Vanadium(V)-Catalyzed Oxidation of (3R)-Linalool - The Selective Formation of Furanoid Linalool Oxides and their Conversion into Isocyclocapitelline Derivatives

Abstract

Oxidation of (3R)-linalool (2) with tert-butyl hydroperoxide (TBHP) occurs at the 6,7-position to selectively afford linalool oxide cis-1, if catalyzed by vanadium(V) Schiff base complexes 4. Substituted tetrahydrofuran cis-1 and its isomer trans-1 served as starting materials for short concise syntheses of β-carbolines cis-3 and trans-3 which are lower homologues of alkaloids (-)-isocyclocapitelline and (+)-cyclocapitelline.(-)-Isocyclocapitelline (Scheme 1), (+)-cyclocapitelline, and (+)-chrysotricine are tetrahydrofuran-derived β-carboline alkaloids, which have been extracted from far eastern medicinal plants. 1,2 From a biosynthetic point of view it seems likely that linalool oxides 1 and therefore linalool 2 serve as precursors for the formation of these alkaloids. 1,3 In organic synthesis, however, the abovementioned β-carbolines are generally obtained in multistep transformations that use other precursors than terpenol 2 as starting material for the following reasons. 4 Conversion of substrate 2 into functionalized tetrahydrofurans 1 requires selective oxygenation at the 6,7-π-bond which is attainable by e.g. peracids 5 or the combination of H 3 CReO 3 /H 2 O 2 . 6 Unfortunately, the observed diastereoselectivities in these reactions are negligible. If oxidized with tert-butyl hydroperoxide in the presence of an early transition metal catalyst such as VO(acac) 2 , 7 a selective conversion of linalool 1 into the corresponding 1,2-epoxyalcohol has been reported. 8,9 In view of the significance of linalool oxides 1 as versatile building blocks, 10 and the contemporary interest in tetrahydrofuran-derived β-carboline alkaloids, 1,2,4 we have developed a new stereoselective access to furanoid linalool oxide cis-1 and disclose our latest results in this communication as a part of the synthesis of hitherto unknown β-carbolines cis-3 and trans-3.The selected strategy for diastereoselectively oxidizing substrate 2 at the 6,7-position is based on the use of TBHP as primary oxidant and vanadium(V) Schiff base complexes 4 as catalysts. 11 The latter reagents were chosen for this purpose, since vanadium compound 4a does not catalyze the epoxidation of allylic alcohols 12 but efficiently mediates diastereoselective formation of functionalized tetrahydrofurans from bishomoallylic alcohols and TBHP. 11,13,14 In an initial experiment, terpenol 2 was treated with TBHP and 10 mol% of vanadium(V) catalyst 4a in CHCl 3 at 20°C for 12 hours. Previous optimization studies had shown that these conditions provide high selectivities for tetrahydrofuran formation in combination with a satisfactory peroxide efficiency. 14 Purification of the reaction mixture furnished furanoid linalool oxides 1 (62%, cis:trans = 61:39), 1,2-epoxylinalool oxides 5 (6%, cis:trans = 56:44), and pyranoid linalool oxides 6 (3%, cis:trans = 40:60) (Scheme 2). [15][16][17] No 1,2-epoxides of linalool were detected ( 1 H NMR, GC). 8,9 The relative configurations of major isomers of heterocycles 1, 5, and 6 were established by NMR experiments (NOE, HMBC, HM...

(Schiff‐base)vanadium(V) Complex‐Catalyzed Oxidations of Substituted Bis(homoallylic) Alcohols − Stereoselective Synthesis of Functionalized Tetrahydrofurans

“…for the formation of tetrahydrofuran-derived β-carboline alkaloids. [71] Experimental Section 3 were obtained from Fluka or Aldrich and were used as received. Petroleum ether was distilled prior to use (b.p.…”

Application of the Asymmetric Pictet–Spengler Reaction in the Total Synthesis of Natural Products and Relevant Biologically Active Compounds

“…Linderaggrine A 85 is a β-carboline alkaloid, from the roots of L. aggregata . β-Carboline alkaloids are a predominant class of biologically active naturally occurring compounds having an extensive range of pharmacological and structural diversity [ 171 , 172 , 173 ]. The successful construction of linderaggrine A 85 and 89 gave unambiguous evidence for the determination of the naturally extracted product.…”

A Practical Laboratory-Scale Synthesis of All Eight Stereoisomeric Forms of Terpene Linalool Oxide

“…All these monoterpenes are important flavours and are thought to give a relevant contribute to the scent of different foods and beverages of vegetal origin such as grape [5], papaya [2,6], wine [7], and tea [8] where they are often present as glycosides derivatives [9,10] or less frequently as acetate [11]. In addition, these monoterpene isomers are important chiral building blocks for the synthesis of different bioactive natural products [12][13][14][15][16][17]. As we are involved in a number of studies focused on the stereoselective synthesis of flavors, fragrances and sesquiterpenes structurally related to the linalool and linalool oxides [18][19][20][21], we became interested in developing a synthetic method for the preparation of all the linalool oxide stereoisomers.…”

“…Accordingly, distillation of the crude reaction mixture allowed the separation of pyranoid As we are involved in a number of studies focused on the stereoselective synthesis of flavors, fragrances and sesquiterpenes structurally related to the linalool and linalool oxides [18][19][20][21], we became interested in developing a synthetic method for the preparation of all the linalool oxide stereoisomers. Although a number of chemical [12,14,[22][23][24][25][26][27][28][29][30] and chemoenzymatic syntheses [31][32][33][34][35] of enantioenriched linalool oxides have been previously reported, only a few [22][23][24] are suitable for the stereoselective preparation of all the isomeric forms of these monoterpenes. Among the latter three approaches, Klein et Al.…”