Stereoselective synthesis from acyclic

SCHMIDT Stereoselective Synthesis from Acyclic Precursors... 

Boron triflates 45a and 45b are very useful chiral auxiliaries. Boron azaenolate derived from achiral35 and chiral36 oxazolines gives good stereoselectivity in the synthesis of acyclic aldol products, particularly for the rarely reached threo-isomers. By changing the chiral auxiliary, the stereochemistry of the reaction can be altered.37... 

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 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 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],... 

The stereocontrol inherent in the totally regiospecific 5-exo-trig isomerizations of substituted 5-hexenyllithiums may be exploited for the stereoselective synthesis of bicyclic systems by tandem cyclization of acyclic diolefinic alkyllithiums. To date, this strategy has not been widely applied, and the first examples were reported by Bailey and Rossi who were able to cyclize the organolithiums derived from iodides 113 and 115 in the presence of TMEDA to afford the polycarbocyclic products 114 and 116 (Scheme 33)61. 

An example of the utilization of a bridged bicyclic ketone for preparation of an acyclic moiety is the stereoselective synthesis of the C-21 to C-27 segment of rifamycin-S, a member of the ansamycin family of antibiotics (Scheme 18). Rao et alP used ketone (61), derived from furan, to prepare lactone (62). Exhaustive reduction of (62) provided the segment (63), which contains five chiral centers of lifamycin-S. 

From these examples it is clear that the principles of acyclic stereocontrol that govern the allylation reactions of achiral Type II allyl- and crotylmetal reagents with chiral aldehydes can be used to excellent advantage in the stereoselective synthesis of natural products. In the following section, the factors that influence the stereoselective formation of cyclic compounds in the ring-closing allylation reaction are discussed and selected synthetic applications are reviewed. 

Alkylidenation-intramolecular insertion. A stereoselective synthesis of cyclo-pentenes from acyclic ketones occurs by reaction of the latter with lithio-trimethylsilyldiazomethane. An application of this method to the synthesis of (+)-cassiol and oxo-T-cadinoP attests to its usefulness. 

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

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