Ipsenol, synthesis

Diels-Alder reaction of itaconic anhydride with cyclopentadiene yields the adduct (49) which is converted into (50) (Scheme 1) for quantitative retro-Diels-Alder thermolysis to racemic ipsenol (51), reminiscent of the last steps of Mori s ipsenol synthesis (Vol. 6, pp. 18, 19). Both ipsenol (51) and the cor-... 

The first compound (37) is clearly a Diels-Alder adduct and was made this way in a synthesis of Ipsenol. ... 

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. 

As is indicated in Fig. 22-3, the same intermediate cation can yield a variety of end products. For example, pure geranyl diphosphate pinene cyclase catalyzes formation of several other terpenes in addition to a-pinene.89 Another aspect of terpene synthesis is that insects may convert a plant terpene into new compounds for their own use. For example, myrcene, which is present in pine trees, is converted by bark beetles to ipsenol (Fig. 22-3), a compound that acts as an aggregation pheromone.90... 

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). 

Proline-catalyzed direct aldol reactions have also been employed in the context of natural products synthesis, as is illustrated in the synthesis of the bark beetle pheromone (S)-ipsenol of Scheme 4 [16d],... 

Scheme 4. Synthesis of (S)-ipsenol using the proline-catalyzed direct aldol addition reaction as key transformation, (a) L-Proline (10-20mol%), acetone (solvent), 3-7days, 34% (73% ee). (b) TBSCI, imidazole ...

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. 

The ready availability of both enantiomers of (1) has greatly enhanced its value as a synthetic intermediate. The pheromone (S)-(—)-ipsenol (2), prepared in 16% overall yield in four steps from (/ )-( ), is just one of many examples of this utility. In practice, either isomer can sometimes be used by adjusting the order of addition of the groups at C-1 and C-3. The synthesis of (—)-anisomycin (3) illustrates this point. ... 

Figure 4.64 Synthesis of the enantiomers of ipsenol (1). Modified by permission of Shokabo Publishing Co., Ltd...

Concurrent metallation and 1,4-debromination occur when 2-bromomethyl-l,4-dibromo-2-butene is treated with zinc. The resulting species is an isoprenylating agent, which may be applied to the synthesis of ipsenol and ipsdienol. A more active zinc metal for this purpose can be produced by electrolysis." ... 

---