Acyclic stereoselective synthesis

The (diastereoselective) conjugate addition of silylcuprate reagents to a variety of chiral derivatives of a,(3-unsaturated carboxylic acids can be used to prepare optically active p-silyl esters.258 259 Best results are obtained with substrates of type (25). The (related) p-silyl ketones, which also constitute valuable building blocks for (acyclic) stereoselective synthesis, are now accessible in high ee via palladium-catalyzed enantioselective 1,4-disiiylation of a,p-unsaturated ketones (Scheme 76).260... 

The synthesis of branched-chain sugars has been reviewed, and another review on acyclic stereoselective synthesis of carbohydrates Includes references to branched-chain sugars. 

Alditol examples have been included in an extensive review on the acyclic stereoselective synthesis of carbohydrates from non-... 

Scheme 3.60 (l)-Aspartic acid in acyclic stereoselective synthesis. Synthetic studies on... 

Several factors must be considered in selecting a crotyl metal or allyl metal reagent for use in an acyclic stereoselective synthesis. First, it is necessary that the new stereocenters generated in concert with the new C—C bond (Scheme 1) be formed with a high degree of stereoselectivity. This is the problem of simple diastereoselectivity. Two diastereomeric products may be produced, and in this chapter Masa-mune s synlanti nomenclature system will be used to describe them. Second, the issue of diastereofacial selectivity is encountered if the aldehyde (or other C=X reaction partner) is chiral. This is a problem of relative diastereoselectivity, and four products may be produced in the reactions of the crotyl oiganome-tallics (Scheme 2). The diastereofacial selectivity issue is also critical in the reactions of allyl metal reagents and chiral C=X electrophiles. 

It would be difficult to overestimate the role that the polyether antibiotics have played in the development of organic synthesis, particularly in the area of acyclic stereocontrol. These molecules have inspired many spectacular achievements in organic synthesis, achievements that have dramatically expanded the power and scope of the science. In fact, it would not be inaccurate to attribute much of our understanding about the factors controlling acyclic stereoselectivity for such fundamental processes as hydroboration,5 epox-... 

In contrast to the 2-butenylboranes, 2-butcnylboronates have found widespread application in acyclic diastereoselective synthesis owing to their ease of preparation (Section 1.3.3.3.3.1.1.), configurational stability and highly stereoselective reactions with aldehydes3 4. The results of reactions of substituted allylboronates and representative achiral aldehydes are summarized in Table 1. 

It has been established that the course of the sequential pericyclic reaction of cyclopentadienones with acyclic conjugated alkadienes depends on the reaction temperature, thermal treatment at low temperatures affording 3a,4,7,7a-tetrahydroinden-l-one derivatives by way of a Cope rearrangement (see Scheme 38). Roman et al have developed an efficient stereoselective synthesis of enantiomerically pure i-nitrotricyclo[5.2.2.0 ]undeca-3,8-dienes via a tandem consecutive asymmetric Diels-Alder-Cope rearrangement (see Scheme 39). Adducts... 

Acyloxazolidinones of acyclic dicarboxylic acids can be used in the stereoselective synthesis of y-butyrolactones, which has been applied to one of the shortest syntheses of (-)-roccellaric acid (1) reported to date (Scheme 16) [49]. 

Stereoselective Synthesis of Carbohydrates from Acyclic Precursors... 

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. 

This manuscript is based on a lecture presented in the "Stereoselective Synthesis of Carbohydrates from Acyclic Precursors" Symposium at the 194th American Chemical Society National Meeting, New Orleans, September 2,1987. This research is also discussed in Roush, W. R., "Strategies and Tactics in Organic Synthesis," Vol. 2. Lindberg, T., ed. Academic Press New York, 1988. 

The group of K. C. Nicolaou at Scripps Research Institute has developed two synthetic routes to epothilone A. Because the 16-membered lactone ring is quite flexible, it is not likely to impose strong stereoselectivity. Instead, the stereoselective synthesis of epothilone A requires building the correct stereochemistry into acyclic precursors which are closed later in the synthesis. One of the Nicolaou syntheses involves closure of the lactone ring as a late step. This synthesis is shown in Scheme 13.48. Two enantiomerically... 

The authors also investigated the mode of activation of these BINOL-derived catalysts. They proposed an oligomeric structure, in which one Ln-BINOL moiety acts as a Brpnsted base, that deprotonates the hydroperoxide and the other moiety acts as Lewis acid, which activates the enone and controls its orientation towards the oxidant . This model explains the observed chiral amplification effect, that is the ee of the epoxide product exceeds the ee of the catalyst. The stereoselective synthesis of cw-epoxyketones from acyclic cw-enones is difficult due to the tendency of the cw-enones to isomerize to the more stable fraw5-derivatives during the oxidation. In 1998, Shibasaki and coworkers reported that the ytterbium-(f )-3-hydroxymethyl-BINOL system also showed catalytic activity for the oxidation of aliphatic (Z)-enones 129 to cw-epoxides 130 with good yields... 

The rigidity of the allene and its facile formation were imaginatively exploited in a synthesis of the vitamin E side chain alcohol, in which an overall transfer of 1,4 to 1,5 acyclic stereoselection process was achieved (Scheme 8).162... 

The highly stereoselective synthesis of 2,3-fr,ms--3-hydroxytetrahydropyran and 2,3-/ra r-3-hydroxyoxepane was achieved by the Sml2-induced reductive intramolecular cyclization from acyclic compounds having an aldehyde and a /3-alkoxyacrylate fragments <2002CL148>. Based on this reaction, new effective iterative syntheses of trans-fused 6,6,6-tricyclic, 6,7,6-tricyclic, and 6,7,7,6-tetracyclic ethers were developed <2002T1853>. 

Boron trifluoride etherate promotes the fWt/a-selcctivc oxacyclization of polyepoxides derived from various acyclic terpenoid polyalkenes, including geraniol, farnesol, and geranylgeraniol, providing an efficient and stereoselective synthesis of substituted oxepanes and fused polyoxepanes. The oxacyclization transformations may mimic ringforming steps in the biosynthesis of trans-syn-trans-fused polycyclic ether marine natural products <2002JOC2515>. 

Acyclic pentadienyliron complexes show a similar reactivity towards nucleophiles but have found less application so far. Donaldson and coworkers reported an interesting cyclopropanation starting from a pentadienyliron complex (Scheme 1.31) [69]. This procedure has beenused for the stereoselective synthesis of cyclopropylglydnes [70], the preparation of the C9—C16 alkenylcyclopropane segment of ambrutidn [71] and the synthesis of hydrazulenes via divinylcydopropanes [72],... 

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