Aldol condensation, directed

Trifluoromethyl alkyl ketones also undergo directed aldol condensations under thermodynamic conditions in the presence of piperidine and acetic acid [2, d] Under these reaction conditions, the product suffers a facile dehydration to form the unsaturated trifluoromethyl ketones (equations 2 and 3)... 

Since the first reported directed aldol condensation using lithiated imines1. few methods concerning the diastereo- and enantioselectivity of their addition to aldehydes and ketones have been published. 

The aldol reaction can be applied to dicarbonyl compounds in which the two groups are favorably disposed for intramolecular reaction. Kinetic studies on cyclization of 5-oxohexanal, 2,5-hexanedione, and 2,6-heptanedione indicate that formation of five-membered rings is thermodynamically somewhat more favorable than formation of six-membered rings, but that the latter is several thousand times faster.170 A catalytic amount of acid or base is frequently satisfactory for formation of five- and six-membered rings, but with more complex structures, the techniques required for directed aldol condensations are used. 

Reaction of aldehydes and 2 equivalents of ketone in the presence of 5 mol% of (R)-BaBM gives good yield of aldol product (77-99%) with moderate enan-tioselectivity (54-70% ee) after a 2-day reaction (Scheme 3-36 and Table 3-9). Although the enantioselectivity is not very high, this is one of the first examples of direct aldol condensation using barium catalyst as the promoter. 

Enolates also serve as suitable reaction partners in a directed aldol condensation (Eq. 52) 88) Dehydration of the aldol 51 to give enone (POCl3, HMPA then C5H5N) followed by reduction [LiAlH(nC4H9) (iC4H9)2] produces a vinylogue of a cyclopropylcarbinol 53. Aqueous fluoroboric acid smoothly rearranges 53 to the... 

Directed Aldol Condensations with Preformed Lithium Enolates in the Presence of Zinc Chloride... 

DIRECTED ALDOL CONDENSATIONS THREO-4HYDROXY-3PHENYL-2-HEPTANONE... 

DIRECTED ALDOL CONDENSATIONS threo-4-HYDROXY-3-PHENYL-2-HEPTANONE, 54, 49 DIRECTED LITHIATION OF AROMATIC COMPOUNDS (2-DIMETHYL-AMINO- 5-METHYLPHENYL) DI-PHENYLCARBINOL, 53, 56 DIRECT IODINATION OF POLYALKYL-BENZENES IODODURENE, 51, 94 Disiamylborane, 53, 79 Disodium hydroxylaminedisulfo-nate, 52, 83... 

Mixed aldol reactions may be broadly classified as the reaction between two different aldehydes or ketones, or the reaction of an aldehyde with a ketone. Apart from the concomitant self-condensation, not less than two possible crossed products can be envisaged. Such reactions are therefore only prepara-tively useful either if appropriate structural conditions are present, or if certain experimental conditions are used to effect a directed aldol condensation. 

A cationic rhodium complex, [(Me5Cp)Rh(j/6-benzene)]2+, catalyses direct aldol condensation of ketones.153... 

Saito, S. Shiozawa, M. Ito, M. Yamamoto, H. Conceptually new directed aldol condensation using aluminum tris(2,6-diphenylphenoxide). J. Am. Chem. Soc. 1998, 120, 813-814. 

SCHEME 119. Chiral enolate directing aldol condensation synthesis of Hapalosin573... 

Another use of imines is in a directed aldol condensation reaction, directing the condensation in a way that the aldehyde, after reacting with the base, will react with the other carbonyl compound, with no self-condensation. Imines, in contrast to their precursors, aldehydes, are too weak electrophiles to undergo self-condensation. However, after lithiation with LDA, the lithium salts 19 are sufficiently good nucleophiles to react... 

---