Acyclic Diastereoselective Approaches

The synthesis of aldehyde 48 proceeds in 16 steps from (S)-39 in 15% yield and 75% stereoselectivity. The brevity, efficiency, and selectivity of this synthesis rivals alternative acyclic diastereoselective approaches to the rifamycin ansa chain, (see footnote 4 in reference 3i), thereby providing a clear testimony to the potential of the tartrate allylboronates as reagents for complex synthetic problems. 

Over the past two decades, chiral allyl- and crotyl-boron reagents have proved to be extremely valuable in the context of acyclic stereoselection. The development of superior allyl-boron reagents, which can give enantio- and diastereoselectivities approaching 100%, has become both challenging and desirable.68... 

Facing the challenge of synthesizing the antibiotic erythromycin A la, Woodward s group took advantage of a cyclic system to achieve diastereofacial selectivity, the so-called cyclic approach.3 This approach was taken to deal with the common problem of low diastereoselectivity associated with acyclic substances. 

The stereoselective synthesis of carbohydrates from acyclic precursors is a research topic that has attracted considerable attention over the past decadeT Efforts in this area are easily justified and have maximum impact particularly when directed toward rare sugars or other polyhydroxylated molecules that are not conveniently accessed via classical "chiron" approaches.2 An underlying theme of such efforts, of course, is the development of practical synthetic methodology that will find broad application in the enantio- and diastereoselective synthesis of natural products, their analogues, and other compounds of biological interest. 

As with acyclic dienes, methods have been developed for enantioselective and diastereoselective complexation of prochiral and chiral cyclic dienes. An approach has been developed for the asymmetric catalytic complexation of prochiral eyelohexa-1,3-dienes nsing (1) in the presence of catalytic amounts of l-azabuta-l,3-dienes such as (232) or (233) an enantiomeric excess as high as 86% has been reported. By contrast, attempts to effect diastereoselective complexations using cyclic diene systems eqnipped with chiral auxiliaries have met with limited success. On the other hand, direct complexation of chiral cyclic dienes snch as (234) and (235) proceed with a high degree of diastereoselectivity, where the iron tricarbonyl fragment is directed syn to alcohols or ethers by transient coordination ( heteroatom dehvery ) (Scheme 66). ... 

The second approach to achieve asymmetric induction used (-)-(li ,3f ,45)-menthol or ( —)-(l/C3/C4S)-8-phenylmenthol as chiral auxiliary in diazenes 13 (Table 2, entries 10 and ll)23. In no case was the induced diastereoselectivity higher than a diastereomeric ratio of 53 47 and thus this route did not prove to be synthetically useful. Obviously, the auxiliary at the end of the tether plays no significant role in determining the direction of coiling of the acyclic chain 23. 

In a related approach, Chercheja and Eilbracht [19] examined cyclic olefins together with acyclic and cyclic ketones (Scheme 5.130). Instead of monoden-tate phosphines as ligands, P(OPh)3 was used for the hydroformylation step. In general, the diastereoselectivities with cyclic substrates and reagents, respectively, were lower than those observed in the reaction of acyclic olefins and aldehydes by the Breit group (compare Scheme 5.129). 

The use of an auxiliary of a,P-unsaturated compound in the cycloaddilion reaction of acyclic nitrone improves the yield and diastereoselectivity of product. Moreover, the use of bulky catalyst favors the cxo-selectivity of the product. For example, N-crotonoyl succinimide 133 reacts with C,N-diphenyl nitrone 127 in toluene at rt to give exclusively cndo-product 135, whereas in the presence of 5 mol% of TiCl2-TADDOLate 134 in toluene gives exclusively exo-product 136 with high (73 %) ee. The X-ray study of the TS indicates that the nitrone approaches the alkene from an Re face to give the exo-product [111]. 

Diastereoselective silacyclopropanation of 5-e rfo-substituted norhomene 13 and 1,1-disusbtituted alkenes 14 and 15 by lithium reduction of f-Bu2SiCl2 was also reported (Table 1). In the case of norhomene 13, the selectivity arises due to exo-approach of the silylene intermediate to the olefin. However, in case of 1,1-disubstituted alkenes, minimization of 1,2-allylic strain accounts for the observed acyclic stereocontrol. S)uithetic utility of such diastereoselective silacyclopropanation was also demonstrated hy... 

In 1973, Mukaiyama and his co-workers reported the use of silyl enol ethers as ketone enolate equivalents. Silyl enol ethers react with aldehydes in the presence of a stoichiometric amount of TiCU as a Lewis acid (Scheme 3-78). The Lewis acid is considered to electrophilically activate aldehydes. Since this landmark discovery, many efforts have been made to improve the original protocol, especially focusing on the use of a catalytic amount of Lewis acid catalysts.A wide variety of metal complexes and nonmetallic cationic compounds is now applicable to this reaction as a catalyst. Not only aldehydes but also acetals, ketones, and imines have been extensively employed as electrophiles for the aldol reactions. The reaction generally proceeds via an acyclic transition state, in which the electron-rich double bond of enol silyl ethers approach carbonyls activated by a Lewis acid (Scheme 3-79). In most cases, acyclic transition state with an antiperiplanar orientation of reactants well accounts for observed diastereoselectivities. ... 

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