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

Abstract

~ ~~The transformation of 36 bis(homoallylic) alcohols VIl to alkenones IX and X via /I-cleavage of their potassium alkoxides VIIa in HMPA has been investigated (cf. Scheme 2). These studies have established an order of /]-cleavage for 2-propenyl, l-methyl-2-propeny1, 2-methyl-2-propeny1, 1, I-dimethyl-2-propeny1, and benzyl groups in alkoxides 49a-56a and have allowed a comparison between the /I-cleavage reaction and the oxy-Cope rearrangement in alkoxides 74a 83a. As illustrative synthetic applications, a two-step preparation of propenyl ketoncs 1 5 4 2 from carboxylic esters is dcscribcd, together with syntheses of' or-turmerone (48), cc-damascone ((E)-71), a-damascone ((E)-109) and /I-damasccnone ((I?)-1 11).

β‐Cleavage of Bis(homoallylic) Potassium Alkoxides. Preparation of 3‐Hydroxypropyl and 4‐Hydroxybutyl Propenyl Ketones from γ‐ and δ‐Lactones. Synthesis of (±)‐Rose oxide

“…For 10,11,13, and 14, the hydroxy-ketone tautomer is energetically favoured, whereas the introduction of a Me group in 16 and 17 results in a reversal of this situation, and it is the lactol tautomer which is relatively more stable. As previously observed in analogous systems [5], the formation ofP,y-unsaturated ketones VI is preferred with respect to their a$ -unsaturated isomers VII. This result is kinetically controlled and reflects a site-selective a-protonation of the intermediate potassium dienolate V formed from the P-cleavage of the bis(homoally1ic) alkoxide IVa (cf.…”

Scalable Preparation of Enantioenriched (S)-5-methylhept-2-en-4-one. Synthesis and Aroma Properties of Achiral Analogues Thereof

“…Inspired by the aldol-based approach [6] to racemic 5-methylhept-2-en-4-one [7][8][9][10][11][12][13][14][15][16], we have designed our synthetic strategy towards enantioenriched 1 with key focus on the suppression of the associated epimerisation and use of naturally occurring substrates throughout the multigram sequence (Scheme 1). Thus, the initial activation [17] of natural (S)-2-methylbutanoic acid 2 (88% ee) followed by one-pot condensation of intermediary acyl imidazole with potassium ethyl malonate furnished the β-ketoester 3 in 90% yield in 2 steps.…”

“…General experiment for the preparation of (di)allyl alcohols(13)(14)(15)(16) To a freshly prepared solution of 1,2-dimethylpropenyl lithium 12 in anhydrous THF was added the respective aldehyde or ester dropwise at low temperature over 5 min. under argon.…”

Methallylmagnesium Chloride

“…7 Addition of excess methallylmagnesium chloride to an ester leads to the tertiary alcohol (eq 1). Exposure of the alcohol to Potassium Hydride in HMPA at 40 • C results in cleavage of one allylic C-C bond with loss of methallyl anion, and irreversible proton transfer to form the ketone enolate.…”