Tandem Reaction Sequence Research Articles

Total synthesis of panepophenanthrin.

[reaction: see text] The biomimetic synthesis of the racemic dimer panepophenanthrin was achieved in good yield employing a tandem reaction sequence.

Synthesis of α‐C‐Glycosides via Tandem Tebbe Methylenation and Claisen Rearrangement.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of α- C-glycosides via tandem Tebbe methylenation and Claisen rearrangement

A variety of α- C-glycosides may be accessed in an entirely stereoselective fashion from 3-OH glycal esters, by way of the tandem reaction sequence of Tebbe methylenation and Claisen rearrangement. In contrast with previous studies in the corresponding β-series, careful control of conditions for Claisen rearrangement is required in order to avoid loss of integrity of anomeric stereochemistry; thermal rearrangements are best carried out in xylene in a sealed tube.

Stereoselective synthesis of C-glycosides from carboxylic acids: the tandem Tebbe-Claisen approach.

A variety of beta- or alpha-C-glycosides may be readily accessed in an entirely stereoselective fashion from esters derived from the reaction of carboxylic acids and 3-hydroxy glycals, by way of a tandem reaction sequence of Tebbe methylenation and Claisen rearrangement. Though of wide scope, for example allowing the synthesis of 1-6 linked C-disaccharides, the methodology does not currently allow the synthesis of C-glycosyl alpha-amino acids.

Total synthesis of (+)-aspidospermidine: a new strategy for the enantiospecific synthesis of aspidosperma alkaloids.

A new strategy was developed for the enantiospecific synthesis of aspidosperma alkaloids. The key steps involve a novel ketene-lactonization reaction of a chiral vinyl sulfoxide to efficiently set up the quaternary carbon center, and a tandem Michael addition-alkylation reaction sequence to form the polycyclic core structure. This new strategy was employed in the total synthesis of natural product (+)-aspidospermidine.

Synthesis of polycyclic polyfunctionalized carbocycles by a cobalt(I)‐initiated tandem diels–alder reaction sequence

AbstractThe cobalt(I)‐catalyzed neutral Diels–Alder reaction of acyclic 1,3‐dienes with conjugated enynes can be used to generate secondary dihydroaromatic 1,4,8‐trienes containing a 1,3‐diene substructure, in good yields under mild reaction conditions. These 1,3‐dienes can be converted, with reactive dienophiles in a tandem normal Diels–Alder reaction, into polycyclic compounds. In a similar tandem Diels–Alder sequence, the cobalt‐catalyzed neutral homo Diels–Alder reaction of 2,5‐norbornadiene can be used to generate polycyclic cycloaddition adducts. A sequential triple Diels–Alder reaction sequence can be realized when norbornadiene is reacted with the excess of the conjugated enynes under cobalt(I) catalysis. In a homo Diels–Alder, neutral Diels–Alder, normal Diels–Alder reaction sequence, the intermediately formed adducts are reacted with activated dienophiles to yield polycyclic compounds in a short sequence. The structures of several products were established by X‐ray analysis. This showed that predominantly endo‐products are formed in the tandem reaction sequences, while the exo‐product becomes predominant in the triple Diels–Alder reaction sequence.

Dimetalation of Pyrazines. A One-Pot Synthesis of Multisubstituted Pyrazine C-Nucleosides

As a part of our efforts to pursue direct, convergent, and concise methodologies for the synthesis of pyrazine C-nucleosides, we have successfully established a sequential dilithiation-addition method, which allows one to introduce two different functional groups to a pyrazine ring in a one-pot fashion. 2,6-Dichloropyrazine was dilithiated at -100 degrees C and then allowed to react with an electrophile, such as bromine, iodine, or disulfides, followed by a reaction with a protected ribonolactone to afford C-nucleosides. After reduction and deprotection, tetrasubstituted pyrazine C-nucleosides, including 2,6-dichloro-3-iodo-5-(beta-D-ribofuranosyl)pyrazine and 2-bromo-3,5-dichloro-6-(beta-D-ribofuranosyl)pyrazine, were obtained. A tandem reaction sequence occurred when disulfides were used, resulting in the formation of 5,6-bis-methylthio-2-chloro-3-(beta-D-ribofuranosyl)pyrazine and 6-(beta-D-ribofuranosyl)-2,3,5-tris-phenylthiopyrazine.

Synthesis of Polycyclic Polyfunctionalized Carbocycles by a Cobalt(I)-Initiated Tandem Diels-Alder Reaction Sequence

Synthesis of Polycyclic Polyfunctionalized Carbocycles by a Cobalt(I)-Initiated Tandem Diels-Alder Reaction Sequence

Palladium-catalyzed coupling of vinylogous amides with aryl halides: applications to the synthesis of heterocycles

[formula: see text] Described herein is the first example of the palladium-catalyzed coupling of vinylogous amides with aryl bromides and chlorides. The scope of this reaction with respect to the aryl component is investigated. Additionally, a tandem reaction sequence in which the above coupling is followed by an intramolecular Heck reaction is presented. These reactions can be applied to high-yielding, one-pot syntheses of nitrogen-containing heterocycles.

