An intramolecular Tsuji-Trost reaction based approach to the synthesis of 6-methylene indolizidines

Herein we describe the efficient stereoselective preparation of C8 substituted indolizidines bearing a 6-methylene group, from the chiral pool starting material l-proline. This synthesis, employing a Tsuji-Trost reaction as the key step, represents a potentially, efficient route to pumiliotoxin natural product epimers.     

Revisiting a classic approach to the Aspidosperma alkaloids: an intramolecular Schmidt reaction mediated synthesis of (+)-aspidospermidine

[reaction: see text] A total synthesis of (+)-aspidospermidine (1) is described. The key reactions used in the synthesis of this pentacyclic Aspidosperma alkaloid were a deracemizing imine alkylation/Robinson annulation sequence, a selective "redox ketalization", and an intramolecular Schmidt reaction. A Fischer indolization step carried out on a tricyclic ketone mirrored the sequence reported by Stork and Dolfini in their classic aspidospermine synthesis.     

Enantioselective synthesis of bicarbocyclic structures with an all-carbon quaternary stereocenter through sequential cross metathesis and intramolecular Rauhut-Currier reaction

A new extension of the Birch-Cope sequence is described which allows the efficient enantioselective construction of highly functionalized, fused bicarbocyclic structures with an all-carbon quaternary stereocenter in two steps. The two-step sequence includes a cross metathesis between a terminal alkene and a polarized alkene followed by an intramolecular Rauhut-Currier reaction with a trialkylphosphine catalyst.     

Construction of quaternary centres for natural polycycles: The Pauson-Khand approach

Construction of quaternary carbons is a challenge in PK chemistry, with few precedents in the literature. Starting from suitable functionalized enynes including an aromatic ring that templates the reaction, polycyclic ketones are obtained with a quaternary carbon. Special reaction conditions are necessary including the use of molecular sieves and co-catalysis with rhodium complexes jointly with cobalt carbonyl. The products obtained are intermediates in the synthesis of various natural products like the Hamigeran family and the steroidic alkaloid Conessine.     

An intramolecular Diels-Alder approach to the eunicelins: enantioselective total synthesis of ophirin B

The enantioselective synthesis of the eunicellin ophirin B has been completed. A ring-closing metathesis provides efficient access to the oxonene ring, and a highly diastereoselective intramolecular Diels-Alder reaction results in the formation of the hydrobenzofuran portion of the molecule.     

Asymmetric synthesis of 3,5-disubstituted indolizidines by intermolecular addition of an allylsilane on an N-acyliminium ion

A diastereoselective synthesis of 3,5-disubstituted indolizidines based on an intermolecular addition of an allylsilane on an acyliminium ion derived from (S)-pyroglutamic acid is described. The synthetic potential of this methodology is demonstrated by the enantioselective synthesis of (−)-indolizidine 195B, (−)-indolizidine 223AB, (+)-monomorine and (−)-3-butyl-5-propyl indolizidine.     

An efficient synthesis of 4-bromo-N-substituted oxindoles by an intramolecular copper-catalyzed amidation reaction

A highly efficient synthetic approach to novel 4-bromo-N-substituted oxindoles is described. The method involves a mild intramolecular copper-catalyzed amidation reaction of N-substituted 2,6-dibromophenylacetamides. In contrast to our recently published palladium-catalyzed amidation reaction, no concomitant dimerization on the 3-position of the formed oxindole occurs.     

A facile three-step synthesis of (±)-crispine A via an acyliminium ion cyclisation

A high yielding cyclisation of the readily available N-(4,4-diethoxybutyl)-2-(3,4-dimethoxyphenyl)acetamide to 8,9-bis(methyloxy)-2,3,6,10b-tetrahydropyrrolo[2,1-a]isoquinolin-5(1H)-one is described. The latter can be reduced with either AlH₃ or BH₃ to (±)-crispine A in an overall yield of 55%.     

Biomimetic approach to perophoramidine and communesin via an intramolecular cyclopropanation reaction

[reaction: see text] Starting from tryptamine 4 and isatin 5, a biomimetic approach to the pentacyclic substructure 1 of perophoramidine and communesin was developed. The key steps were to create a stable three/six bicyclic system 2 on the 2,3-double bond of an indole derivative 3 by an intramolecular cyclopropanation, followed by ring opening of the resulting cyclopropane ring with the in situ generated amine group of an aniline.     

