A-Damascone

KH/HMPT is also useful for selective 3-cleavage of tris(homoallylic) alcohols, as shown by a new synthesis of a-damascone (4). In general, l,l-dimethyl-2-pro-penyl and benzyl groups are cleaved more readily than a l-methyl-2-propenyl group,... 

Syntheses have been reported for several other natural products related structurally to carotenoids, viz. dihydroactinidiolide (123) and tetrahydroactinidiolide (124), trans- and cis-a-damascone (125), dihydroedulans I and II, (51) and (52), bicyclodamascenones A and B, (53) and (54), the diastereoisomeric caparrapi oxides (126), ( )-a-chamigrene (127), and the novel passion-fruit ionone derivatives (47) and (48). ... 

The acid-catalyzed cyclization of the chiral enamine (134) produces (R)-a-cyclocitral (135) and hence (R)-trans-a-damascone (136) in 33 % enantiomeric excess 152). 

Although a small amount of acyclic terpene acids such as geranic acid and citronel-lic acid occurs in many essential oils, often as esters, they are rarely used in perfume and flavor compositions. Methyl geranate is an intermediate in a-damascone synthesis and is sometimes needed in the reconstitution of essential oils. 

Werkhoff P, Bretschneider W, Giintert M, Hopp R, Surburg H (1991) Chirospecific analysis in flavor and essential oil chemistry. Part B. Direct enantiomer resolution of trans-a-ionone and trans-a-damascone by inclusion gas chromatography. Z Lebensm Unters Forsch 192 111 Larsen M, Poll L (1990) Odour thresholds of some important aroma compounds in raspberries. Z Lebensm Unters Forsch 191 129... 

Zenoni G, Qrattrini F, Mazzotti M, Fuganti C, Morbidelli M (2002) Scale-up of analytical chromatography to the shmdated moving bed separation of the enantiomers of the flavor nor-terpenoids a-ionone and a-damascone. Flavour Fragr J 17 195... 

The thiolester was readily converted to target molecules, (S)-a-cyclocitral and (5)-a-damascone. 

Hydrogenation of 2,4,4-trimethyl-2-cyclohexenone with rrans-RuCl2(tolbinap)(dpen) and (CH3)3COK under 8 atm of hydrogen gives 2,4,4-trimethyl-2-cyclohexenol quantitatively with 96% ee (Scheme 1.70) [256,275,276]. In this case, unlike in the reaction of aromatic ketones, the combination of the R diphosphine and S,S diamine most effectively discriminates the enantiofaces. The chiral allylic alcohol is a versatile intermediate in the synthesis of carotenoid-derived odorants and other bioactive terpens such as a-damascone and dihydroactinidiolide [277]. 

Enantioselective protonation. (R)- and (S)-a-Damascone (4) have been prepared by a Grignard reaction followed by enantioselective protonation with l1 and 2,3 both available from (-)- or (+ )-ephedrine. Thus protonation of the ketone enolate 3 with (+ )-l or (- )-2 furnishes (S)- or (R)-a-damascone (4), respectively. 

R)-a-cyclocitral (155) was obtained in up to 33% optical yield. The latter was used to synthesize ( + )-(R)-trans-a-damascone (156).64 A rapid, economical preparation of safranal (157) involves acid-catalysed cyclization of the anilide of citral, followed by N-bromosuccinimide treatment of the cyclocitrals thus produced.65... 

Fehr C (2006) Synthetic applications of enantioselective protonation and case study for (S)-a-damascone. In 45th Tutzing Symposiom Organocatalysis, Tutzing, Germany, 8-11 October 2006 Fujita K, Taguchi Y, Oishi A (2003) JP 3459986... 

The rose ketones 11, first discovered ini970 [gl] in Bulgarian rose oil, and named damas-cones, show unique organoleptic properties. Because of this they have elicited great interest, also as target molecules for new synthetic methods. a-Damascone 12 possesses a quite unique fruity odor, and its utilization aliows the creation of perfumistic notes otherwise difficult to achieve. 

Treatment of (+)-epoxy-a-dihydroionone with hydrazine hydrate gives as one of the reaction products alcohol 13, which was transformed by oxidation with MnO to (+)-[R >-a-damascone 12 in 65% e. e., t hus estabiishing its absolute con-figuration [22. ... 

A new access to a-damascone by selective kinetic protonation of a-ketone enoiate, formed by reaction of an ester enoiate with nucieophiles, has recently been described by Fehr and Galindo [22] (scheme 2). 

The same authors found that the prochiral enoiate 16 can, under certain conditions, be protonated enantioselectively, using ephedrine derivatives as proton sources [23]. These compounds are availabie in their opticaliy pure forms, thus both enantiomers of a-damascone can be prepared in about 70% optical yield starting with the same ketone enoiate and using the appropriate optical form of the proton source. Enantiomerically pure a-damascones 12, 2 have been obtained by repeated recrystallization. 

The damascones are a group of materials related to the ionones, but in which the enone unit is transposed. They are components of rose oils and have very intense fruity-floral odours. The damascenones, which contain a second double bond in the ring, are also very much sought after. One synthesis of a-damascone from methyl a-cyclogeranate is shown in Scheme 4.40. A double Grignard addition gives the tertiary alcohol. Heating of this in the presence of base, to prevent elimination... 

The choice of the chiral proton source, cation(s), (chiral) base, auxiliaries and temperature dramatically changes the enantiomeric excess of (/ )- or (S)-a-damascone (11) on protonation of the enolate and isomerization of the intermediate ketone156. 

So, for example, the natural product a-damascone (9) cydises to (10) in add solution. The disconnection is of the bond (a in 11) opposite the carbonyl group in the five-membered ring and the synthesis is carried out by treating the dienone (12) with add or Lewis add. ... 

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