Silanes reaction with iminium salts

A second example is found in the photoaddition of allylic or benzylic silanes to iminium salts reported by Mariano and his co-woikers. - PET reactions of allylic or benzylic silanes with iminium salts generate two kinds of neutral radicals, allyl or benzyl radicals and a-amino radicals. The C-C bond-forming reaction between two different radicals occurs by cross coupling (Scheme 4). 

For example, allylic silanes react with photoexcited iminium salts by ET resulting in photoallylation. ° Key steps in such reactions are the cleavage of the C—Si... 

Mariano and coworkers have exploited this PET bond cleavage chemistry in intramolecular as well as intermolecular cyclization reactions [38]. The combined iminium-benzylsilane functionalities undergo intramolecular PET to provide an intramolecular amine radical/benzyl silane cation-radical pair by exciting either the iminium salt or the arene chromophore [38]. Cleavage of the benzyl C—Si bond presumably takes place with assistance of moderately weak n ldeophiles such as methanol. The diradical couples intramolecularly to provide an indolizidine derivative [38] in 90% yield. 

In a comparison study involving Mannich reactions of enol silanes, Holy et al. report that iminium salts (30H32) react at similar rates in DMF, where they are soluble, but in less polar solvents reduced solubility slows the rate and adversely affects the yield. For this reason the more soluble trifluoroace-tate (32) should be used in place of the iodide (30) or chloride (31) when conducting reactions in less polar solvents such as CH2CI2. Iminium salts (30)-(32) must be stored in the absence of moisture, while the iodide (30) should be kept from light. The trifluoroacetate (32) is a liquid and must be distilled to remove traces of TFA, which will adversely affect reactions with enol silanes and enolates. 

Two in situ methods for the generation of N,A/-dimethyl(methylene)iminium salts, which are limited to reactions with enol silanes, are also available and avoid the need to handle these moisture-sensitive reagents. In the first method, iodide (30) is prepared in situ by treating methyl(methylene)diamine (34) with chloroiodomeAane (equation DMSO must be used as... 

Reactions of enol silanes with (V,N-dimethyl(methylene)iminium salts occur under milder conditions than those of simple ketones because an initial enolization step is not required. The reaction is normally performed at room temperature, and aprotic solvents must be used to prevent hydrolysis of the enol silane. Danishefsky and coworkers, in their pioneering investigations of this reaction using TMS enol silanes and iminium iodide (30), have suggested the intermediacy of a silyloxonium salt (57), which loses a proton to give a 2-substituted enol silane (58) as its HI salt (Scheme 11). Subsequent hydrolysis of the enol silane during acid-base work-up affords the Mannich base (59). 

Table 9 Comparison of the Mannich Reactions of Enol Silanes with N.N-Dimethyl(methylene)iminium Salts...

Some comparisons between the yields of the Mannich reaction of enol silanes using in situ methods for preparation of the iminium salt and non in situ methods are shown in Table 9. Higher yields (20-30%) of P-amino ketones using in situ methods are seen in entries 2 and 4 but not in entry 1. Although a clear advantage of the in situ methods is not evident in these limited examples, in situ methods may be preferred from the standpoint of convenience. With aldehyde enol silanes (entry 3), the in situ method of Miyano et al is less practical due to elimination of the amino group, presumably caused by the strongly basic N,/V,/V, N -tetramethyl(methylene)diamine present in solution. 

As illustrated in Table 10, a wide variety of enolates undergo Mannich reactions with A A -dimethyl-(methylene)iminium salts. They include ester (entries 1), lactone (entries 2-4), a-ethoxycarbonyllactone (entry 5), acyliron (entry 6), aldehyde (entry 7), carboxylic acid (entry 8), and ketone (entries 9-12) enolates. Yields are gener ly comparable to the direct enol silane method except in the case of aldehydes... 

Imines, being neutral species, are less reactive than iminium salts. Consequently, active methylene compounds with pKn values greater than -15-16 must be preactivated as an enolate or enol silane derivative. Lewis acids are sometimes used in reactions with enolates to improve reactivity and stereoselectivity, but in contrast to the reactions of preformed iminium salts, Lewis acids are required in reactions with enol silanes. Additional activation of the active methylene compound or catalysis is not usually required in reactions with more acidic active methylene compounds (pATa values below -15-16). In these reactions, higher acidity not only gives higher enol concentrations but also serves to catalyze the reaction through protonation of the imine. 

Enolizable A -trimethylsilylaldimines can be generated in situ by the addition of organolithium reagents to bis(trimethylsilyl)formamide. These undergo addition reactions with enolates to form 3-lactams. Phosphonium salts used in catalytic amounts promote the reaction between aryl aldimines and silylketene acetals to form 3-amino esters. Mannich bases with N-2-hydroxyethyl-N-methyl substitution are prepared by the reaction of the iminium salt synthon, 3-methyl-1,3-oxazolidine, with enol silanes in the presence of chloromethylsilanes. ... 

Two in situ methods for the generation of A///-dimethyl(methylene)iminium salts, which are limited to reactions with enol silanes, are also available and avoid the need to handle these moisture-sensitive reagents. In the first method, iodide (30) is prepared in situ by treating methyl(methylene)diamine (34) with chloroiodomethane (equation 5) 36,37 DMSO must be used as solvent to achieve maximum yields. Cleavage of n-butyl dimethylaminomethyl ether (35) with TMS-I or TMS-OTf in MeCN comprises the second method (Scheme 5).38 A silyloxonium ion (36) was originally proposed as the reactive aminomethylating species, but a recent 13C NMR study of the reactions of ami-nol ethers with halosilanes in CD3CN-SO2 did detect the presence of iminium salts.39 Use of these methods in reactions with enol silanes is discussed in Section 4.1.2.2.2.iii. 

Larsen, S.D. Grieco, P.A. Fobare, W.F. (1986) Reactions of allyl silanes with simple iminium salts in water a facile route to piperidine via an aminomethano desilylation-cyclization process, J. Am. Chem. Soc., 108, 3512-13. 

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