An approach to triquinane synthesis using the Pauson-Khand reaction

Tricyclic skeletons have been generated from acyclic enyne precursors by using an intramolecular Pauson-Khand reaction in combination with aldol, Michael and alkylation reactions.     

An efficient carbapenem synthesis via an intramolecular Wittig reaction of new trialkoxyphosphorane-thiolesters

New trialkoxyphosphorane-thiolesters 10, obtained by reaction of oxalimides 9 with trialkyl phosphite, were efficiently cyclized by an intramolecular Wittig reaction to give carbapenems 11.     

An efficient approach towards three component coupling of one pot reaction for synthesis of functionalized benzopyrans

Three component coupling of one pot reaction which servers as the most convenient route to the synthesis of benzopyran derivatives using the TiCl₄ catalyst (10 mol %) under solvent free conditions is described. The procedure offers a systematic method with a number of advantages including operational simplicity, neat reactions, reduced reaction time, high yields of products and applicability to large scale reactions.     

Regiocontrol in an intramolecular Schmidt reaction: total synthesis of (+)-aspidospermidine

[reaction--see text] A total synthesis of (+)-aspidospermidine (1) is described, featuring an intramolecular Schmidt reaction as the key step. The effects of stereochemistry and protecting group status on the regio- and chemoselectivity of this reaction were examined.     

Enantioselective formation of quaternary stereocenters using the catalytic intramolecular Stetter reaction

Asymmetric formation of quaternary stereocenters has been accomplished using the catalytic intramolecular Stetter reaction. A variety of tethered aldehydes and Michael acceptors are cyclized in excellent yields and enantioselectivities.     

SN2 vs. E2 on quaternary centres: an application to the synthesis of enantiopure beta2,2-amino acids

S(N)2 and E2 competing reactions in cyclic sulfamidates can be modulated by the change of an amide group to an ester group attached to the quaternary carbon activated for the nucleophilic attack, allowing an easy approach to enantiopure alpha,alpha-disubstituted beta-amino acids.     

The intramolecular tandem Michael/Mannich-type reaction of α,β-unsaturated carbonyl compounds with acyliminium ions provides access to chiral indolizidines

The intramolecular tandem Michael/Mannich-type (Michael addition/halo-Mannich-type) reaction using TiCl₄/n-Bu₄NI system between the α,β-unsaturated carbonyl compounds possessing an Evans oxazolidinone as a chiral auxiliary and N-acyliminium ion intermediates is described. The reaction was promoted in a mixed solvent of AcOEt–CH₂Cl₂ to afford indolizidine compounds with three stereogenic centers.     

An intramolecular Schmidt reaction strategy for the synthesis of a methyl analogue of crispine A

A convenient approach for the synthesis of a methyl analogue of crispine A, a potent anticancer agent, through intramolecular Schmidt reaction of azido-ketone 6 is described.     

Pd-catalyzed intramolecular Heck reaction for the synthesis of 2-methylbenzofurans

A new strategy for the synthesis of 2-Methylbenzofurans via the intramolecular Heck reaction has been developed. This efficient palladium-catalyzed system showed good catalytic activity. Various substituted 2-methylbenzofurans could be afforded in good to excellent yields.     

Carbenium ion trapping using sulfonamides: an acid-catalysed synthesis of pyrrolidines by intramolecular hydroamination

Cyclisations of homoallylic sulfonamides proceed smoothly via carbenium ion generation using trifluoromethanesulfonic (triflic) acid, the ease of cyclisation being directly related to the ion stability to give good to excellent yields of the corresponding pyrrolidines. Both toluene- and nitrophenyl-sulfonyl groups are suitable for all substrates tested whereas the corresponding carbamates are only useful in cases of tertiary and highly stabilised carbenium ions. Polyene-derived sulfonamides can also be cyclised to the corresponding polycyclic systems in remarkably high yields, in reactions reminiscent of related cascades encountered in terpene biosynthesis.     

Remote asymmetric induction in an intramolecular ionic Diels-Alder reaction: application to the total synthesis of (+)-dihydrocompactin

The total synthesis of (+)-dihydrocompactin via an intramolecular ionic Diels-Alder reaction that proceeds with remote stereocontrol is described. This reaction proceeds by an intermediate vinyl-oxocarbenium ion (6), the conformational constraints of which lead to the observed asymmetric induction. The sense of asymmetric induction appears contrasteric and is explained by the proposed reactive conformation shown in Figure 1.