Tandem Reaction Sequences under Hydroformylation Conditions: New Synthetic Applications of Transition Metal Catalysis

Tandem Reaction Sequences under Hydroformylation Conditions: New Synthetic Applications of Transition Metal Catalysis

The Synthesis of Carboxylic Acids via an Aldol-Grob Reaction Sequence

Ketones react with aromatic aldehydes via a tandem Aldol-Grob reaction sequence. The reaction, initiated by boron trifluoride, produces a carboxylic acid fragment and can serve as an alternative to the Baeyer-Villiger reaction.

A new tandem route to angular tetraquinanes. Synthesis of the Waihoensene ring system.

[formula: see text] This paper describes a new tandem reaction sequence leading to angularly fused polyquinanes from squaric acid-derived bicyclo[6.3.0]-undecadienediones. Such compounds undergo a dual Michael addition. The enolate form in the first intermolecular addition undergoes the second intramolecular transannular addition to give the angular polyquinanes. A particularly interesting example is a catalytic transformation of cis-13-methylyricyclo[10.3.0.0]pentadeca-4(5),12(13)-diene-3 ,14-dione to (3R*,3aS*,5aR*,9aR*,11aR*)-3-methyl-1,2,3,5,5a,6 ,7,10,11,11a-decahydro-4H- pentaleno[6a,1-c]indene-2,10-dione, a compound having the tetracyclic ring system found in the natural product waihoensene. The mechanism and synthetic scope of these reactions are discussed.

On the Behavior of 5,8-Bis(trimethylsilyl)cycloocta-1,3,6-triene in Cycloaddition Reactions and Subsequent Chemistry

Phosphaalkynes 2 and electron-deficient alkynes 11 readily react in a [4 + 2] cycloaddition process with 5,8-bis(trimethylsilyl)cycloocta-1,3,6-triene (8) in its bicyclic form 10 to furnish regioselectively the tricyclodecadienes 12 and 13, respectively. The phosphorus-containing compounds 12 exhibit structural features which make them suitable for homo-Diels–Alder reactions with electron-deficient acetylenes. A single crystal structure analysis of the homo-Diels–Alder adduct 14b confirmed the structure and relative configuration of the phophatricyclodecadienes 12. In solution the tricyclodecadienes 13 are prone to facile cycloreversion yielding the phthalic esters 15 and the cyclobutene 16. The latter is rapidly converted into the corresponding 1,3-butadiene 18, which can be trapped in a Diels–Alder/phospha-ene/Diels–Alder tandem reaction sequence by phosphaalkyne 2a. The phosphatricyclodecadiene 12 is thermally more stable; loss of cyclobutene 16 only occurs under FVP conditions to afford the λ3-phosphinine 22.

A tandem Aldol-Grob reaction of ketones with aromatic aldehydes

Aromatic aldehydes react with ketones to produce(E)-1-aryl-1-alkenes via a tandem Aldol-Grob cleavage reaction sequence. The reaction, initiated by boron trifluoride, also produces a carboxylic acid fragment. Aromatic aldehydes react with ketones in the presence of boron trifluoride to produce(E)-1-aryl-1-alkenes via a tandem Aldol-Grob cleavage reaction sequence. [Display omitted]

CycloSal-2',3'-dideoxy-2',3'-didehydrothymidine monophosphate (cycloSal-d4TMP): synthesis and antiviral evaluation of a new d4TMP delivery system.

The synthesis, hydrolysis, and antiviral evaluation of novel, lipophilic cycloSal-d4TMP derivatives 3a-h of the anti-HIV dideoxynucleoside 2',3'-dideoxy-2',3'-didehydrothymidine (d4T, 1) are reported. This pro-nucleotide concept has been designed to deliver d4TMP (2) by selective chemical hydrolysis. All compounds 3a-h were synthesized using phosphorus(III) chemistry in good yields and in somewhat lower yields using phosphorus(V) chemistry starting from substituted salicyl alcohols 6a-h. The phosphotriesters 3 were obtained without stereochemical preference with respect to the configuration at the phosphorus center as 1:1 diastereomeric mixtures. However, a few of the triesters 3 could be separated into the diastereomers by means of semipreparative HPLC. In a 1-octanol/phosphate buffer mixture, all compounds 3 exhibited 9-100-fold higher lipophilicity as judged from their Pa values as compared to d4T (1). Furthermore, in hydrolysis studies 3 decomposed under mild aqueous basic conditions releasing solely d4TMP (2) and the diols 6 following the designed tandem reaction sequence. A correlation of the electronic properties introduced by the substituents and the half-lives of triesters 3 was observed. Thus, by varying the substituent, the half-lives of 3 could be adjusted over a wide range of compounds still delivering d4TMP (2) selectively. Phosphotriesters 3 exhibited considerable activity against HIV-1 and HIV-2 in wild-type human T-lymphocyte (CEM/O) cells as well as mutant thymidine kinase-deficient (CEM/TK-) cells. Surprisingly, we observed a 3-80-fold difference in antiviral activity between the two diastereomers. Our data clearly prove that the cycloSal-d4TMPs deliver exclusively the nucleotide d4TMP not only under simulated hydrolysis conditions but also under cellular conditions and thus fulfill the thymidine kinase-bypass premise. Therefore, the cycloSal-nucleotide concept is the first reported pro-nucleotide system that delivers the dideoxynucleotide by a pH-driven, chemically activated, tandem reaction without the requirement of an enzymatic contribution.

