Synthesis of (E)‐1‐Propenyl Ketones from Carboxylic Esters and Carboxamides by Use of Mixed Organolithium‐Magnesium Reagents. Synthesis of α‐Damascone, β‐Damascone, and β‐Damascenone

Abstract

The novel reagents formed by combination of allylmagnesium chloride and a strong non-nucleophilic lithium base (LiNR,) convert non-or slowly enolizable carboxylic esters or carboxamides into 2-propenyl ketones which are protected from further reaction by their in situ conversion into enolates. This modified Grignard reaction is applied to efficient syntheses of a -damascone, 8-damascone, B-damascenone, and various other (E)-1-propenyl ketones.

2,6,6-Trimethylcyclohex-2-enecarboxylic acid

“…For information on the title compound as used as a key intermediate in chemical synthesis, see: Eugster et al (1969); Naef & Decorzant (1986); Snowden et al (1982); Fehr & Galindo (1986; Heather et al (1976). For hydrogenbond graph-set notation, see: Etter et al (1990); Bernstein et al (1995).…”

“…The title compound is a key intermediate for the synthesis of aroma compounds such as alpha, beta methyl cyclo geranate (Eugster et al, 1969), alpha damascone (Naef & Decorzant, 1986;Snowden et al, 1982), beta damascone (Fehr & Galindo, 1986), gamma damascone (Fehr & Galindo, 1995) and strigol which is a highly potent stimulant for the germination of seeds of parasitic weeds striga and orobanche (Heather et al, 1976). Moreover, the 2,6,6-tri methylcyclohexenyl moiety is a basic moiety for natural product of carotenoid, which is a naturally occurring organic pigment in the chloroplasts and chromoplasts of plants.…”

Flavours and Fragrances

“…The acid-catalysed isomerisation of the double bond leads to racemic α-damascone in satisfactory yields. [40] At elevated temperature, a second competing mechanism is the decomposition of the ester enolate to a ketene, followed by a Grignard reaction. [41] …”

β‐Cleavage of Bis(homoallylic) Potassium Alkoxides. Two‐Step Preparation of Propenyl Ketones from Carboxylic Esters. Synthesis of ar‐Turmerone, α‐Damascone, β‐Damascone, and β‐Damascenone

“…) in HMPA at 20" was followed by heating of the resulting potassium alkoxides 49a-56a until reaction was complete. After the standard aqueous workup (vide supra), the *) Small amounts ( < 3%) of (2)-X (R2 = H) dctected in the product mixtures of Entries 1,3,5,7,Y I I" x IV"…”

“…) in HMPA at 20" was followed by heating of the resulting potassium alkoxides 49a-56a until reaction was complete. After the standard aqueous workup (vide supra), the *) Small amounts ( < 3%) of (2)-X (R2 = H) dctected in the product mixtures of Entries 1,3,5,7,Y,/ I,and I3 (cf: Table Z) by 'H-NMR and GC/MS analysis may be formed either directly by y-protonation of VIII or, indirectly, from the dienol of IX uia a themolytic 1,s-H shift; as evidence for the latter hypothesis, distillation (lOS-llW/lS Torr) of a crude 1.S:l mixture 39/(E)-40 resulted in the formation of a 5:2.5:1 mixture 39/(2)-40/(E)-40. dienones 57-67 derived from P-cleavages were isolated in 76-84% yield (cf Table 2). In each experiment, the product mixture was analysed by TLC, GC/MS coupling, and 'H-NMR (360 MHz) spectroscopy, and in three cases (cf.…”