Iminium salts cyclization

Addition Reactions.—As the years go by, the importance of electron transfer processes is becoming increasingly apparent, and hardly a month passes without the reinterpretation of a reaction as involving such a process. This has stimulated the publication of review articles such as that by Mattes and Farid on the electron transfer reactions of alkenes, and the more specific reviews by Mariano on the application of electron transfer photochemistry to iminium salts. In this area Mariano and his co-workers have reported further on the electron-transfer-initiated photochemistry of iminium salts (1), and in detail on the spiro-cyclization methodology of iminium salt cyclization. ... 

The decisive aspect in this plan is to direct the regioselectivity of an iminium salt cyclization. 

The action of ammonia on N-(5-aryl-l,3-oxathioI-2-ylidene) tertiary iminium salts (7) affords linear intermediates that cyclize to 2-amino-4-phenylthiazoles (Scheme 7) (45). 

TL2733,82TL2737). The reaction proceeds through an aza-Cope rearrangement of the initially formed iminium salt, followed by intramolecular cyclization. 

The iminium salt 165, derived from acid treatment of 1,4-dihydropyridine 164, on intramolecular cyclization on the indole nucleus gave pentacyclic compound 166 (83T3673). The tmns stereochemistry of H3 and H9 in 166 (biogenetic... 

The Bischler-Napieralski reaction is one of the traditional methods for isoquinoline synthesis, and has been applied to the preparation of fused quinolizidine systems. One simple example is the transformation of compound 246 into a 9 1 mixture of diastereomers 247 and 248 by treatment with phosphorus oxychloride followed by sodium borohydride reduction of a nonisolated iminium salt resulting from the cyclization (Scheme 49) <2000BMC2113>. 

The excellent reducing properties of potassium tetracarbonylhydrido-ferrate have been used to good effect in providing an efficient general piperidine synthesis from alkyl and aryl amines and glutaraldehyde210 (Scheme 138). The reaction probably proceeds via reduction of intermediate Schiff bases and cyclization via the iminium salt. 

After its isolation, the structure of alkaloid deplancheine (7) was unambiguously proved by several total syntheses. In one of the first approaches (14), 1,4-dihydropyridine derivative 161, obtained by sodium dithionite reduction of A-[2-(indol-3-yl)ethyl]pyridinium salt 160, was cyclized in acidic medium to yield quinolizidine derivative 162. Upon refluxing 162 with hydrochloric acid, hydrolysis and decarboxylation took place. In the final step of the synthesis, the conjugated iminium salt 163 was selectively reduced to racemic deplancheine. 

Another interesting example of a photochemi-cally induced domino process is the combination of the photocyclization of aryl vinyl sulfides with an intramolecular addition as described by Dittami et al. [901 as intermediate a thiocarbonyl ylide can be assumed. The domino-Norrish I-Knoevenagel-allyl-silane cyclization developed by us allows the efficient stereoselective formation of 1,2-trans-subsituted five- and six-membered carbocycles.1911 A photochemical cycloaddition of enamino-aldehydes and enamino-ketones with the intermediate formation of an iminium salt followed by addition to allylsilanes gives access to novel bicyclic heterocy-des. New examples of photochemically induced... 

Two new syntheses to fused isoxazoles are worth mentioning. In a study for the synthesis of various related fused [l,3,5]triazinium salts, Okide described <1994JHC535> the conversion of 3-amino-5-methylisoxazole 223 with the iminium salt 224. The quaternary perchlorate salt 225 was obtained in medium yield (44%). A Russian research group <2004KGS592> reported that the isoxazole derivative 226 undergoes thermal cyclization when heated in xylene at higher temperature for an extended time, and the cyclized product 227 can be obtained in 53% yield. 

Total synthesis of the representative protoberberines, (+)-xylopinine 151 (equation 71) and (+)-stylopine 152 (equation 72), have been achieved using silylarene-iminium salt photochemistry128. The photochemical routes appear to be superior to alternative ground-state methods involving dipolar cyclizations. 

