Convenient preparation of carbonyl compounds from 1,2-diols utilizing Mitsunobu conditions

Abstract

Abstract1,1-Disubstituted 1,2-diols are efficiently converted into carbonyl compounds by reaction with triphenylphosphine and diethyl azodicarboxylate. © 2000 Elsevier Science Ltd. All rights reserved.Keywords: Mitsunobu reactions; diols; aldehydes.The Mitsunobu reaction is a useful synthetic tool which allows the conversion of an alcohol function into a wide variety of functional groups. [1][2][3][4][5][6][7][8] ROOC-N_N-COOR + Ph 3 P + R OH + Nu : → Nu-R + Ph 3 PO + ROOC-NH-NH-COOR Cyclic compounds are formed when the alcohol molecule contains a suitably placed nucleophile. Epoxides are obtained from acyclic 1,2-diols under the Mitsunobu conditions 9 and from cyclic trans-1,2-diols. [10][11][12][13] Under the same conditions triphenylphosphoranes resulted from cyclic cis-1,2-diols. [11][12][13][14] Methyl shikimate (8a), having cis-and trans-diol groups, leads to the corresponding epoxide 8b, under these conditions. 15 During our research on the synthesis of bioactive compounds from labdane diterpenes we have found that diol 12a is transformed with excellent yield into drimenal (12b) 16 when it is treated with triphenylphosphine (TPP) and diethyl azodicarboxylate (DEAD) in benzene. In order to elucidate the scope and synthetic application of this reaction the behaviour of a variety of 1,2-diols with these reagents has been studied. The results obtained are summarized in Table 1 and compared with those previously reported. As may be seen, monosubstituted and disubstituted 1,2-diols are converted into epoxides or phosphoranes, depending on whether the hydroxyl groups adopt an antiperiplanar (cyclic trans-diols and acyclic diols) or an eclipsed conformation (cis-diols), respectively. The formation of phosphorane 3b from diol 3a can be attributed to the bulky dioxolane groups which prevent the hydroxyl groups from adopting the anti disposition. 1,1-Disubstituted-1,2-diols lead to the formation of aldehydes or ketones, depending on whether the less substituted carbon is primary or secondary. Even acyclic 1,1-disubstituted * Corresponding author.

Recent Advances in the Mitsunobu Reaction: Modified Reagents and the Quest for Chromatography‐Free Separation

“…The products available via the Mitsunobu reaction have been expanded or the procedure has been improved to include styrene oxides with a high level of stereoretention, [32] oxetanes, [29] lactones from hindered chiral alcohols with retention of configuration, [73] aldehydes from 1,1-disubstituted-1,2-diols, [85] carbamate esters, [57,86,87] γ-lactams from amino alcohols, [88] primary amines, [89] tertiary benzylamines, [40] alkylated hydrazines, [90] nitriles, [41,61] isocyanates, [31] thiocyanates, [91] hydroxyalkyl azides, [69,92] and cisor trans-1,2-diazides from epoxides or trans-diols. [93] Hydra- zine derivatives can be obtained directly from the azodicarboxylate and an alcohol, [94] vinylhydrazinecarboxylates from ketones in the presence of dimethyl azodicarboxylate, [95] and hydrazylmethyl uracil derivatives from N 3 -benzyluracil, TMAD, and N-hydroxymethylphthalimide.…”

A Direct Method for the Efficient Synthesis of Benzylidene Acetal at Room Temperature

“…To our delight, it indeed afforded the corresponding benzylidene acetal (3a) in 69 % yield, along with small amount of 2-phenylpropanal (4) [19] (entry 1, Table 1). ), phenylpropane-1,2-diol (1.1 eq.)…”

Mechanistische Charakterisierung von zwei Sesquiterpen‐Cyclasen aus dem phytopathogenen Pilz Fusarium fujikuroi

“…[12] Unter Verwendung eines Mitsunobu-Protokolls [13] ergab die selektive Eliminierung des tertiä-ren Alkohols das exocyclische Alken 4 in 74 % Ausbeute (bemerkenswerterweise wurde ein Naturstoff mit identischen spektroskopischen Daten, aber unterschiedlicher Struktur publiziert). [14] Der sekundäre Alkohol wurde durch SteglichVeresterung in das Formiat 5 überführt.…”

“…Die vorgeschlagenen Mechanismen wurden experimentell durch enzymatische Konversion markierter FPP-Isotopomere getestet. [18] (1,1-2 H 2 ,11-13 C)FPP resultierte in markiertem 1, das ein Singulett bei d = 37.8 ppm für C11 im 13 C-NMR-Spektrum aufwies, wodurch angezeigt wurde, dass kein Deuterium an diesem Kohlenstoffatom angebunden war (Abbildung 2 A). Daraus kann geschlossen werden, dass die Umwandlung von A zu 6 nicht über eine 1,3-Hydridverschiebung über B abläuft.…”

“…Daraus kann gefolgert werden, dass Weg a der einzig relevante für die Reaktion von 6 zu D ist. Ein Inkubationsexperiment mit (13-13 C)FPP resultierte in verstärkten 13 C-Signalen sowohl für C12 als auch C13 (Abbildung 2 C), woraus ableitbar ist, dass die Isopropylgruppe in Kation A nicht konformativ fixiert ist, sondern vor der folgenden 1,2-Hydridverschiebung zu C frei rotieren kann.…”