Regio- and Stereoselectivity of Diethylaluminum Azide Opening of Trisubstituted Epoxides and Conversion of the 3° Azidohydrin Adducts to Isoprenoid Aziridines

Abstract

The regioisomer ratios (3 degrees,2 degrees /2 degrees,3 degrees ), and in some cases the stereochemistry, of vicinal azidohydrins formed in reactions of 11 trisubstituted terpene epoxides with Et(2)AlN(3) in toluene are reported. The more highly substituted azide usually predominated (3 degrees,2 degrees /2 degrees,3 degrees ratios >or= 40:1 to 2.5-1) in accord with a Markovnikov orientation and an S(N)1-like transition state. Reversed regioisomer ratios were observed with 6,7-epoxygeranyl acetate (1:2.5) and cis-1,2-epoxylimonene (1:3.3 to 1:10). The tertiary azido diols from 2,3-epoxygeraniol, 2,3-epoxyfarnesol, and 2,3-epoxynerol were formed as single isomers with inversion of configuration at C3 (>or= 35-40:1 for the C(10) azido diols). The regioselectivity was affected by the presence and proximity of oxy functional groups on the epoxide substrate (OH, OAc, and OSi-tBuMe(2)), the equivalents of Et(2)AlN(3), and additives (EtOAc or EtOH). The results and trends are rationalized by consideration of the structural and stereoelectronic characteristics of proposed diethylaluminum epoxonium ion intermediates and transition states, together with the nucleophilicity of the azide donor. Six of the 3 degrees,2 degrees azidohydrins were converted to the corresponding aziridines by primary-selective silylations of four azido diols, mesylations, and reductive cyclizations with LiAlH(4).

Construction of the 1,2-Dialkenylcyclohexane Framework via Ireland-Claisen Rearrangement and Intramolecular Barbier Reaction: Application to the Synthesis of (±)-Geijerone and a Diastereoisomeric Mixture with Its 5-Epimer

“…Protection of the hydroxyl group in geraniol (2) by acetyl chloride in pyridine gave 3 in 84% yield. Selective epoxidation of 3 at the double bond between C-6, C-7 with m-chloroperoxybenzoic acid afforded 4 (72%), and the ring cleavage reaction was undertaken with periodic acid to afford aldehyde 5 (80%) [27,28]. Next, protection of the aldehyde group of 5 gave acetal 6 in 90% yield, and removal of the acetyl group of 6 with anhydrous potassium carbonate afforded alcohol 7 in 82% yield.…”

SO3H-Carbon derived from glycerol: An efficient and recyclable catalyst for smooth and regioselective azidolysis of oxiranes in water

“…Excellent yields of the desired β-azido alcohols are obtained with a reversal of regioselectivity indicating attack at the less substituted carbon of the aliphatic oxiranes (Entries 2-7, Table 2), while styrene oxide (Entry 1, Table 2), as an aryl oxirane formed the major product as 2-azido-2-phenylethanol, by the attack of azide nucleophile at the benzylic position, this is due to the formation of a stable benzyl carbocation during mechanism, is evidenced by electronic factors [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40], whereas in the case of aliphatic oxiranes (Entries 2-7, Table 2), steric factors predominate over electronic factors, thereby facilitating attack at the less hindered carbon atom of the oxirane ring. Furthermore, oxiranes derived from cycloalkenes, such as 7-oxabicyclo [4.1.0]heptanes (Entry 2, Table 2), reacted smoothly in SN2 fashion to afford the corresponding azidohydrine; and the reaction was completely anti-sterioselective, thus resulting in trans isomer only.…”

“…However, the azide opening is promoted by traditional homogeneous systems as metal chlorides [25,26], salts [27] and alkyl metal azides [28][29][30][31][32]. Some heterogeneous catalysts, relying on the use of traditional solid acids such as amberlite IRA-400 supported azide [33].…”

Intensification of organic reactions with hybrid flow reactors

“…In fact, the same experiment carried out in exactly the same conditions but using bare silica instead of acid-functionalized silica gave very poor yields. The three different limonene 1,2-epoxide opening products (entries 7-9) [19][20][21], which exclusively gave the trans-diaxial hydroxyether [22], were subjected to a series of NMR studies. [23] 92/84 100/68 2 styrene epoxide EtOH [23] 88/82 99/64 3 styrene epoxide iPrOH [23] 86/81 98/68 4 cyclohexene oxide MeOH [23] 100/100 100/89 5 cyclohexene oxide EtOH [23] 100/100 100/83 Figure 2).…”