Model studies probing the amino-Claisen rearrangement approach to hydroisoquinoline synthesis. Development of methods for stereocontrolled introduction of reserpine E ring type functionality (original) (raw)
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Base mediated regioselective synthesis of highly functionalized conjugated enones
Tetrahedron Letters, 2015
Functionalized α,β-unsaturated ketones are biologically and pharmaceutically important skeletons and act as useful building blocks in synthetic organic chemistry. 1 This skeleton is present as substructure in a variety of natural products. 2 The synthetic potential of enones can be evaluated by their use as precursors in several carboncarbon bond-forming reactions; for example Michael addition, 3 cyclopropanation, 1,3-dipolar cyclo-addition and Diels-Alder reactions. In general, these compounds are prepared by various conventional condensation reactions as aldol-or Knoevenagel-type reactions. Wittig, Horner-Wadsworth-Emmons and Julia and Peterson olefination approaches are also used for the synthesis of enones. 5 Enones can also be synthesized by Meyer-Schuster rearrangement, which involves isomerization of propargylic alcohols through 1,3-shift of the hydroxyl moiety. 6 Recently, enone has been synthesized by Renium, 7 gold (III) 15 and oxovanadate complex 8 mediated Meyer-Schuster rearrangement. α,β-Unsaturated ketones were also synthesized by dibutyltin dimethoxide catalyzed condensation of aldehydes and alkenyl trichloroacetate. 9 Li et al have reported the synthesis of enone by reaction of aldehydes and methyl vinyl ketone in presence of Ti(IV) catalyst. 10 Base mediated oxidative decyanation approach for the synthesis of ketones from secondary nitrile was first reported by Kharasch and Sosnovsky. 11 They proposed that secondary nitrile absorbs molecular oxygen in presence of strong base to afford ketone through oxidative decyanation. In 1973, Watt's group started to work on general oxidative decyanation procedure for the synthesis of ketones from secondary nitriles. He has developed various approaches 12-15 for the direct oxygenation of anion of secondary nitrile. Kulp et al have also reported 16,17 the oxidative decyanation of various diaryl, arylalkyl and dialkyl acetonitriles. Recently, formation of diarylketone from diarylacetonitrile was carried out under solid liquid phase transfer catalytic conditions. 18
A New Asymmetric Synthesis of trans -Hydroisoquinolones
Organic Letters, 2001
A convenient enantioselective synthesis of trans-hydroisoquinolones is described. This synthesis capitalizes on the ready availability of enantioenriched 2-substituted cyclohexenols by exploiting the asymmetry of an allylic carbon−oxygen σ bond to control carbon−carbon bond formation in pinacol-terminated cyclizations of N-acyliminium cations. Decahydroisoquinoline rings are found in structurally diverse isoquinoline alkaloids as well as several important clinical agents. 1,2 Morphine (1) and reserpine (2) are well-known members of these groups. Because of the wide occurrence and pharmacological importance of trans-hydroisoquinolines, the development of new asymmetric routes to this ring system remains an important objective in organic synthesis. In recent years, we have invented a suite of carbon-carbon bond-forming ring constructions that couple pinacol rearrangements with cationic cyclization reactions. 3,4 The accompanying communication in this issue details reactions wherein pinacol rearrangement of a ring carbon terminates a cationic cyclization process. 5 Much less developed are cyclization-pinacol reactions concluded by hydride migration. 6 A new sequence of this latter type, which we envisaged
Tetrahedron, 2009
An efficient and simple procedure for the syntheses of 4-aryl-1,2,3,4-tetrahydroisoquinolines and 1-aryl-2,3,4,5-tetrahydro-3-benzoazepines has been developed. The approach uses easily available starting materials and requires just three steps. The hydroamination of an enol carbamate is the key step. This general and direct method has been applied to the total synthesis of the natural alkaloid cherylline and to biologically active 3-benzoazepines as well.
Tetrahedron Letters, 1977
The Claisen rearrangement of ally1 vinyl ethers leading to y,b-unsaturated carbonyl compounds has proven exceptionally useful as a general method in natural product synthesis.3 Similarly, the Cope and Oxy-Cope transformations have been employed frequently to construct complex ring systems of target molecules.4 Surprisingly, however, incorporation of the related aza-Claisen rearrangement,' which converts N-allyl-vinylamines or ammonium salts to their corresponding unsaturated imines or iminium salts, into preparative sequences has been much less
An efficient chemo-enzymatic approach to (+)-meroquinene
Tetrahedron: Asymmetry, 1990
Meroquinene (+)-1 was prepared in an efficient and stereocontrolled fashion from (lR-2S)+cyclohexene dimethanol monoacetate (-)-8. Key steps are the enzyme-catalyzed hydrolysis of the available diacetate 5 to (-)-8 and of the intermediate diester 17 to h&ester 18, which allow the stereo and regiocontmlled elaboration of the vicinal vinyl and carboxymethyl groups. Meroquinene (+)-1 [(3R,4S)-3-vinyI-4-piperidine acetic acid], firstly obtained by degradation of cinchonine 2,'~~ has attracted wide interest in the last years because it represents a key-intermediate in the synthesis of some medicinally valuable Cinchona alkaloids such as quinine 3 and cinchonamine 4.' This remarkable importance, coupled with its relatively straightforward structure, makes memquinene (+)-1 a challenging target for synthetic works. Many reports concerned with the racemic synthesis of 1 have appeared in the literature." In one cas$ a resolution step of a racemic intermediate allowed to obtain both (+)-I and non natural (-)-1. An enantioconservative approach to (+)-I was designed by Brown6 starting from secologanine which embodies the entire carbon skeleton of (+)-1 with the correct chirality at the stenogenic centers. Very recently Hanessian7 described an enantioselective synthesis of (+)-1 by the "chiron approach" in which the two vicinal viny1 and carboxymethyl groups are efficiently introduced utilizing a chirai template derived from D-glucose.