Evans syn

The reaction proceeds via the re-side of the enolate and the re-side of the aldehyde 8. The afore mentioned transition state 27 leads to the Evans -syn-aldol product 9 in about 57 % yield and an excellent selectivity of >95 5.6... 

SL2667>. Asymmetric aldol reactions with, V-phenylselanylacetylthiazolidin-2-thione 134 have also been conducted <07S719>. Addition of various aldehydes to the enolate solution of 134 leads to aldol products 135 with excellent selectivity (dr > 96/4) for the Evans syn isomer. 

Enolates derived from a-haloimides also exhibit metal-dependent syn/anti-d do diastereoselection. The derived Li, Sn, and Zn enolates afford the anti isomer in reactions with aromatic aldehydes, while the corresponding B and Sn enolates lead to the conventional syn products. The non-Evans syn adducts... 

The utility of thiazolidinethione chiral auxiliaries in asymmetric aldol reactions is amply demonstrated in a recent enantioselective synthesis of apoptolidinone. This synthesis features three thiazolidinethione propionate aldol reactions for controlling the configuration of 6 of 12 stereogenio centers <05JA13810>. For example, addition of aldehyde 146 to the enolate solution of A -propionyl thiazolidinethione 145 produces aldol product 147 with excellent selectivity (>98 2) for the Evans syn isomer. Compound 145 also undergoes diastereoselective aldol addition with bisaryl aldehyde 148 to give the Evans syn product 149, which is converted to eupomatilone-6 in 6 steps <05JOC9658>. 

Asymmetric aldol reactionsThe enolate of the N-propionyl derivative of 1 can undergo highly syn-selcctivc aldol reactions to provide the non-Evans syn-aldols (16, 48). 

As the role of the common precursor 34 is critical, it has been synthesized in large scale by using an Evans syn aldol protocol [39], starting from the commercially available (i )-(-)-methyl 3-hydroxy-2-methyl propionate 1 . This compound was transformed in three steps to aldehyde 32 [40, 41] and used in an Evans aldol reaction with the dibutylboron enolate A. The Weinreb amide formation completed the construction of the common precursor 34 [42] (Scheme 7). From this precursor fragments C1-C8, C9-C14 and C15-C21 were synthesized (Scheme 8). 

Within this sequence (Scheme 5) two of the reactions turned out to be really problematic, the Evans syn aldol and the reductive removal of the oxazolidinone to generate alcohol 30. 

Boron-mediated asymmetric aldol condensation methodology developed by Evans [90] served as an inspiration for preparation of daunosamine starting from chiral oxazoUdinones. It appeared that the choice of chiral auxiUary is quite important for the stereochemical outcome of planned reactions [91]. A successful series of reactions started from N -succinoylation of (R)-3-(l-oxo-3-carbomethoxypropyl)-4-diphenylmethyl)oxazolidin-2-one as a novel chiral auxihary. The chain extension was achieved in aldol condensation with protected lactaldehyde and the key intermediate 132 was converted into the target aminosugar 135, via Curtius rearrangement of carboxyhc acid azide, and reduction of lactone to lactol, as depicted in Scheme 24 [58]. Unexpectedly, boron catalysts were rather ineffective in the aldol condensation step and had to be replaced with more reactive lithiiun enolates (which proved to be non-Evans syn selective). 

Titanium(IV) enolates of oxazolidinethiones have beenrecently popularized as a result of the observation that the titanium(TV) enolates (eq 9), much like the tin (II) enolates, can provide the non-Evans syn- Ado adducts. ... 

Further development of this observation led to the discovery that the readily available titanium(IV) enolate of )V-propionyl-4-benzyloxazolidine-2-thione can lead to either the non-Evans syn-or the Evans sjn-aldol adducts hy virtue of properly controlling the reaction conditions. Exposure of AApropionyl-4-henzyloxazoli-dine-2-thione to 2 equiv of titanium(I V) chloride and diisopropylethylamine followed hy the addition of aldehyde produced the non-Evans sj -product preferentially (eq 10), while the treatment with 1 equiv of titanium(IV) chloride and 2.2 equiv of (—)-sparteine produced the Evans s//j-product as the major dia-stereomer (eq 11). These results led to a proposed model of switching between the chelated and non-chelated transition states. 

The boron-mediated aldol reaction of an Evans s acyl oxazolidinone with an aldehyde affords the Evans-syn aldol adduct 9. The process proceeds via formation of the Z enolate that reacts with the aldehyde, presumably through a well ordered six-membered, chair-shaped Zimmerman-Traxler model... 

A proposed highly ordered chelated transition states for aldol additions using titanium enolates of thiazolidinethiones has been proposed by Crimmins. Crimmins s thiazoldinethione aldol proceeds with high diasteroselectivity for the Evans or non-Evans syn-product depending on the stoichiometry of the Lewis acid as well as the nature and amount of the... 

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. ... 

In the first formal asymmetric synthesis of phorbol, a tigliane diterpene, Wender and co-workers utilized a chiral oxazolidinone-based asymmetric aldol reaction to produce chiral alcohol 43, a non-Evans syn product as a single diastereomer in 96% yield. ... 

Two Evans aldol reactions were used to create the C5 and Cl stereocenters in the asymmetric synthesis of a Taxol C-ring with chloroacetyl oxazolidinone 33, giving the Evans syn-aldol 45 as a single diastereomer in 77% yield. ... 

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