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Stereoselectivity of TiCl4-mediated aldol reactions from (S)-2-benzyloxy-3-pentanone is dramatically improved when the reaction is carried out in the presence of 1.1 equiv of tetrahydrofuran (THF) or 1,2-dimethoxyethane (DME). The resultant 2,4-syn-4,5-syn adducts are then obtained in diastereomeric ratios up to 97:3, which proves that the appropriate choice of the Lewis acid (TiCl4-THF or DME vs Ti(i-PrO)Cl3) engaged in the process permits access to both syn-aldol adducts.

Tin(II) complexes prepared by treatment of SnCl2or Sn(SR)2 with appropriate amounts of RSH and Et3N appear to be the best reducing agents for azides (to amines) reported so far. These tin(II) complexes also reduce primary and secondary aliphatic nitro compounds to oximes, usually within minutes at r.t. or hours in cold, and tertiary aliphatic as well as aromatic nitro compounds to afford the corresponding hydroxylamines. In general, azides react more rapidly than nitro substituents, whereas carbonyl groups, sulphoxides, sulphones, nitriles, and esters are practically unreactive under the same conditions. Some mechanistic details of the reaction of Sn(SPh)3- with azides and nitro compounds have also been elucidated.

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.

[reaction: see text] Highly stereoselective approaches directed toward the synthesis of the C18-C27 fragment of superstolide A are disclosed taking ketone 6 and aldehyde 7 as the only sources of chirality.

Addition of the chiral titanium enolate arising from 1 to dibenzyl acetals gives access to anti-b-benzyloxy-a-methyl carbox- ylic adducts in good yields and with diastereomeric ratios up to 99:1. These adducts can be easily converted into a plethora of enan- tiopure protected derivatives. Aldol reaction nowadays constitutes one of the most pow- erful tools for the carbon-carbon bond formation, 1 giving easy access to a-alkyl-b-hydroxy oxygenated moieties present in the molecular architecture of a vast array of nat- ural products. 2 Taking into account that (i) in spite of re- cent advances, the stereoselective construction of anti aldol units is still one of the remaining challenges, 3 and that (ii) the protection of the hydroxyl group of the result- ing aldol adducts is usually required, any methodology able to provide stereoselectively protected anti aldol ad- ducts in a single step would be highly desirable. In this context, we have recently reported that the Lewis acid me- diated cross-coupling reaction of a wide range of dimethyl acetals with the titanium enolate arising from (S)-4-iso- propyl-N-propanoyl-1,3-thiazolidine-2-thione (1) fur- nishes efficiently enantiopure anti-b-methoxy-a-methyl adducts. 4 On the basis of these results, we envisaged that the use of appropriate acetals might lead to a broader va- riety of b-alkoxy-a-methyl carboxylic derivatives, which, in turn, could be considered as protected aldol synthons. Herein, we wish to report that the reaction of the titanium enolate of 1 and dibenzyl acetals affords stereoselectively anti-b-benzyloxy-a-methyl adducts that can be trans- formed into a large number of enantiopure derivatives. Initially, we examined the reaction of 1 with diallyl and dibenzyl acetals derived from benzaldehyde and isobu- tyraldehyde, 5,6 which could afford aldol adducts with eas

4 pages, 2 figures, 2 tables.-- PMID: 12889880 [PubMed].-- Printed version published Aug 7, 2003.-- Supporting information available at: http://pubs.acs.org/doi/suppl/10.1021/ol0347848, Two intramolecular C−H···X (X = O, S) interactions in (S)-N-acyl-4-isopropyl-1,3-thiazolidine-2-thiones are documented through crystallographic and spectroscopic evidence and high-level theoretical calculations. The key role played by the sulfur atoms has been made clear by comparison with structurally related (S)-N-acyl-4-isopropyl-1,3-oxazolidin-2-ones., Financial support from the Ministerio de Ciencia y Tecnología (Grants BQU2002-00293, BQU2002-0485-C02-01, and BQU2002-01514) and from the Generalitat de Catalunya (Grants 2001SGR00048 and 2001SGR00051).

[reaction: see text] Highly stereoselective titanium-mediated aldol reactions based on lactate-derived ketones are reported. The stereochemical outcome of the process depends on the protecting group (PMB or Bn) and the Lewis acid (i-PrOTiCl(3) or TiCl(4)) used in the enolization step, the corresponding anti-syn or syn-syn aldols being prepared in high yields and with diastereomeric ratios up to 99:1.

Comprehensive analysis of the enolization of α-silyloxyketones by Chx2BCl/R3N has allowed us to design stereoselective Chx2BCl-mediated aldol processes that afford syn or anti aldol products and to disclose a hypothesis that accounts for the subtle effects that determine their enolization.

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.

A novel substrate-controlled aldol reaction of a chiral isopropyl ketone is reported. The outstanding regioselective enolization by TiCl4-i-Pr2NEt provides a chelated enolate that can participate in highly diastereoselective additions to a wide array of aldehydes favouring the corresponding 2,5-syn adducts.

Tin(II) complexes prepared by treatment of SnCl2or Sn(SR)2 with appropriate amounts of RSH and Et3N appear to be the best reducing agents for azides (to amines) reported so far. These tin(II) complexes also reduce primary and secondary aliphatic nitro compounds to oximes, usually within minutes at r.t. or hours in cold, and tertiary aliphatic as well as aromatic nitro compounds to afford the corresponding hydroxylamines. In general, azides react more rapidly than nitro substituents, whereas carbonyl groups, sulphoxides, sulphones, nitriles, and esters are practically unreactive under the same conditions. Some mechanistic details of the reaction of Sn(SPh)3- with azides and nitro compounds have also been elucidated.

La nitrosation de carboxamides et de dipeptides est effectuee dans l'acetonitrile en presence d'une base par NOBF 4 /sulfure de methyle ou NO 2 BF 4

La nitrosation de carboxamides et de dipeptides est effectuee dans l'acetonitrile en presence d'une base par NOBF 4 /sulfure de methyle ou NO 2 BF 4

A novel approach to synthesize enantiomerically pure α-hydroxy carboxylic derivatives is reported. A highly stereoselective oxidation of titanium(IV) enolates from chiral N-acyloxazolidinones is performed with oxygen under simple experimental conditions that do not require any reducing steps. The success of this approach depends on the biradical character of titanium(IV) enolates.

Morpholine-derived amides react with RMgX to give the corresponding ketones in good yield. The mild conditions required and low cost of starting materials make this method very appealing for large scale preparations.

Asymmetric syntheses of the C-1 alkyl side chains of Zaragozic acids A and C from a common chiral precursor 4 are reported. The stereoselective reduction of unsaturated ketones 8 and 10 is the key step of both syntheses.