Allylsilanes with iminium ions

An example of a completely stereoselective cyclization of an allylsilane, leading to a seven-mem-bered ring in excellent yield, is known158. Treatment of the hydroxy compound with methanesulfonyl chloride and triethylamine in acetonitrile gives a single isomer of the bicyclic compound via cyclization of the (T )-iminium ion. 

Piperidines. Grieco et al. have described a general synthesis of piperidines by reaction of the acid salt of a primary amine with an allylsilane and 2 equiv. of formaldehyde in water. The reaction involves reaction of iminium ion (a), derived from the amine and formaldehyde, with the allylsilane to form a homoallylamine (b), which can form a second iminium ion (c), which cyclizes with capture of water to the piperidine. 

In the presence of the TiCLt catalyst, 6-amino-substituted allylsilanes readily react with isobutyraldehyde to yield piperidine derivatives 88 (equation 60)128. Presumably, an iminium ion intermediate is formed and the Boc group is replaced under the reaction conditions. It is noteworthy that the regioselectivity is different when acid chloride in used as the electrophile (cf Section II.B.5). 

Somfai et al. demonstrated that it is also possible to use A-sulphonyl groups (Somfai and Ahman 1992 Ahman and Somfai 1992 Weinreb 1997) using the same concept for the cyclization step developed by Speckamp with the allylsilanes (Esch et al. 1987). In this case, the starting product was the L-pyroglutamic acid, inside the succinimide (Esch et al. 1987), allowing the enantioselective synthesis of the (+)-anatoxin-a. The key step consisted of an intramolecular cyclization of an 7V-tosyl iminium ion, catalysed by a Lewis acid, TiCl, to set up the desired bicyclic ring system (Somfai and Ahman 1992). 

In addition to their use in Mannich (and variant) reactions, iminium ions are useful for other cationic type cyclizations. Corey employed a novel tandem iminium ion cyclization as part of an elegant cascade used for the synthesis of aspidophytine. The reaction of tryptamine 292 and dialdehyde 293 in CH3CN at ambient temperature afforded the pentacyclic skeleton of the alkaloid (296 Scheme 54) (99JA6771). Condensation of the free amino functionality of 292 with the dialdehyde produced a dihydropyridinium intermediate 294 that then cyclized onto the indole n-bond to give 295. The iminium ion so produced underwent a second cyclization with the tethered allylsilane moiety to give 296. Protonation of the enamine in 296 provided still another iminium ion (297) that was then reduced with NaCNBH3 to furnish 298 in 66% yield. All of the above reactions could be made to occur in a single pot. 

The synthesis of ( )-yohimbone by Grieco and Fobare illustrates the use of an allylsilane to terminate an iminium ion initiated polyene cyclization. The o/E-ring system of the target alkaloid was assembled by treating diene amines (114) with formaldehyde and CF3CO2H in aqueous THF to give (115) in good yield. Only the rrans-hydroisoquinoline stereoisomer was produced (Scheme 42). 

A variety of tetrahydropyridines have been prepared with complete regiocontrol by the reaction of 4-(trimethylsilyl)-3-butenylamines with aldehydes and acid (Scheme 43). This reaction, although ostensibly an iminium ion-vinylsilane cyclization, is believed to occur by the pathway illustrated in equation (11), in which ring formation ensues from the allylsilane sigmatropic isomer. Consistent with this mechanism pathway, either the ( )- or (Z)-vinylsilane amine stereoisomer can be employed. 

The occurrence of a fast cationic aza-Cope reairangement has been proven in the case of vinylsilane cyclizations (equation 109). Enantiomerically pure ethoxycarbamate (148) cyclizes under the influence of BF3-Et20 to a I I mixture of racemic tetrahydropyridines (149) and (150). Thus, the equilibration of iminium ions (151) and (152), attended with racemization (equation 110), occurs much faster than ir-cy-clization. Because allylsilanes are more nucleophilic than vinylsilanes, ir-cyclization probably takes place from (152). The fast rate of cyclization of allylsilanes is apparent from the cyclization via (140), where cationic aza-Cope rearrangement cannot compete (equation 105). 

It seemed interesting to trap the iminium ion intermediate by performing an intramolecular aSH, so we plarmed a CHC/aSH/hydroformylation domino reaction (Scheme 10). This reaction involves an allylsilane present on the amine moiety which, in an acidic medium, reacts with an acyliminium ion derived from the CHC to form a vinyl group. The resulting vinyl double bond must be hydroformylated regioselectively by the rhodium complex present in the reaction medium to lead to a functionalized polycyclic structure. 

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