Improved synthesis of optically active ipsdienol

Abstract

SHORT COMMUNICATIONSIn our preceding publication [1] a simple procedure was described for the preparation of both enantiomers of monoterpene alcohol ipsdienol 1, an actual pheromone component of bark beetle of genus Ips. The key synthesis stage was the resolution of the direct precursor of the ipsdienol, (±)-6-methyl-2-(2-chloroethyl)hepta-1,5-dien-4-ol by its conversion into acid phthalate and the crystallization of the acid phthalate as salt with (+)-or (-)-1-phenylethylamine. Then the optically active acid phthalates (S)-2 and (R)-2 were treated with potassium tert-butylate in tertbutyl alcohol. By the dehydrochlorination and the simultaneous alcoholysis of the ester moiety in one stage (S)-or (R)-ipsdienol was obtained in a 55% yield.The necessity of preparation of a large amount of optically active ipsdienol (S)-1 required a detailed study of the reaction between acid phthalate (S)-2 and potassium tert-butylate, since the reaction proceeded with a reproducible yield about 50%. In the initial procedure [1] a large amount of solvent and an essential excess of the base were required. In the reaction mixture a large quantity of unreacted acid phthalate of ipsdienol was present. The increase in the reaction dura-tion from 1 to 3 h and the use of more concentrated 20% solution of potassium tert-butylate not only did not increase the yield of ipsdienol (S)-1, but even resulted in a consi-derable decrease in its enantiomeric purity. In various expe-riments we observed unexpected and undesirable decrease in the enantiomeric excess of ipsdienol (S)-1 to 75-80% (Scheme 1).The heterolysis of esters of the optically active allylic alcohols at the O-R bond ( where R is the residue of the allylic alcohol) and the accompanying rearrangements with the migration of the double bond and the racemization along the S N 1 mechanism are studied in sufficient detail and have been discussed before [2][3][4][5]. These transformations were mostly studied by an example of acid phthalates which were used for resolution of the corresponding allylic alcohols into individual enantiomers. It was established by this research that the heterolysis of esters with the formation of allylic carbocations is sharply accelerated at higher temperature, but the optically active allylic alcohols proper do not suffer

Resolution by diastereomeric salts: Access to both enantiomers of racemic acid using the same enantiomer of resolving base

“…The behavior of diastereomeric salts we observed here is not common according to our experience 1,11–15 and among a huge number of known resolution procedures. Usually, the treatment of racemate with a resolving reagent results in a pair of salts with different solubility (crystallinity).…”

Practical method for increasing optical purity of cis‐verbenol

“…Often, the resolution of enantiomers by crystallization compares favorably with other separation techniques due to better robustness and scalability, and high purity of final products. Following our successful experience, we have chosen this approach toward verbenol. The only known report on the enantioenrichment of cis ‐verbenol was published by Mori in 1976 .…”

Developments in the Catalytic Asymmetric Synthesis of Agrochemicals and Their Synthetic Importance

“…Recently, an efficient asymmetric iridium catalyzed carbonyl (2-vinyl)­allylation or isoprenylation was reported through hydrogen autotransfer or 2-propanol-mediated reductive coupling while reacting primary alcohols and aldehydes, respectively, with isoprenyl tert -butoxy carbonate 136 by Krische et al While employing this approach, enantioselective total synthesis of the terpenoid natural products (+)-ipsenol 129 and (+)-ipsdienol 140 had been achieved (Figure ). − Asymmetric catalytic system, that is, π-allyliridium C,O-benzoate complex ( S )-Ir- 141 (5 mol %) derived from 3,4-dinitrobenzoic acid and ( S )-DM-SEGPHOS was explored for this methodology. The reaction of isoprenyl tert -butoxy carbonate 136 with Isovaleraldehyde 126 and 3-methyl-but-2-enal 137 in the presence of­( S )-Ir- 141 , K 3 PO 4 and 2-propanol as reducing agent gave (+)-ipsenol 129 and (+)-ipsdienol 140 , respectively (Figure ).…”