Chiral auxiliary based approaches group

A chiral auxiliary-based approach has been developed for the preparation of chiral, non-racemic cyclopropyhnethylamines that are not protected with electron-withdrawing groups. The cyclopropanation of ally he tertiary amines bearing a -hydroxide occurred... 

A nice and convergent approach to both compounds makes use of RCM to form the 5-membered building block 71, which mimics the carbohydrate part of the nucleosides. The necessary diene precursor 69 is readily assembled via Evans aldol chemistry. RCM then affords the ring in almost quantitative yield (69->70), leaving the chiral centers and the free hydroxyl group intact. Removal of the chiral auxiliary by reductive cleavage, attachment of the base by means of jt-allylpalladium chemistry, and a final deprotection step complete these highly efficient syntheses [46]. 

Chiral oxazolidinone auxiliaries based on D-glucose were used for aldol reactions by Koell et al. [160]. The highest select vities were observed with auxiliaries equipped with the pivaloyl protecting group. The pivaloylated oxazolidinone 228 was transformed into the boron enolate according to the procedure of Evans [161] and subsequently reacted with aliphatic and aromatic aldehydes. The best results were obtained with isobutyric aldehyde (Scheme 10.77). The syn-dldo 229 was formed in 16-fold excess over the a/i Z-diastereomer and with an acceptable yield of 59%. The authors explain the stereoselectivity by a chair-like transition state according to Zimmermann-Traxler. The electrophile approaches at the less hindered r -face of the (Z)-configured enolate double bond. For A -phenacetyl substituents, an inversed stereoselectivity was observed as described above for these oxazolidinone auxiliaries. 

The first enantioselective total synthesis of (-)-denticulatin A was accomplished by W. Oppolzer. The key step in their approach was based on enantiotopic group differentiation in a meso dialdehyde by an aldol reaction. In the aldol reaction they utilized a bornanesultam chiral auxiliary. The enolization of A/-propionylbornane-10,2-sultam provided the (Z)-borylenolate derivative, which underwent an aldol reaction with the meso dialdehyde to afford the product with high yield and enantiopurity. In the final stages of the synthesis they utilized a second, double-dlastereoditferentiating aldol reaction. Aldol reaction of the (Z)-titanium enolate gave the anf/-Felkin syn product. The stereochemical outcome of the reaction was determined by the a-chiral center in the aldehyde component. 

Based on the letrosynthetic analysis presented above, the first critical task on the way to testing the olefin metathesis-based strategy for the total synthesis of epothilone A (1) was the construction of the three key building blocks 61, 63, and 64. Focusing our attention first on the preparation of aldehyde 64, the Nicolaou group developed several approaches to this building block based on asymmetric synthesis with chiral auxiliaries one of these solutions is detailed in Scheme 19. 

The elimination-addition of AB shown in Figure 5.2c is not limited to intermolec-ular reactions. DKR of racemic 5-hydroxy-2(5H)-furanones and N-acyl-5-hydroxy-2-(5H)-pyrrolinones can be performed by lipase-catalysed enantioselective acylation of the hydroxy groups using vinyl acetate (Scheme 5.36) [109]. This approach has also been extended for the DKR of hemiaminals as shown in Scheme 5.37 [110]. DMAP-based chiral catalyst containing 4-tert-butyl-l,3-thiazoline-2-thione moiety, which was reported as chiral auxiliary of acylation reagent, promotes efficient DKR by asymmetric acylation (Scheme 5.37) [110b]. 

An alternative approach was developed by the group of Demuth97, based on the intermolecular photoaddition of chiral l,3-dioxin-4-ones 192 and 194 possessing the (—)-menthone auxiliary that could smoothly be removed after the photoaddition step. The results of Demuth s pioneering studies into the reactions of chiral dioxinones with cyclic... 

---