The Synthesis of β,γ‐ and α,β‐Unsaturated Aldehydes via Polyene Epoxides

Abstract

SummaryA substitute for the Darzens glycidic ester synthesis for converting unsaturated ketones or aldehydes into the homologated b, y -or a,B-unsaturated aldehydes employing sulfur ylides is described. The carbonyl group is converted into the unsaturated oxirane which is then rearranged to the new aldehyde. High yields of isomerically pure aldehydes are available by this method and the process is of practical importance in the conversion of p-ionone into the p-CI4-aldehyde, a key intermediate in the Isler synthesis of vitamin A. The efficient preparation of aand /I-cyclocitral by the novel process is also described.The development of a commercial synthesis of vitamin A by Isler et al. is one of the major industrial achievements of the fifties [l]. This complex process [ 2 ] is still the major source of this essential vitamin, and the overall synthetic scheme has changed very little in the past twenty-five years.One key step of this process is the formal addition of one C-atom to p-ionone (1) (Scheme I ) , using the Darzens glycidic ester [3] reaction and proceeding through the aldehyde 2 originally used by Milas et al.[4] in their vitamin-A work; the glycidic ester is hydrolyzed, decarboxylation then leads to the aldehyde enolate and kinetic protonation results in the aldehyde 2; further exposure to base then yields the thermodynamic product 3. While the overall yield for this transformation is good (84-86%), the economy of the process in today's market place leaves much to be desired. An excess of methyl chloroacetate and sodium methoxide has to be used to add the C-atom and it would be better to just add this C-atom without waste.A similar process involving epoxide 4, can also be envisioned as a possible route to 2. Therefore, the epoxide 4 was prepared (94% yield) from p-ionone (1) by the action of (dimethylsu1fonio)methanide [ 5 ] . The conversion of this epoxide to the aldehyde 2 initially proved difficult but eventually yielded to the action of magnesium bromide [6].

4-Hydroxy-7,8-dihydro-.beta.-ionol: natural precursor of theaspiranes in quince fruit (Cydonia oblonga, Mill.)

“…NMR (60 MHz, CDC13), in close agreement with published data (Rosenberger et al, 1980); FTIR (vapor phase, v, cm'1) 3006,2965,2929,1732,1452,1359,1205,1156, 871; EIMS m/z (%) isomer 1 (Rt 1437) 43 ( 100) 55( 28 ) 69 (48) 79 (23) 93 (52) 107 (51) 121 (52) 134 (5) 149 (28) 159 (3) 174 (2) 177 (2) 192 (13, M+); EIMS m/z (%) 0021-8561/88/1436-0560$01.50/0 4-Hydroxy-7,8-dihydro-/3-ionol Table I. Spectral Data of 4-Hydroxy-7,8-dihydro-/S-ionol (2)…”

Efficient Access to All‐Carbon Quaternary and Tertiary α‐Functionalized Homoallyl‐type Aldehydes from Ketones

“…Thes ubstrate scope was broad, and interestingly,a ni mportant intermediate (57)f or the synthesis of vitamin D [28] was obtained in as ingle highyielding synthetic operation. Significantly,d uring work-up and purification, the b,g-unsaturated aldehydes spontaneously isomerized to the more stable a,bunsaturated ones (4, 56-62).…”

Asymmetric Ylide Reactions: Epoxidation, Cyclopropanation, Aziridination, Olefination, and Rearrangement

“…Even using the well-established Jacobsen asymmetric epoxidation, the preparation of styrene oxide in high ee is still a challenge. Moreover, the asymmetric methylene transfer from chiral sulfonium ylides to CO bonds has not been successful to date (Scheme ). ,,35a, Unfortunately, Hiyama's work was questioned and considered incorrect five years later 22 …”