Homoallyl alcoholsUsing 1,2-dicyclohexyl-1,2-ethanediol as chiral auxiliary, the enantiomerically pure 2-pentenylboronate 9c was obtained. Its addition to benzaldehyde proceeded with complete transfer of chirality to give the syn-E-homoallyl alcohol 11. The ability of the reagent 9c to create new stereocenters under reagent control of diastereoselectivity was tested in its addition to the chiral aldehydes 15 and 24. This resulted in a short and stereospecific synthesis of invictolide (18), as well as of a C-9/C-15-partial structure 25 of erythronolide A.One strategy for the synthesis of natural products of polyketide-derived biogenesis, especially for the synthesis of polypropionate molecules2), consists in an iterative sequence of chain elongation steps.Stereoselektive Syntbese von Alkoholen, XXXI'? -Stereosdektive C-C-Bindungsbildung mit Hilfe chirakr Z-Pentenylboro&4uter Unter Verwendung von 1,2-Dicyclohexyl-l,2-ethandiol als chiralem Auxiliar wurde der enantiomerenreine Z-Pentenylboronsaureester 9c erhalten. Dessen Addition an Benzaldehyd ergab den syn-E-Homoallylalkohol 11 unter vollstandiger ChiralitatsObertragung. Die Fihigkeit des Reagenz 9c zur Bildung neuer Stereozentren unter Reagenz-Kontrolle der Diastereoselektivitat wurde in der Addition an die chiralen Aldehyde 15 und 24 gepruft. Dies fiihrte zu einer kurzen stereospezifischen Synthese des Invictolids (18) wie der eines C-9/C-15-Bausteins 25 des Erythronolids A.Control of the formation of the individual stereocenters depends on simple diastereoselection during the carboncarbon bond forming steps3) as well as on reagent control of diastereo~electivity~) using chiral reagents exerting high asymmetric induction. We recently reported on cr-methoxy-(E)-crotylboronates (1) as reagents, which allow for the generation of the stereotriades C and D'). Here, we would like to describe the chiral 2-pentenylboronate 2, which should allow for the generation of the stereotriades A and B. Some aspects of this work have already been communicated in preliminary form ' 1.A preceding study on racemic E-and Z-pentenylboronates') demonstrated that only the Z isomer 3 shows high diastereoselectivity on addition to aldehydes. The product 4 with an E-double bond is formed preferentially since the transition state 5 of the competing reaction leading to 6 with a 2-double bond is destabilized by allylic 1,3-strain6). As the Chem.
Pentenylboronates, either > 90% 2 (4) or > 95% E (3), can be obtained by reaction of the pentenyl Grignard reagent with different borates. The 2-pentenylboronates 4 add to aldehydes under high simple diastereoselection to give the diastereomerically pure syn-homoallyl alcohols 10. The corresponding addition of the E-.pentenylboronates leads to the anti-homoallyl alcohols as E-(lJ)/ 2417) mixtures.Stereogenic carbon -carbon bond forming reactions are of prime interest in stereoselective synthesis*). A wellestablished3) reaction is the addition of E-and Z-crotylb o r o n a t e~~~~) such as 1, or of E-and Z-crotylboranes') to aldehydes, a reaction which proceeds with high simple diastereoselection.These reagents are in general prepared by deprotonation of E-or Z-butene to E-or Z-butenylpotassium') followed Stereoselektive Syntbese von Alkoholen, XXX '? -E-und 2-Pentenylboronsiiuter, Reagenzien, die sich onter einfacher Diastereoselektivit&t an Aldehyde addieren Durch Reaktion des Pentenyl-Grignard-Reagenzes 2 mit verschiedenen Borslureestern erhalt man Pentenylboronslureester entweder zu >90% als Z-Isomer 4 oder zu >95% als E-Isomer 3. A#-dition der 2-Pentenylboronsaureester 4 an Aldehyde ergibt die 'diastereomerenreinen syn-Homoallylalkohole 10. Entsprechende Addition des E-Pentenylboronsauresters 3 fiirt zu anti-Homoallylalkoholen als E-( 15)/2-(17)-Gernische.by borylation. The generation of butenylpotassium does not lend itself to scale up readily. Of the other routes to such crotylboron compound^^.'^) some require separation of geometric isomers of a precursor [E/Z-1 -bromopropene"' or E/Z-crotylbis(dimethylamino)boranes4~] in a spinning band column. As long as only simple diastereoselection on addition to aldehydes is concerned, the E-and Z-pentenylboronates 3 and 4 might do as well. The E reagent 3 can easily be prepared in a diastereomeric purity of >95% by reaction of the simple pentadienyl Grignard reagent 2 with triisopropylborate") and this has been achieved on a scale of up to 0.36 mole. However, for adhtion to aldehydes the crude product had to be used, since 3 has a tendency to decompose to a solid material on distillation (polymerisation?).Further experiments showed that the 3/4 ratio depends on the borylating agent. Representative results are given in Scheme 1.
The preparation of 6-ethyl-4.hydro~-3,5-dimethyl-2-pyrone (5) has been h p v d Selective functionalizatioa in the 6-a position of the pyrone 5 was possible by converting it into the k t o x y compound 11 followed by selenium dioxide oxidation to the dcoho1 13. Tbe latter could be oxidized to the ketone 17 or be converted via the bromide 12 kt0 other 2-pyr0ne.s having a hetera rubstituent in the 6-a position.Persubstituted 4-hydroxy-or 4-methoxy-2-pyrones 1 or 3 and persubstituted 2-methoxy-4-pyrones 2 are partial structures common to many polyketide-derived natural products. The side chain at C-6 may be attached via an olefinic carbon'), or a tertiary carbon center2). Occasionally an epoxide ring is adjacent to the pyrone nucleus3). Among the most simple representatives are the pyrone 3, isolated from Helichrysum callicomum4), or nectriapyrone') (4). In contrast to the abundance of these structures in nature, there are rather ways recorded to synthesize such highly substituted pyrones. Most syntheses use a de novo preparation of the pyrone ring from P,G-diketocarboxylates'). The alternative, to use a simple pyrone such as 5 as a starting point for further elaboration, therefore seems attractive. This requires that 5 can be selectively functionalized at the 6-a position to give such pyrones as 6 or 7. We describe here our efforts along these lines. The starting material 5 has been known for a long time') under a different structure"). Since the preparation of 5 as To this end the diketone 8") was converted into the dianionf2), and this was carboxylated to yield the thermally labile (< 30°C) P,G-diketo acid 9 which was dehydrated by the action of acetic anhydride at room temperature to give 77% of the desired pyrone 5.Since the 6-a-bromination of 4-hydroxy-6-methyl-2-pyrone can be achieved by N-bromosuccinimide (NBS) in refluxing CC1413), we subjected 5 to these conditions. This, however, gave rise to the formation of the bromolactone 10 (ca. 90%).
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