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Chiral α-silyloxy ketones participate in highly stereoselective TiCl4-mediated aldol reactions that afford diastereomerically pure syn–syn adducts in high yield irrespective of the R1 and R2 substituents flanking the carbonyl or the silicon protecting group. Further manipulation of the resulting aldol adducts provide in a straightforward manner highly functionalized fragments that facilitate the synthesis of natural products.

Titanium-mediated aldol reactions based on (S)-2-tert-butyldimethylsilyloxy-3-pentanone, a lactate-derived chiral ketone, provide the corresponding 2,4-syn-4,5-syn adducts in high yields and diastereomeric ratios with a wide array of achiral and chiral aldehydes. Furthermore, spectroscopic studies of intermediates involved in the process have permitted to propose a mechanism that accounts for the experimental results.

Highly stereoselective titanium-mediated aldol additions of ethyl ketones derived from lactic acid to α-methyl-β-OTBDPS chiral aldehydes are documented. One of these double stereodifferentiating processes represents the key step of a straightforward and efficient synthetic approach to the C1-C6 fragment of erythronolides.

New syntheses of densely functionalized protected derivatives of 3-amino-3,6-dideoxyaminosugars have been accomplished in an efficient and straightforward manner. The key step of such approaches involves a highly stereoselective titanium-mediated aldol addition of a chiral α-bromo ketone, easily available from lactate esters, to crotonaldehyde. Further functional group transformations, including a new regioselective Staudinger–aza-Wittig reaction of an azidodiacetate, afford in a few steps and high yield the desired carbohydrates as advanced intermediates capable of participating in subsequent glycosylation reactions.

The influence of substitution pattern of α-siloxy ketones on the reactivity in Ti-mediated aldol reactions is studied.

Highly diastereoselective (i-PrO)2TiCl2-mediated aldol reactions from lactate-derived α′-halo α-silyloxy ketones and subsequent treatment of the resultant aldols with a wide range of nucleophiles f...

Highly diastereoselective (i-PrO)(2)TiCl(2)-mediated aldol reactions from lactate-derived alpha'-halo alpha-silyloxy ketones and subsequent treatment of the resultant aldols with a wide range of nucleophiles furnishes highly functionalized arrangements useful in natural product syntheses.

Alternative titanium-mediated aldol procedures based on several protected beta-hydroxy ethyl ketones have been surveyed. Eventually, enolization of (S)-1-benzyloxy-2-methyl-3-pentanone (1) with (i-PrO)TiCl3/i-Pr2NEt provided a very reactive enolate that afforded the corresponding 2,4-syn-4,5-syn aldol adducts in high yields and diastereomeric ratios with a broad range of aldehydes.

Experimental and theoretical studies evidence an unconventional biradical character for the titanium enolates derived from α-alkoxy ketones and TiCl4. EPR experiments and ab initio calculations suggest that these titanium enolates have an open shell electronic ground state.