S-Citronellate

During work-up of the products of ozonolysis of R- and S-citronellic acids, a substantial quantity of the highly explosive trimeric acetone peroxide (3,3,6,6,9,9-hexamethyl-l,2,4,5,7,8-hexoxonane) was unwittingly isolated by distillation at 105-135°C to give the solid m.p. 95°C. The peroxide appears to have been produced by ozonolysis of the isopropylidene group in citronellic acid, and presumably the same could occur when any isopropylidene group is ozonised. Appropriate care is advised. 

S )-citronellal 42 can also be prepared similarly from 40. Asymmetric hydrogenation of (R)-43 provides 44, which can be used to make the side chain of vitamins E and K (Scheme 6-22). 

R,S)-Citronellal can be purchased from BASF, and (R)-citronellal from Dragoco, Fluka, or Takasgo Perfumery Co., Ltd., Japan. (R)-Citronellal can also be synthesized from pulegone with ee >99%.5 (S)-Citronellal may be obtained by oxidation of (S)-citronellol,6 which is accessible by different routes with ee 95%.7 The optical purity of citronellal can be determined by GLC after conversion to the acetal of (-)-(2R,4R)-pentanediol.8 For the reactions described, (R,S)-citronellal from BASF, (R)-citronellal from Dragoco, and (S)-citronellol from Fluka were used. (R,S)-Citronellal... 

BINAP [(2,2 -diphenylphosphino)-1,1 -binaphthyl] is the best among the various chiral diphosphines which were tried. The same complex isomerizes N,N-neryldiethylamine to S-citronellal enamine. 

This asymmetric Michael addition was used for synthesis of (S)-citronellic acid (6) from the chiral crotonate 5 and a 4-methyl-3-pentenylcopper reagent. 

With the catalysts derived from (S,S)-l,2-bis(diphenylphosphinomethyl)cyclobutane and [RhH(CO)(PPh3)3] or rhodium carbonyls, the a,3-unsaturated aldehydes, neral and geranial, are hydrogenated to (E)- and (S)-citronellal in 79% and 60% ee, respectively. Cyclic a,3-unsaturated ketones such as isophorone and 2-methyl-2-cyclohexenone have been hydrogenated using ruthenium hydrides coordinated with chiral diphosphines in up to 62% ee to give chiral ketones, though conversions are not satisfactory. ... 

In the diterpene series a notable recent example of semisynthesis is that (ref.24) of pachiclavularolide (28) a substance isolated from the soft coral, Pachiclavularia violacea. starting from S-citronellal readily available from S-citronellol. The key step in the formation of the macrocycle is an intramolecular palladium-catalysed diyne cyclisation following initially a Mislow-Evans rearrangement of a sulphinyl ester from S-citronellal. ... 

Oppolzer has developed a method of asymmetric synthesis based on the use of the chiral auxiliaries 39A and 39B derived respectively from (+ )-camphor [(+ )-40] and (- )-camphor [(- )-40]. Crotonylation of 39A gave the ester that was attacked by 4-methyl-3-pentenyllithium in the presence of copper iodide tributylphosphine and boron trifluoride from only one side of the molecule, the product 41 having the (S)-configuration (enantioselectivity 98.5%). The ester 42—similarly obtainable from 39B—was methylated under similar conditions, also yielding 41 with 92% enantioselectivity. (S)-Citronellic acid [(S)-36] or (S)-citronellol [(S)-33] were then obtained from 41 by the action of sodium hydroxide or lithium aluminum hydride (Scheme 6). Reduction of potassium... 

The chiral source for our synthesis of (+)-52 was methyl (.S )-citronellate, which was converted to acetylenic phenylselenyl ester A. Radical-mediated cyclization of A afforded B. Further conversion of B to C was followed by its reduction and lactonization to give lactones D and E. Formylation of D gave F, which was coupled with bromolactone ( )-G to give (-l-)-sorgolactone (52) and its diastereomer 52. Similarly, E yielded two additional diastereomers, 52" and 52". ... 

S)-Diester E prepared from (.S )-citronellal was cyclized under the Dieckmann conditions to give (S)-F. Its hydrolysis and decarboxylation were followed by methylation to furnish (S)-G, whose Robinson annu-lation yielded (-)-A (= 81 ). The structure of the crystalline ketone (-)-A was solved by X-ray analysis, and then (-)-A was further converted to (-)-B, (-)-C and (—)-D. Although C (= 83 ) and D (= 84 ) possess the absolute configuration given to the dextrorotatory natural pheromone components, our synthetic C and D were levorotatory in hexane. In addition, none of them showed pheromone activity.48... 

Recently it has become known from work at Firmenich, that BINAP can be effectively replaced by the Josiphos and Daniphos ligands. [129] From diethyl-geranylamine one obtains after hydrolysis (S>citronellal, and from diethyl-nerylamine (R)-citronellal (analogous to (R)-BINAP). By attaching a linker to the unsubstituted cyclopentadiene ring, the catalyst can be immobilised on various carriers. In some cases this reduces the activity, but the stereoselectivity remains comparable. 

One of the shortest syntheses of an enantiomerically pure pheromone comes from Kenji Mori. [192] The key building blocks of the synthesis are (3H)-meth-yl-4-butanolide, available from Mitsubishi Rayon Co., and (S)-citronellal, which are coupled byway of a corresponding organolithium reaction. The overall yield comes to 16%. 

The group of Metz employed the proline-derived catalyst 159 in combinatiOTi with co-catalyst 160 to catalyze additions of (/ )- and (S )-citronellal (157) to 158 for the selective syntheses of the diastereomeric keto aldehydes 174 and 175. These intermediates could then be used to synthesize the marine sesquiterpenoids (—)-clavukerin A (176) (starting from (S )-157) and ( )-isoclavukerin A (177) (derived from (/ )-157) (Scheme 41) 162). 

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