A concise synthesis of tetrabenazine: an intramolecular aza-Prins-type cyclization via oxidative C-H activation

A concise synthesis of tetrabenazine and dihydrotetrabenazine is described. The key feature of this synthesis is the intramolecular aza-Prins-type cyclization of an amino allylsilane via oxidative C-H activation.     

A facile synthesis of 2-methylquinolines via Pd-catalyzed aza-wacker oxidative cyclization

A novel Pd-catalyzed Wacker-type oxidative cyclization under air is described. By using this cyclization, a series of 2-methylquinolines are readily prepared with good yields under mild conditions.     

Highly stereocontrolled synthesis of fluorinated 2,6-trans dihydropyrans via Prins cyclization

A highly efficient method for the synthesis of fluorinated 2,6-trans dihydropyrans via BF₃·Et₂O-promoted Prins cyclization of allenic alcohols and aldehydes is developed. Various 2,6-trans fluorodihydropyrans are obtained in moderate to good yields with excellent diastereoselectivities.     

A rapid enantiospecific synthesis of the (6,6,5)-tricyclic ring system of the elisabethane diterpenes

A rapid enantiospecific stereoselective synthesis of the 6,6,5-ring system of the novel tricyclic elisabethin diterpenes, starting from (R)-carvone, employing a ROM-RCM sequence as the key step, has been accomplished.     

A general approach to cyathin diterpenes. Total synthesis of allocyathin B(3)

[reaction: see text] The synthesis of allocyathin B(3) from an advanced intermediate possessing the ring system and relative stereochemistry but lacking the isopropyl and hydroxymethyl groups is reported. The isopropyl group was introduced by radical cyclization of a methyl propargyl acetal of an alpha-bromo ketone, and the hydroxymethyl group was generated by Pd-catalyzed carbonylation of a vinyl triflate. The route provides functionalized intermediates that could allow access to more complex members of the cyathin family of diterpenes.     

Total synthesis of debromoflustramine B via biomimetic alkylative cyclization

[reaction: see text] The hexahydropyrrolo[2,3-b]indoline skeleton is readily accessed by the zinc triflate-mediated alkylation of tryptamine derivatives. The methodology was employed in a three-step total synthesis of debromoflustramine B.     

Studies directed toward the synthesis of hamigeran B: a catalytic oxidative cyclization

An approach to the synthesis of hamigeran B is described. Key steps include a Tius-Nazarov cyclization and a palladium-catalyzed oxidative cyclization of an α-hydroxyenone.     

Synthetic approach toward the total synthesis of kempane diterpenes via transannular Diels-Alder strategy

Total syntheses of two new (+/-)-kempane derivatives 30 and 47 were achieved with transannular Diels-Alder reaction (TADA) serving as the key step for the stereoselective formation of tricyclic [6.6.5] system 3. This synthetic approach also reveals that the geometry of the C3 group of such a tricyclic system plays an important role for the formation of the seven-membered kempane skeleton.     

Total synthesis of flocoumafen via knoevenagel condensation and intramolecular ring cyclization: general access to natural products

The total synthesis and structure determination of cis- and trans-flocoumafen was described. The key synthetic steps involve Knoevenagel condensation with p-methoxybenzaldehyde, in situ decarboxylation and intramolecular ring cyclization to construct the tetralone skeleton. Stereospecific reduction of the O-alkylated ketone 13 afforded good yield of precusor alcohol 5. Final coupling of alcohol 5 with 4-hydroxy-coumarin yielded flocoumafen (1). Separation and structure determination of cis- and trans-flocoumafen through 2D NMR analyses-assisted computer simulation techniques for the evaluation of anticoagulant activities are reported for the first time. This method is useful for generating the core tetralone skeleton of 4-hydroxycoumarin derivatives and provides a generalized access to various warfarin type anticoagulants.     