A,B-Diheteropentalenes by a Tandem Intramolecular Diels-Alder/Reverse Diels-Alder Reaction Sequence. Application to the Synthesis of Thieno[3,4-b]furan

Alkylation of 2-furylmethanethiol (28) with propargyl chloride gave the thioether (22) which on methoxycarbonylation afforded the acetylenic ester (30). On heating, this material underwent an intramolecular Diels -Alder reaction to give the tricyclic compound (32). In the presence of 3,6- di (pyridin-2′-yl)-s- tetrazine , (32) afforded methyl 4,6-dihydrothieno[3,4-b]furan-3-carboxylate (38) by a sequence involving a further Diels -Alder reaction followed by two reverse Diels-Alder reactions. The ester (38) could be dehydrogenated to give methyl thieno [3,4-b]furan-3-carboxylate (40) while hydrolysis of (38), followed by decarboxylation and dehydrogenation delivered the parent thieno [3,4-b]furan (5). 3-Methyl-4,6-dihydrothieno[3,4-b]furan (46) and 3-methylthieno[3,4-b]furan (47) were prepared; a comparison of the 4JMe-C=C-H coupling constants in the 1H n.m.r . spectra of (46) and (47) suggests that an increase in the C2-C3 furyl bond order accompanies the (46) → (47) conversion. Methyl 4,6-dihydrofuro[3,4-b]furan-3-carboxylate (39), 4,6-dihydrofuro[3,4-b]furan (27) and methyl 4,6-dihydro-6-phenylfuro[3,4-b]furan-3-carboxylate (53) were prepared by an analogous tandem reaction sequence. These compounds could not be dehydrogenated to the fully conjugated furo [3,4-b]furan ring system.

Synthesis of polycyclic cyclobutane derivatives by tandem intramolecular Michael-aldol reaction under two complementary conditions: TBDMSOTf-Et3N and TMSI-(TMS)2NH

The treatment of α,β-unsaturated esters having a ketone function at an appropriate position with either TBDMSOTf in the presence of Et 3 N or TMSI in the presence of (TMS) 2 NH provided, via a tandem intramolecular Michael-aldol reaction sequence, several different types of cyclobutane derivatives. The two reaction conditions were complementary. Tricyclo[4.2.1.03-8]nonanes 34 and 35, tricyclo[5.1.1.0 3,8 ]nonane 40, tricyclo[5.4.0.0 3,7 ]undecane 51, tetracyclo[5.4.0.0 3,7 .0 9,11 ]undecane 45, and the bicyclo[3.2.0]heptanes 36, 57, and 38, which have structures either partially or completely similar to those of endiandric acids A (1a), B (1b), and C (2), trihydroxydecipiadiene (3), lintenone (4), italicene (3), and filifolone (6), were stereoselectively synthesized by the tandem reaction

An intramolecular cyclization approach to optically active cyclopentenyl bromides

The two antipodes of 1-bromo-3,3-dimethyl-4-[(tert-butyldimethylsilyl)oxy] cyclopentene, the dextrorotatory form of which (1) is regarded as a potential synthetic precursor to kalmanol, have been prepared in a state of high enantiomeric purity from propargyl alcohol. The key steps in the abbreviated synthetic pathway involve the bromination-dehydrobromination of 3-(trimethylsilyl)propenal 12 to give 2-bromo-3-(trimethylsilyl)propenal 7, the conversion of 2-bromo-3-(trimethylsilyl)propen-1-ol 13 to the 1-bromo-3,3-dimethylcyclopenten-4-ol 18 by a novel tandem Claisen-Sakurai reaction sequence, and efficient enzymatic resolution of 18 via its chloroacetate ester. The absolute configurational assignments are based on 1 H NMR analyses of the (R)- and (S)-MTPA esters of (-)-20

Novel tandem rearrangement of a steroidal ring Dcycloadduct derived from 2-chloroacrylonitrile

The cycloadduct 2 derived from reaction of 3-methoxyestra-1,3,5(10), 14, 16-pentaen-17-yl acetate 1 with 2-chloroacrylonitrile undergoes a tandem reaction sequence in the presence of alkali, leading to (161R)-3-methoxy-17-oxo-15β, 161-cyclo-14, 16β-ethano-14β-estra-1,3,5(10)-triene-161-carbonitrile 4, the X-ray crystal structure of which is reported; compound 4 is converted into new ring D bridged analogues of estrone.

1,3-Oxazolidin-2-ones from 1H-aziridines by a novel stratagem which mimics the direct insertion of CO2

N-Ethoxycarbonylaziridines 2 undergo smooth thermal transformation into 1,3-oxazolidin-2-ones 3 on flash pyrolysis by a tandem reaction sequence equivalent to direct insertion of CO2 into the parent 1H-aziridine.