated acids than for the anti isomers. As shown in Table , modest selectivity in favor of the syn isomer was observed with most of the aldehydes used.…”

The Chemistry of α‐Haloketones and Their Utility in Heterocyclic Synthesis

“…The reaction proceeds via the cross aldol condensation mechanism (Scheme 88) [549][550][551][552][553][554][555]. Regiospecific cross aldol-type condensation have been demonstrated by the simultaneous addition of α-haloketones and aldehydes or ketones to a mixture of diethylaluminum chloride and zinc [556][557][558], or by means of Bu 3 SnAlEt 2 complex [559][560][561], titanium(II) chloride [562], Co(0) [563], Sm(II) [564], In(0) [565], CrCl 2 [566] or cobalt(0) trimethylphosphine complex [567,568] to give similar results of the kinetic crossed aldol products 305 (Scheme 89). Sodium hydrotelluride [574], tin dichloride/sodium sulfite (SnCl 2 /Na 2 SO 3 ) [575] or cerium trichloride [576] furnished similar results.…”