Cyclizations hexafluorophosphate

Cyclization takes place when tert-butylisocyanide, benzaldehyde, anilinium chloride, and carbonyl(dicyano)cyclopentadienyl ferrate are reacted, the carbene complex 42 being the result (95JOM(491)135). /50-butyraldehyde, tert-butyl isocyanide, ammonium hexafluorophosphate, and [(T -Cp)Fe(CO)(CN)2] give the cationic bis-carbene 43. 

The iron-mediated synthesis of 2-oxygenated carbazole alkaloids is limited and provides only a moderate yield (11%) for the oxidative cyclization to 2-methoxy-3-methylcarbazole using iodine in pyridine as the reagent [90]. Ferricenium hexafluorophosphate is the superior reagent for the iron-mediated arylamine cyclization leading to 3-oxygenated carbazoles (Scheme 12). Electrophilic substitution of the arylamines 16 with the complex salt 6a leads to the iron complexes 17. Oxidative cyclization of the complexes 17 with an excess of ferricenium hexafluorophosphate in the presence of sodium carbonate affords... 

With respect to photoinitiation, generally, it is important to be very careful in one s choice of sensitizers. For example, attempts to initiate the cyclization of homobenzylic ethers failed if 1,4-dicyanobenzene was used as a sensitizer. Rapid regeneration of the starting material by back-electron transfer from the dicyanobenzene anion-radical to the substrate cation-radical was the cause of cyclization inefficiency. To slow this unproductive process, a mixture of A-methylquinolinium hexafluorophosphate (sensitizer), solid sodium acetate (buffer), and tert-butylbenzene (cosensitizer) in 1,2-dichloroethane was employed. This dramatically increased the efficiency of the reaction, providing cyclic product yields of more than 90% in only 20 min (Kumar and Floreancig 2001, Floreancig 2007). 

Alternatively, using the iron-mediated arylamine cyclization, a short access to carazostatin (247), albeit in lower yield, was achieved. The oxidation of the complex 714 with ferricenium hexafluorophosphate in the presence of sodium carbonate... 

An alternative method for the oxidative cyclization of the arylamine-substituted tricarbonyl(r -cyclohexa-l,3-diene)iron complex (725) is the iron-mediated arylamine cyclization. Using ferricenium hexafluorophosphate in the presence of sodium carbonate provided hyellazole (245) directly, along with the complex 727, which was also converted to the natural product (599,600) (Scheme 5.71). 

Electrophilic iodine reagents have also been employed in iodocyclization. Several salts of pyridine complexes with I+ such as bis(pyiidinium)iodonium tetrafluoroborate and bis(collidine)iodonium hexafluorophosphate have proven especially effective.61 y-Hydroxy- and d-hydroxyalkcncs can be cyclized to tetrahydrofuran and tetrahydropyran derivatives, respectively, by positive halogen reagents.62 (see entries 6 and 8 in Scheme... 

Formation of 1,3-dioxanes was also effected by intramolecular cyclization of suitable precursors possessing a double bond either two or three carbons away from the oxygen functional group. For example, /3-trimethylsilylethoxymethyl (SEMI-protected allylic alcohols reacted with bromonium dicollidine hexafluorophosphate (BrDCH) to 5-bromo-l,3-dioxanes in acceptable yields and with a high preference for the 4,6-tfr-addition product (Equation 83) <2000JCX32797>. 

An intramolecular substitution of trimethylamine fix>m 17 gave a bicyclic oxetane 18 in a diastereoselective process <98MI2185>. A [2+2]cycloaddition of 2,2,4,5-tetrasubstituted 2,3-dihydrofuran to aryl aldehydes gave the bicyclic oxetane 19 <98JCS(P1)3261>. 2,2-Disubstituted-3-bromooxetane was obtained by a 4-endo-tcig cyclization process of 3,3 -disubstituted allyl alcohol in the presence of bis(collidine)bromine hexafluorophosphate <99JOC81>. 

