Ipsenol chiral

A number of new and asymmetric syntheses of (S)-(-)-ipsenol (34) and (S)-(+)-ipsdienol (35), the pheromone of Ips bark beetles, were reported. Scheme 49 summarizes the synthesis of ipsenol by Riedeker and Steiner [75], which enabled them to prepare 56 g of (S)-34. They employed chiral auxiliary B derived from D-glucose. 

Chiral allenylboronic esters.1 The enantioselectivity in synthesis of homo-propargylic esters by the reaction of aldehydes with chiral allenylboronic esters (11, 181) is markedly increased by use of bis-2,4-dimethyl-3-pentyl esters of d- or vAaxtaric acid rather than the diethyl ester. Yields in the reaction of various saturated aldehydes are 70-90%, and optical yields are consistently greater than 90% and even higher (97-99%) when the aldehyde is present in excess. However, yields are poor in reactions with aryl and a,p-unsaturated aldehydes. This modified procedure was used in a synthesis of (S)-(—)-ipsenol (2) from d-(—)-bis(2,4-di-methyl-3-pentyl) tartrate (1) (equation I). 

Chemical shift nonequivalence of the methyl groups of an isopropyl moiety near a chiral center is frequently observed the effect has been measured through as many as seven bonds between the chiral center and the methyl protons. The methyl groups in the terpene alcohol, 2-methyl-6-methylen-7-octen-4-ol (ipsenol) are not chemical shift equivalent (Figure 3.55). They are diastereotopic, so a strong magnetic field is usually necessary to avoid superposition. 

Most asymmetric syntheses require rather more than one or two steps from chiral pool constituents. Male bark beetles of the genus Ips produce a pheromone that is a mixture of several enantiomerically pure compounds. One is a simple diene alcohol (S)-(-)-ipsenol. Japanese chemists in the 1970s noted the similarity of part of the structure of ipsenol (in black) to the widely available amino acid (S)-leucine and decided to exploit this in a chiral pool synthesis, using the stereogenic centre (green ring) of leucine to provide the stereogenic centre of ipsenol. 

Oertle, K., Beyeler, H., Duthaler, R.O., et al. 1990. A facile synthesis of optically pure (-)-(S)-Ipsenol using a chiral titanium complex. Helvetica ChimicaActa, 73 353-58. 

Brown, H. C., Randad, R. S. B-2 -lsoprenyldiisopinocampheylborane an efficient reagent for the chiral isoprenylation of aldehydes. A convenient route to both enantiomers of ipsenol and ipsdienol. Tetrahedron Lett. 1990, 31,455-458. 

The chiral GCxGC-TOFMS analyses of bark beetle samples showed clearly the advantage of the comprehensive two dimensional gas chromatography - all obtained data were easily interpreted and results showed the strong enantioselectivity in the pheromone component composition, especially in ipsenol (1) and cis-verbenol (3). We found practically only (S)-l and high excess (>1 10) of (lS)-3 in both species, in contrast to frfljjs-verbenol (4) which was in examined samples present mostly only in racemic form Racemic ipsdienol (2) we found in I, nitidus and predominantly as (R)-isomer in I. shangrila. 

Ikeda, N. Aral, L Yamamoto, H. 1986. Chiral allenylboronic esters as practical reagents for enantioselective carbon-carbon bond formation. Facile synthesis of (-)-ipsenol. J. Am. Chem. Soc. 108 483-486. 

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