Synthesis of antx-a has been done through a ring expansion of cocaine (20), from 1, 5-cyclooctadiene (21) and by intramolecular cyclization between an iminium salt and a nucleophilic carbon atom (22). The structure of antx-a is given in Fig. 1. 

An example of the 7d-type cyclization is that of iminium salt 38b obtained by decarbonylation of a-(ferf-amino) acid 38a. Attack of the nucleophilic malonate on the newly formed electrophilic carbon of the iminium ion gives dicarboxylate 39a (79JOC4173). 

Spiro-isoxazoline 57 (Scheme 16) undergoes thermolytic rearrangement followed immediately by cyclization of the intermediate enaminone to bicyclic 58 (89J(P1)1253). Imine 59 when heated gives iminium salt 60, hence providing a new and efficient route to parent substance 2 (03T3099). 

The synthesis of iminium salt 85 by soda-lime pyrolysis through an intermediate enamine (83CJC2016) is inferior to that of salt 60 (Scheme 16). Cathodic cyclization of l-(E-oxoalkyl)pyridinium salts gives dia-stereomeric hydroxy compounds 86 and 87 in yields of 14-16% each (95AGE2007). 

Intramolecular Mannich type reaction of the conjugated iminium salt 426 should lead to ellipticine (228) via an intermediate 427. Alternatively, the conjugated iminium salt 426 could hydrolyze to afford the 2-vinylsubstituted indole 428, which, on cyclization through an intermediate 429, would lead to guatambuine (233). This alkaloid, on demethylation and dehydrogenation, should afford olivacine (238a) (375) (Scheme 3.11). 

When the zwitterionic 1,3-oxazine iminium salt 113, which is a 1 1 mixture of ( )- and (Z)-isomers A and B, was treated with phenylhydrazine, pyrazolo[3,4-, [l,3]oxazine derivatives 114 were formed in moderate yields (Equation 7). Surprisingly, the products of the cyclizations 114 existed only as the ( )-isomers. Products with an ( )-double-bond were also formed exclusively on nucleophilic replacement of the 4-chloro substituents of 113A and 113B by various amines or a-amino esters <1999H(51)2893>. 

Hydrolytic conditions are tolerated by dihydrobenzoxazines, and this allows the selective hydrolysis of the ester group of 243 into the free acid with 10% sodium hydroxide <1983JHC45>. The nitrile of 244 was converted into the iminium salt followed by hydrolysis to give the ester 70 <1987M273>. Conversion of 245 into an iminium salt followed by base treatment to give the a-ethoxy enamine then allows cyclization with an aldehyde to give product 246 as shown in Scheme 27 <1986H(24)3483>. 

The notion that silyl groups and alkyl groups belong to different categories in the polarity sense is now established. The cyclization of an iminium salt by alkyne participation is dramatically controlled by the terminal substituent of the acetylene in... 

The cyclization reaction developed by Scheffold, and shown in Scheme 65, makes use of the addition of an amidine to an iminium salt, and produces a product of reduced porphinoid character.196 197... 

The Pictet-Spengler cyclization of iminium salts, generated in situ from 3-indolyl)ethyl substituted amino acid esters 257 and various aldehydes, has been found to proceed with high stereoselectivity (up to 98.5 1.5)392. 

One application of lactone 140 as a chiral synthon may be found in the asymmetric synthesis of (+)-12b-epidevinylantirhine (143), a cleaved product of geissoschizol (Scheme 28) [62-63]. Treatment of 140 with tryptamine in hot toluene afforded 142, which cyclized to lactam 142 by mesylation and an Sn2 displacement. Hie Bischler-Napieralski reaction of 142, followed by reduction of the resulting iminium salt with NaBH4, produced stereoselectively, the indolo[2,3-a]quinolizine as a single isomer, which was further reduced with DIBAL to give (+)-12b-epidevinylantirhine (143). 

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