Die Strukturdynamik von Pentadienylmetall‐Verbindungen mit endständiger Alkyl‐Gruppe: zugleich «stereoselektive» und «stereodefensive» Synthese eines natürlichen Riechstoffes

Abstract

The (2 Z, 4 E)-, (2 E , 4 Z)-and (2 E, 4 E)-isomers of 2,4-decadien-1-01 (5) have been obtained with high and predictable stereochemical homogeneity starting from both (2)-and (E)-1,4-decadiene. These hydrocarbons were hydroxylated in a reaction sequence consisting of metallation (by means of s-butyllithium or butyl-1ithiunVpotassium-t-butoxide, giving rise to organometallic intermediates of specific conformation), dimethoxyborylation and oxidation. The different decadienols as well as (2 E , 4 2)-2,4-undecadien-l-01 were converted into the isovalerates, the ester derived from (2 E , 4 Z)-2,4-decadien-l-ol being a natural flavor component.Allylmetall-Verbindungen treten in zwei bevorrech teten Konformationen auf, der ccendo,) -und der ttexo))-Form 1, die beide dank Koplanaritat grosstmoglichen Mesomenegewinn erzielen. Wahrend lithium-und magnesiumorganische Verbindungen vom Allyl-Typ in Sekundenschnelle das Torsionsgleichgewicht zwischen den ctendow-und ccexo>>-Formen einstellen, sind die entsprechenden Natrium-, Kalium-und Casium-Derivate bemerkenswert konformationsstabil. Ausgehend von (Z)-bzw. (E)-2-Alkenen lassen sie sich gezielt erzeugen. Wird die organometallische Zwischenstufe durch Einwirkung eines Elektrophils (El) hinreichend rasch in das Endprodukt 2 umgewandelt, so findet man die gleiche raumliche Anordnung der Substituenten an der Doppelbindung wieder, wie sie in der Alken-Vorstufe vorgegeben war. Wir sprechen dann von einer ccstereodefensivenw Reaktionsfolge.

Total Synthesis and Biological Evaluation of the Protein Phosphatase 2A Inhibitor Cytostatin and Analogues

“…Partial reduction of diynes has been carried out mainly by hydrogenation with the Lindlar catalyst [20] and zinc reduction. [21] Pent-1-yn-3-ol (11) was protected as p-methoxybenzyl ether 12 (Scheme 1).…”

“…(E)-Crotonic aldehyde (20) was transformed to dibromoalkene 21 following the Corey±Fuchs protocol. [29] Selective reduction to (Z)-bromoalkene 22 and subsequent Sonogashira reaction with alkyne 12 yielded the desired dienyne 23.…”

Pentadienyl Type Lithium and Potassium Species: The Regioselectivity of their Reactions with Electrophiles

“…We wanted to include in the present study also "5-methyl-2,4-pentadienylmetals" (2,4-hexadienylmetals) which we expected to show, qualitatively at least, the same stereochemical dynamics and preferences as already reported for 2,4-decadienylmetals. 7 This was indeed found to be the case. For well intelligible reasons, 7,18 the internal double bond retained the configuration inherited from its hydrocarbon precursor and the organometallic intermediate generated upon deprotonation with sec-butyllithium adopted the "W-form".…”

“…5,6 The conformational population of pentadienyls carrying a primary alkyl chain at the 1-position again depends on the nature of the metal and the solvent. 7 In contrast, all 3-methyl-2,4-pentadienyls 4,8 exist in the "W-shape" and all 2,4-dimethyl-2,4pentadienyl 4 in the "U-shape" regardless whether combined with lithium or potassium and dissolved in tetrahydrofuran or suspended in hexanes. The third privileged structure, the equally coplanar and hence again optimally resonance-stabilized "S-form" has so far been identified only in mobility-restricted cyclic structures.…”

“…The stereopreferences of pentadienyl-type organometallics were probed either by NMR spectroscopy 2,3,6,8 or by correlation of the stereocomposition of the reactive intermediates with that of their final, isolable products. 4,5,7,9,10 The latter approach relies on the availability of "well-behaved" electrophiles, such as silanes or boranes, which attack preferentially or exclusively terminal positions of the delocalized area. If, on the contrary, the electrophile becomes attached to the central carbon atom, most if not all stereochemical information inherent in the organometallic intermediate gets lost.…”