Cinnamyl alcohols such as 95 were converted to the corresponding oxetane 96 by reaction with bis-(collidine)bromine(l) hexafluorophosphate (Equation 32) via a 4- r/o-/r7g-electrophilic cyclization <1999JOC81, 2001TL2477>. High yields of oxetanes (up to 88%) were only achieved with tertiary alcohols, with secondary alcohols giving mainly degradation products. 

Gevorgyan et al. also observed alkyl migration while studying the cyclization of substituted allenones in the presence of various metal salts. While again not the best catalysts, silver hexafluorophosphate or triflate could be used in toluene or dichlor-omethane, giving substituted furans in high yields (Scheme 3.56).84... 

A new synthetic pathway for the construction of cyclic acetals (41) from homobenzylic ethers (40) has been recently developed by Floreancig et al. [44]. The electron transfer initiated oxidative cyclization is efficiently catalyzed by A-methylquinolinium hexafluorophosphate (NMQPE6) in the presence of oxygen (Sch. 22). For gram-scale preparations solid Na2S203 has to be used as an additive to suppress decomposition caused by the reactive oxygen species involved. 

There are only two reports of electrophilic attack on aromatic oxathioles. The cyclization of (62) in TFA generates the 1,3-oxathiolium (63), which cannot be isolated as such but which suffers acylation to give the stable derivative (64). It is unclear whether the nitrosation of thiapentalene (65) represents an electrophilic attack on the intact system or whether attack occurs on the ring-opened species (66). In the event, nitrosyl hexafluorophosphate... 

The 7-octen-l-ols substituted with a rigid cyclic moiety (cyclopropane or phenyl) react with bis(collidine)iodonium and -bromonium hexafluorophosphates to afford oxocanes in modest to good yields (Scheme 12). If the cyclic component is an oxirane or a dioxolane ring, the yields are lower. The cyclizations are carried out in dichloromethane (DCM) at room temperature <2003EJ0463>. 

The bis(ry/ -collidine)iodine(l)hexafluorophosphate-promoted cyclization of unsaturated hydroperoxide 264 provided an excellent method for the production of the perhydro-dioxocin 265 in good yield (Equation 19) <2003T525>. 

The studies of the linkage isomers of the bis(thioimidazolyl)methane family reported the cyclization of the chloromethylthioimidazole 148 into the unstable ionic dithiadiazocine chloride 149 (mp 224 °C, dec.) which was converted into the stable hexafluorophosphate 150 (mp 234 °C, dec.) (Scheme 14) <2005JOC8755>. The dication 150 was characterized by single-crystal X-ray diffraction and was shown to have a chair conformation. Electrochemical studies of the salt 150 in acetonitrile showed an irreversible reduction wave centered at —1.09 V <2005JOC8755>. 

Hydride abstraction from dienyl tricarbonyl iron complexes furnishes cationic dienyl tricarbonyl iron complexes. For example, reaction of the diene-iron tricarbonyl complex (115) with triphenyhnethyl hexafluorophosphate followed by trimethylsilyl cyanide furnished with excellent regio- and stereoselectivity a new diene iron tricarbonyl complex (116) (Scheme 170). Excellent regio- and stereoselectivity is seen upon reaction of the cationic complex (116) with trimethylsilyl cyanide (TMS-CN) (Scheme 170). Reduction of the nitrile affords a spirocyclic lactam complex. Intramolecular cyclization of in situ formed enols furnishes spirocyclic compounds again with excellent stereoconfrol (Scheme 171). An interesting example of hydride transfer from a cyclohexadiene ring to a pendant aldehyde followed by nucleophilic addition is seen in Scheme 172. 

Stoddart s extensive work on catenanes started with the realization that diben-zocrown ethers contained two environments, the polyether electron-donor region and the electron-rich region with 7r-stacking potential. The aromatic regions were used to hold a 4,4/-bipyridinium-based molecular clip in place while cyclization with 1,4-di(bromomethyl)benzene was effected. The interlocked complex was obtained in 70 percent yield as the tetracationic salt with hexafluorophosphate counterions [4]. 