Anionic cyclization approach toward perhydrobenzofuranone: stereocontrolled synthesis of the hexahydrobenzofuran subunit of avermectin

A facile anionic cyclization approach toward stereocontrolled synthesis of the hexahydrobenzofuran subunit 3 of avermectin is described. As a model study, treatment of iodo compound 7 with n-BuLi at -100 degrees C effected metal-halogen exchange and subsequent anionic cyclization to afford perhydrobenzofuranone 8. For the total synthesis of subunit 3, compound 9 was dihydroxylated to give diol 10. Protection of the hydroxyl groups of diol 10 gave compound 11. Ketone 11 was then converted into the required enone 12 using Saegusa's protocol. On iodination followed by Luche reduction, enone 12 yielded alpha-iodo allylic alcohol 14, which on alkylation afforded ether 15. Conversion of the ester unit of 15 into a Weinreb amide group followed by anionic cyclization gave enone 17. 1,4-Addition of (MeOCH(2))(2)CuCNLi(2) to enone 17 followed by cleavage of the acetal unit afforded ketone 19. Preferential acetylation of the secondary alcoholic function of 19 afforded compound 20. The stereochemistry of 20 is confirmed by single-crystal X-ray analysis. Elimination of HOAc from 20 gave the crucial olefin 21. Hydrolysis of the acetate unit of 21 followed by protection of the resulting alcoholic function yielded tert-butyldimethylsilyl ether 23. Introduction of a hydroxyl group at the ring junction of 23, using Davis's procedure, finally afforded the hexahydrobenzofuran subunit 3.     

Total synthesis of (±)-lantalucratins A and B by CAN-mediated oxidative cyclization

The first total synthesis of (±)-lantalucratins A and B is described. Introduction of an alkyl side chain at the 6-position was proceeded by directed ortho-lithiation and subsequent alkylation reaction to afford 6-alkyl-5,7,8-trimethoxy-1-naphthol as a synthetically important intermediate for (±)-lantalucratins A and B in excellent yield with complete regioselectivity. The 1,2-naphthoquinone fused five-membered cyclic ether framework was constructed directly from 3-hydroxyalkyl-naphthalenes by oxidative intramolecular cyclization reaction with diammonium cerium(IV) nitrate. (±)-Lantalucratins A and B were obtained in 69% and 45% overall yields, respectively.     

Radical oxidative cyclization of spiroacetals to bis-spiroacetals: an overview

The use of iodobenzene diacetate and iodine under photolytic conditions provides and efficient method for the oxidative cyclization of spiroacetals bearing an hydroxyalkyl side chain to bis-spiroacetals. An overview is provided of the use of this reaction for the synthesis of several bis-spiroacetal containing natural products such as the polyether antibiotics salinomycin and CP44,161 and the shellfish toxins, the spirolides.     

A general,stereocontrolled entry to pyrimidine homo-C-nucleosides

A simple synthesis of nucleoside analogues with a methylene group between the ribose and 5-position of pyrimidine appendages is outlined.     

Total synthesis of ionophores the monensin BC-rings via permanganate promoted stereospecific oxidative cyclization

Complex tetrahydrofuran 8, containing the elements of the BC-rings of monensin with four chiral centers, and functionalized for further elaboration, is synthesized via permanganate promoted stereospecific oxidative cyclization of an acyclic, achiral 1,5-diene precursor.     

Facile one-pot synthesis of N-fused 1,2,4-triazoles via oxidative cyclization using manganese dioxide

Chemistry of Heterocyclic Compounds - A facile one-pot synthesis of N-fused 1,2,4-triazoles from heterocyclic hydrazines and aldehydes is reported. The reaction is efficiently promoted by manganese...     

Intramolecular dials-alder cyclization of N-furfurylpropargylamines: A novel general synthesis of isoindoles

Benzotriazole mediated synthesis from furfurylamines, aldehydes and lithium acetylides readily provides high yields of N-furfurylpropargylamines. These undergo intramolecular Diels-Alder cyclization to give isoin-doles, which are characterized as their Diels-Alder reaction products with dimethyl acetylenedicarboxylate.