A Novel Aldol Condensation Alternative:α,β-Unsaturated Aldehydes from 3-Hydroxy-1-alkynes via Dihydrodioxepins

Abstract

The controlled aldol condensation between an aliphatic ketone and an acetaldehyde equivalent remains a challenge. One solution to this evergreen problem consists of the nucleophilic addition of acetylene to the ketone and the subsequent isomerization of the resulting 3-hydroxy-1-alkyne to the corresponding 2-alkenal. So far, however, the latter step could only be executed with acid-insensitive substrates. We now present a milder, three-step method which extends the scope of the procedure considerably. In the first step, the 3-hydroxy-1-alkynes are converted into 2-propynyl ethylene glycol monoethers; these then undergo base-catalyzed cyclization to give the dihydro-1,4-dioxepins, which are hydrolyzed in acidic medium in the third and final step.

Vinyl Ethers Containing an Epoxy Group: XXII. Synthesis and Base-Catalyzed Transformations of 1-(Allyloxy)- and 1-[2-(Vinyloxy)ethoxy]-3-(2-propynyloxy)propan-2-ols

“…Such cyclizations (which involve intramolecular nucleophilic addition of functional group at the acetylenic triple bond) are among the most widespread reactions leading to five-, six-, or seven-membered heterocycles containing one or two heteroatoms (N, O, S) [8,12, 13]. However, in the series of -(2-propynyloxy)alkan-1-ols, only 2-(2-propynyloxy)ethanol and its simplest derivatives R 1 C CC(R 2 )(R 3 )OCH(R 4 )CH(R 5 )OH (R 1 = R 2 = R 3 = R 4 = R 5 = H [3, 4, 7]; R 1 = R 2 = R 3 = R 4 = H, R 5 = Me, Ph; R 1 = R 2 = R 3 = R 5 = H, R 4 = Ph; R 1 = R 2 = R 3 = H, R 4 = R 5 = Me [3, 6]; R 1 = R 2 = R 4 = R 5 = H, R 3 = Me [7]; R 1 = R 4 = R 5 = H, R 2 = Me, R 3 = Ph [8]; R 1 = R 2 = R 4 = H, R 3 = R 5 = Me [3, 6, 7]; R 1 = Me, R 2 = R 3 = R 4 = R 5 = H [7]), 3-(2-propynyloxy)propan-1-ol [5], 2-(2-propynyloxy)cyclopentanol [7], and 2-(2-propynyloxy)cyclohexanol [3, 6, 7] were studied.Obviously, introduction of additional reaction centers, e.g., olefinic fragments with qualitatively different chemical natures of the double carbon-carbon bonds (specifically vinyloxy and allyloxy groups), into (2-propynyloxy)alkanol molecules should strongly extend the synthetic potential of both initial alkanols [1][2][3][4][5][6][7][8]12] and their cyclization products [1,8,14], as well as the range of their useful properties and the scope of practical application. Known representatives of this class of compounds are used in various fields (see, e.g., references in [1]), including the synthesis of dendrimers, dienes, -hydroxy and -oxo acids, -hydroxymethyl ketones, , '-dihydroxy ketones, polycyclic compounds (via functionalization or transformations of 1,4-dioxines) [15], and enediyne antibiotics (through key intermediates containing 2-vinyl-1,3-dioxolane fragments) [16].…”

“…Base-catalyzed intramolecular cyclizations of -(2-propynyloxy)- [2][3][4][5][6][7][8], -(2-propynylsulfanyl)- [9], and -(2-propynylamino)alkan-1-ols [10,11], as well as of their 2-haloallyl analogs [4,5,9], have been studied in sufficient detail. Such cyclizations (which involve intramolecular nucleophilic addition of functional group at the acetylenic triple bond) are among the most widespread reactions leading to five-, six-, or seven-membered heterocycles containing one or two heteroatoms (N, O, S) [8,12,13].…”

“…Such cyclizations (which involve intramolecular nucleophilic addition of functional group at the acetylenic triple bond) are among the most widespread reactions leading to five-, six-, or seven-membered heterocycles containing one or two heteroatoms (N, O, S) [8,12,13]. However, in the series of -(2-propynyloxy)alkan-1-ols, only 2-(2-propynyloxy)ethanol and its simplest derivatives R 1 C CC(R 2 )(R 3 )OCH(R 4 )CH(R 5 )OH (R 1 = R 2 = R 3 = R 4 = R 5 = H [3,4,7]; R 1 = R 2 = R 3 = R 4 = H, R 5 = Me, Ph; R 1 = R 2 = R 3 = R 5 = H, R 4 = Ph; R 1 = R 2 = R 3 = H, R 4 = R 5 = Me [3,6]; R 1 = R 2 = R 4 = R 5 = H, R 3 = Me [7]; R 1 = R 4 = R 5 = H, R 2 = Me, R 3 = Ph [8]; R 1 = R 2 = R 4 = H, R 3 = R 5 = Me [3,6,7]; R 1 = Me, R 2 = R 3 = R 4 = R 5 = H [7]), 3-(2-propynyloxy)propan-1-ol [5], 2-(2-propynyloxy)cyclopentanol [7], and 2-(2-propynyloxy)cyclohexanol [3,6,7] were studied.…”

“…Obviously, introduction of additional reaction centers, e.g., olefinic fragments with qualitatively different chemical natures of the double carbon-carbon bonds (specifically vinyloxy and allyloxy groups), into (2-propynyloxy)alkanol molecules should strongly extend the synthetic potential of both initial alkanols [1][2][3][4][5][6][7][8]12] and their cyclization products [1,8,14], as well as the range of their useful properties and the scope of practical application. Known representatives of this class of compounds are used in various fields (see, e.g., references in [1]), including the synthesis of dendrimers, dienes, -hydroxy and -oxo acids, -hydroxymethyl ketones, , '-dihydroxy ketones, polycyclic compounds (via functionalization or transformations of 1,4-dioxines) [15], and enediyne antibiotics (through key intermediates containing 2-vinyl-1,3-dioxolane fragments) [16].…”

“…The maximal yield of 3-(2-propynyloxy)propan-2-ol (IIa, isolated product) was 65-68% (yield of the crude product >80%) in the reaction of oxirane Ia with 2-propynol (1.18-1.25 equiv) at 75-85°C (reaction time 9.5-10 h; Table 1, run nos. 5,7,8). 3-(2-Propynyloxy)propan-2-ol (IIb) was synthesized in a similar way by heating a mixture of oxirane Ib and 2-propynol at a ratio of 1:1.67 in the presence of ~3 wt % of t-BuOK (80-85°C, 5 h; yield up to 95%); this reaction was considered in detail in the preceding communication [1].…”