Complexes of chlorobenzenes with iron (cyclopentadienyl)hexafluorophosphate have useful reactivities, for example, in cyclization. The complex (28.7) is cyciized with hydrazine to a dihydrocinnoline complex the metallophosphate is removed and the ring is aromatized by sodamide. 

Meutermans and Alewood [48] reported the solid-phase synthesis of tetrahydroisoquinolines 13 and dihydroisoquinolines 13a using the Bischler-Napieralski reaction (Fig. 5). The polystyrene resin-bound deprotected L-3,4-dimethoxyphenylalanine was acylated with acetic acid derivatives using N- [(IH-benzotriazol-1 -yl)(dimethylamino)methylene] -iV-methylmethana-minium hexafluorophosphate A-oxide (HBTU) as a coupling reagent. The product obtained was then treated with phosphorus oxychloride under optimized conditions to afford a Bischler-Napieralski cyclization. Hutchins and Chapman [49] reported the synthesis of tetrahydroisoquinolines 13b and 4,5,6,7-tetrahydro-3H-imidazol[4,5-c]pyridines 14 via cyclocondensation of the appropriate dipeptidomimetic with various aldehydes (Fig. 6). 

The iron-mediated arylamine cyclization (mode A in Scheme 12) proceeds via the steps cyclodehydrogenation, aromatization, and concomitant demetalation, and can be achieved with various oxidizing agents (e.g., very active manganese dioxide [92, 93], iodine in pyridine [94—96], and ferroceifium hexafluorophosphate [92,97, 98]). Applications of this procedure to the total symthesis of carbazole alkaloids include for example hyellazole [97] and carazostatin [98] for reviews, see [18-20, 83]. More recent applications of this route to natural product synthesis are described in Sect. 3.1.1. 

Iodomethyl-substituted 1,4-dioxepan-2-ones (106) were obtained by iodolactonization of 3-oxa-6-heptenoic acids (104) with bis(5yw-collidine)iodine(I) hexafluorophosphate (105), as the transfer reagent. This reaction occurs regioselectively via an exo-mode cyclization <94JOC59i2>. 

The most important representative of cyclic iodonium salts, the dibenziodolium or diphenyleneiodonium (DPI) cation 238, known in the form of iodide, chloride, hydrosulfate, hexafluorophosphate, or tetrafluoroborate salts, can be obtained by three different procedures (A, B and C) summarized in Scheme 2.71. Method A, originally developed by Mascarelli and Benati in 1909 [355], uses 2,2 -diaminodiphenyl (235) as the starting material, which upon diazotization with sodium nitrite in a hydrochloric acid solution followed by potassium iodide addition, gives DPI 238 as iodide salt. A similar reaction starting from 2-amino-2 -iododiphenyl 236 affords DPI as hexafluorophosphate or tetrafluoroborate in excellent yields (Method B) [356]. The third method involves the peracetic oxidation of 2-iodobiphenyl (237) to an iodine(III) intermediate that then cyclizes in acidic solution (Method C) [357]. More recently, these methods were used to prepare the tritium labeled DPI and of its 4-nitro derivative [358]. 

Indole carboxylic acid 187 was converted via a Barton ester to fused indole 194 (11 examples, 5-79% yield). Barton ester 189 was formed by treatment of indole 187 with S-(l-oxido-2-pyridinyl)-l,l,3,3-tetramethyl thiouronium hexafluorophosphate (188, Garner s HOTT reagent) in the absence of light. Upon refluxing in MeCN, the Barton ester 189 decomposes to give nucleophilic ethyl radical 190, which adds to the unsubstituted carbon of alkyne 191 furnishing vinyl radical 192.This species cyclizes onto the C2 position of the indole to provide 193, which aromatizes to dehver the final product 194. The sequence proceeds without the need for an initiator or metal catalyst (14JOC5903). 

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