Acetate aldol reaction

Pseudoephedrine proprionamide (39) has been employed as a chiral auxiliary in asymmetric acetate aldol reactions.135... 

In addition to being an efficient chiral controller in a number of stereoselective transformations of chiral acrylates, (i.e. the Diels-Alder reaction, the conjugate reduction, the asymmetric dihydroxylation, and the nitrile oxide cycloaddition ) the bomanesultam (11) has been shown to be an exceptionally efficient chiral auxiliary for stereoselective aldol condensations (eqs eq 3 and eq 4). Depending upon the reaction conditions, A -propionylsultam can produce either the syn or anti aldol product with an excellent diastereoselectivity, Furthermore, good diastereoselectiv-ities are also observed for the corresponding acetate aldol reaction (eq 5), ... 

Other approaches to the bryostatins have also used enantio- or diastereoselective aldol reactions. An interesting iterative strategy for the synthesis of the Cj-Cg polyacetate region 134 has been disclosed where each aldol addition proceeds with excellent stereocontrol (99 1) under the catalytic influence of oxazaborolidine 135 (Scheme 9-42) [60J. Finally, a moderately selective, auxiliary controlled, acetate aldol reaction has been used for the introduction of the C3 stereocenter of the bryostatins giving adduct 136 (84% d.s) [61]. 

A highly diastereoselective acetate aldol reaction that uses an L-tert-leucine-derived N-acetyl thiazolidinethione auxiliary 125 and dichlorophenylborane has been reported <04OL23>. Thiazolidinethione reagent 127, pseudoenantiomeric to 125, is also found to be effective in diastereoselective asymmetric aldol reactions, thus obviating the expensive D-tert-leucine <04OL3139>. Asymmetric aldol additions of A-propionyl thiazolidinethione... 

The key asymmetric acetate aldol reaction was carried out using Carreira s conditions (Scheme 12-1) to give 4 in nearly quantitative yields and perfect enantioselectivity, followed by hydrolysis to acid ent-5. This is the enantiomer of the fragment present in the natural products. Because of later difficulties with the macrolactonization, that step was carried out under Mitsunobu conditions with inversion of the alcohol, hence necessitating the opposite stereochemistry in precursor ent-5. 

Scheme 12-3 The Canesan and Doi-Takahashi procedures for enantioselective acetate aldol reactions with aldehyde 3.

Tin(II) Enolates of A Acyloxazolidinethiones. Tin(II) enolates of 7V-oxazolidinethiones show moderate diastereos-electivity for the non-Evans aldol products (eqs 5 and 6), presumably proceeding through a chelated transition state. The A(-acetyl oxazolidinethiones are generally less selective than the corresponding thiazolidinethiones in diastereoselective acetate aldol reactions. 

An interesting feature of the Crimmins thiazoldinethione is that either the Evans syn or non-Evans syn adducts can be prepared through a variation in the amount of (-)-sparteine (or other diamine bases, such as DIEA and TMEDA) utilized. The yields, diastereoselectivities and enantioselectivities of the reaction are generally high and can be used in the acetate aldol reaction. ... 

Stereoselective Acetate Aldol Reactions Using Chiral Auxiliaries... 

The early tvork in the field of titanium enolate acetate aldol reactions tvas conducted by Braun in a general investigation of acetate aldol reactions [12]. The enoiates tvere generated from chiral acetamide 16 by transmetalation of the lithium enolate tvith triisopropoxytitanium chloride or titanium tetrachloride, as sho vn in Table 2.3. They reported moderate selectivity for the reaction vith benzaldehyde. 

Yan and covrorkers developed titanium enolate acetate aldol reactions as an extension of their boron acetate enolate methodology [13, 14]. Good yields and diastereoselectivity vere reported vhen using camphor-derived N-acyloxazolidinethione 19 (Scheme 2.3, Table 2.4, entries 1-7, and Figure 2.1). The high selectivities vere attributed to additional chelation afforded by the thiocarbonyl of the chiral auxiliary in transition state assembly 20, sho vn in Scheme 2.3. The corresponding camphor-derived oxazolidinone acetate imide provided no stereocontrol, supporting the chelation control hypothesis. 

Shortly thereafter, acetate aldol reactions using camphor-derived imidazo-lidinone 27 vere reported by Palomo and co vorkers [15]. They reported moderate yields and enantioselectivity for a variety of unsaturated and aliphatic aldehydes (Table 2.4, entries 8-12). Interestingly, enantioselectivity for unsaturated aldehydes vas opposite that for aliphatic aldehydes. Also, enantioselectivity reported for titanium vas completely opposite that of the corresponding lithium enolate reactions. 

Survey of acetate aldol reactions employing chiral auxiliaries. 

Chiral auxiliaries used in the asymmetric acetate aldol reactions described in Table 2.4. 

Camphor-derived asymmetric acetate aldol reactions. 

Urpi and Vilarassa investigated an asymmetric acetate aldol reaction in conjunction vith the synthesis of Macrolactin A [17]. They reported good yield and excellent stereoselectivity for a handful of unsaturated aldehydes using a valine-derived thiazolidinethione chiral auxiliary. 

Stereoselective Acetate Aldol Reactions Involving Chiral Titanium Ligands... 

Duthaler and co vorkers demonstrated that stereoselectivity in the titanium enolate acetate aldol reaction could also be induced by chiral ligands on titanium [18]. Their cyclopentadienylbis(l,2 5,6-di-0-isopropylidene-a-D-... 

Sterically hindered oxazolidinethione-derived asymmetric acetate aldol reactions. S O... 

Transition-state models of the asymmetric acetate aldol reaction. 

Stereoselective acetate aldol reactions involving chiral titanium Lew/is acids. 

Recently, Ghosh and Kim developed an alternative procedure for acetate aldol reactions utilizing ester-derived titanium enolate aldol reactions [25]. As sho vn in Scheme 2.5, reaction of chloroacetate 55 vith TiCU and diiso-propylethylamine provided the titanium enolate, vhich upon reaction vith monodentate aldehydes gave a highly anti-diastereoselective aldol product... 

Titanium enolate aldol reactions have been used in the syntheses of several of important antitumor macrolides and of the immunosuppressive macrolide rapamycin. Duthaler s titanium enolate acetate aldol reaction svas used in the synthesis of epothilone 490. A variety of titanium enolate-based syn aldol reactions highlight the scope and utility of this technique. 

Lewis acid, by enolsilane addition to chiral oxonium ions (cf. equation 40). Oxonium ions are also probably involved in the diastereoselective AlCb-mediated additions of enolsilanes to chiral 2-benzenesulfo-nyl cyclic ethers. In the diastereoselective additions to chiral acetals - (see Section 2.4.4.4), an extension of the methodology shown in Scheme 9 to the enantio differentiation of meso 1,2- and 1,4-diols was reported. An intramolecular Mukaiyama acetal-aldol reaction (see Section 2.4.4.S) was reported as the key step to construct the 11-memboed ring of hydroxyjatrophone A and B. "... 

Scheme 4.35 Solladie-Mioskowski acetate aldol reaction with chiral sulfoxides 168.

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