Regio- and Stereocontrol in Rhenium-Catalyzed Transposition of Allylic Alcohols

Abstract

Direct catalytic transposition of allylic alcohols is a powerful approach to the synthesis of complex hydroxylated organic compounds.1 Several transition metal catalysts have been developed for this purpose, including vanadium,2 molybdenum,2 and rhenium reagents. 3 Among these, rhenium(VII) oxide and triphenylsilyl perrhenate have been found to be superior in terms of reactivity and chemoselectivity, displaying high activity at low temperatures with no competitive oxidation observed with some of the other catalysts. One drawback of the reversible process (eq 1) is a general lack of regioselectivity; 4 stereoselectivity in the transposition of primary allylic alcohols is also low.(1)In this communication, we describe a practical method that allows for control of the regioand stereoselectivity in the rhenium-catalyzed transposition of allylic alcohols, expanding the scope of the reaction for the stereoselective synthesis of complex molecules. 5 In our initial experiments, rearrangement of substrate 1 in the presence of Re 2 O 7 (2.5 mol %) occurred with low regio-and stereoselectivity as expected, delivering 2 with 60% conversion as a 3:2 mixture of diastereomers (Scheme 1). We hypothesized that the reaction medium must be slightly acidic due to formation of a catalytic amount of perrhenic acid (pK a = 1.25) 6 upon interaction of rhenium(VII) oxide with the substrate and/or adventitious water. 7 In the presence of a catalytic acid the rearranged product can in principle be trapped as an acetal or ketal, and then the 1,3-syn diastereomer should be favored on thermodynamic grounds. Remarkably, upon exposure of 1 to benzaldehyde dimethyl acetal and Re 2 O 7 (2.5 mol %), essentially a single product was formed in 94% yield after 20 h at room temperature. Thus, the rhenium catalyst performs a dual catalytic function as a transition metal catalyst for the hydroxyl group transposition and as an acid catalyst for acetal formation.Screening of the reaction parameters demonstrated that although a number of solvents can be used (toluene, Et 2 O, THF, CH 2 Cl 2 ), 8 dichloromethane provides the best results in terms © XXXX American Chemical Society *zakarian@chem.ucsb.edu . Supporting Information Available: Experimental procedures, copies of 1 H and 13 C NMR spectra. This material is available free of charge via the Internet at http://pubs.acs.org. of reaction rate. Typically, reactions are characterized by a rapid formation of a diastereomeric mixture of rearranged diol acetals (within ~20 min at room temperature) followed by slow equilibration of the acetals to the 1,3-syn product (3). NIH Public AccessThe influence of reaction time with alternative rhenium catalysts is summarized in Table 1. With all three catalysts studied, methyltrioxorhenium (MTO), Ph 3 SiOReO 3 , and Re 2 O 7 , the rearrangement/acetalization was complete within 3 h at room temperature. As expected, MTO is the least reactive catalyst. 2c,9 Notably, with all of the three rhenium catalysts the initial acetal formation was followed by equilibration to 3....

Expanding the Scope of Biomass‐Derived Chemicals through Tandem Reactions Based on Oxorhenium‐Catalyzed Deoxydehydration

“…[8] In 2012, we reported the methyltrioxorhenium (MTO)-catalyzed DODH reaction using a sacrificial alcohol (3-pentanol, 3-octanol, 1-butanol) as reductant/solvent. [13] However, we have found that oxorhenium complexes catalyze not only the DODH reaction, but also the [1,3]-OH shift of allylic alcohols [14] in a tandem manner, and we herein report novel modes of DODH (1,4-DODH and 1,6-DODH, respectively) from 2-ene-1,4-diols and 2,4-diene-1,6diols (Scheme 1). Oxorhenium-catalyzed DODH of diols using glycerol [10] or benzyl alcohol [11] as reductants were also independently reported by the Abu-Omar and Nicholas groups.…”

“…In our previous study on the MTO-catalyzed DODH of sugar alcohols, [9] we generally observed only complete DODH products. [14] To examine this hypothesis and gain insights into the origin of the observed exquisite selectivity in polyol DODH reactions, we tested a series of 2-ene-1,4-diol and 2,4-diene-1,6-diol substrates and indeed observed the unprecedented 1,4-DODH and 1,6-DODH reactions (Table 1). Likewise, d-chiro-inositol, muco-inositol, and allo-inositol all gave high benzene yields (> 45 %), without forming cyclohexa-2,5diene-1,4-diol and cyclohexa-3,5-diene-1,2-diol.…”

Catalytic Nucleophilic Allylation Driven by the Water–Gas Shift Reaction

“…The spectroscopic data matched those from the literature. 73 Data for 10p : 1 H NMR (500 MHz, CDCl 3 ) 5.79–5.70 (m, 2H, C(4)H, C(3)H), 4.16–4.10 (m, 2H, C(5)H 2 ), 3.42–3.37 (m, 1H, C(1)H), 2.34–2.29 (m, 1H, C(1)OH), 2.17–2.11 (m, 1H, C(cyclohexyl)H), 1.87–1.82 (m, 1H, C(cyclohexyl)H), 1.79–1.74 (m, 2H, C(2)H 2 ), 1.70–1.64 (m, 2H, C(cyclohexyl)H), 1.53 (s, 1H, br OH), 1.45–1.40 (m, 1H, C(cyclohexyl)H), 1.39–1.32 (m, 1H, C(cyclohexyl)H), 1.29–0.97 (m, 5H, C(cyclohexyl)H); 13 C{1H} NMR (125 MHz, CDCl 3 ) 132.3, 129.6, 75.4, 63.4, 43.4, 37.2, 29.2, 28.4, 26.7, 26.4, 26.3; MS (ESI) 207.1 (MNa + , 100); TLC R f 0.280 (Et 2 O/CH 2 Cl 2 , 4:1) [KMnO 4 ].…”

Re2O7-catalyzed reaction of hemiacetals and aldehydes with O-, S-, and C-nucleophiles

“…Perrhenates, best known as catalysts for large-scale alkene metathesis [2] and isomerization of allylic alcohols [3–10], have been shown to promote condensation of carbonyls with hydrogen peroxide or hydroperoxides [11–12], intramolecular displacements of reversibly formed hemiacetals and allylic alcohols [8,13], displacement of resonance-activated alcohols with electron-poor nitrogen nucleophiles [14], and a synthesis of homoallylated amines from condensation of carbonyl groups with an electron-poor amine in the presence of allyltrimethylsilane [15]. We now describe the Re 2 O 7 -promoted reactions of peroxyhemiacetals, hemiacetals, and alkoxyhydroperoxides with O -, S- and C -nucleophiles.…”