Ring diastereoselectivity

Alcaide and Almendros have developed a novel palladium-catalyzed domino heterocyclization/cross-coupling reaction of various a-allenols and MBH acetates, furnishing [(2,5-dihydrofuran-3-yl)methyl]acrylate derivatives 489 and 490 and the acrylonitrile 491 in moderate to good yields (Scheme 3.216). " Ozonolysis of MBH adducts originating from aromatic aldehydes provides a-ketoesters 492 with different substitution patterns on the aromatic ring. Diastereoselective reduction of the a-ketoesters 492 affords the corresponding a,p-dihydroxy-esters 493 with excellent anti diastereoselectivity. This method provides an alternative approach for the synthesis of either a-ketoesters or a,p-dihydroxy esters (Scheme 3.217). ... 

Using dioxolane as a substituent in the 1,3-dipolar cycloaddition of diazomethane with olefinic double bonds, it was found that the bulky dioxolane ring plays a major role in the diastereoselection [OOJOC388]. 

The initial investigation focused on the use of threitol-derived auxiliaries with various substituent groups on the dioxolane ring (Table 3.3). However, it became evident that the oxygen atoms in the substituents had a detrimental effect on selectivity. Comparison of the diastereoselectivities for the ketals 69-71, which contain Lewis basic sites in the substituents at the 1 and 2 positions, with those from simpler diol derived ketals 72-74 demonstrates the conflicting effects of numerous coordination sites. The simpler, diol-derived ketals provide superior results compared to the threitol derived ketals. The highest diastereoselectivity is observed in the case of the 1,2-diphenyl ethane-1,2-diol derived ketal 74. 

Lewis acids, results in the formation of isopulegol (43) with greater than 98% diastereoselectivity isopulegol (43), wherein all of the ring substituents are equatorially oriented, arises naturally from a chairlike transition state structure in which the C-3 methyl group, the coordinated C-l aldehyde carbonyl, and the A6,7 double bond are all equatorial (see 48). A low-temperature crystallization raises the chemical and enantiomeric purity of isopulegol (43) close to 100%. Finally, hydrogenation of the double bond in 43 completes the synthesis of (-)-menthol (1). 

In an effort to make productive use of the undesired C-13 epimer, 100-/ , a process was developed to convert it into the desired isomer 100. To this end, reaction of the lactone enolate derived from 100-) with phenylselenenyl bromide produces an a-selenated lactone which can subsequently be converted to a,) -unsaturated lactone 148 through oxidative syn elimination (91 % overall yield). Interestingly, when 148 is treated sequentially with lithium bis(trimethylsilyl)amide and methanol, the double bond of the unsaturated lactone is shifted, the lactone ring is cleaved, and ) ,y-unsaturated methyl ester alcohol 149 is formed in 94% yield. In light of the constitution of compound 149, we were hopeful that a hydroxyl-directed hydrogenation52 of the trisubstituted double bond might proceed diastereoselectively in the desired direction In the event, however, hydrogenation of 149 in the presence of [Ir(COD)(py)P(Cy)3](PF6)53 produces an equimolar mixture of C-13 epimers in 80 % yield. Sequential methyl ester saponification and lactonization reactions then furnish a separable 1 1 mixture of lactones 100 and 100-) (72% overall yield from 149). 

More recently, Davis and co-workers developed a new method for the asymmetric syntheses of aziridine-2-carboxylates through the use of an aza-Darzens-type reaction between sulfinimines (N-sulfinyl imines) and a-haloenolates [62-66]. The reaction is highly efficient, affording cis- N-sulfmylaziridine-2-carboxylic esters in high yield and diastereoselectivity. This method has been used to prepare a variety of aziridines with diverse ring and nitrogen substituents. As an example, treatment of sulfinimine (Ss)-55 (Scheme 3.18) with the lithium enolate of tert-butyl bromoacetate gave aziridine 56 in 82% isolated yield [66],... 

The regioselective ring-opening of vinyloxiranes by nitrogen nucleophiles offers an attractive route to vie-amino alcohols, compounds of much recent interest. As with oxygen nucleophiles, the stereochemistry of the reaction can be controlled by choice of reaction conditions aminolysis of 25, for example, affords anti-amino alcohol 26 in excellent yield and diastereoselectivity (Scheme 9.21) [48, 96, 97], and... 

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