Aminomethylation Aminomethyl silanes

Keywords lithiumorganyle, (aminomethyl)silane, (lithiomethyl)silane, stereogenic center... 

Summary Our research on a-metalated organosilanes currently focuses on (aminomethyl)silanes containii a defined stereogenic center next to the silicon center. A synthetic route based on the preparation of 2-silyl-substituted pyrrolidines was developed. The racemic product could be synthesized by metalation of JV-Boc-pyrrolidine in the presence of TMEDA and conversion with the corresponding chlorosilane, whereas the enantioenriched form was achieved by metalation in the presence of the chiral amine (-)-sparteine. Subsequent metalation and transformation reactions yielded the formation of the corresponding (aminomethyl)(lithiomethyl)silane. 

According to the the work of P. Beak and coworkers on 2-substituted pyrrolidines [2], the following synthetic route, containing asymmetric deprotonation and transformation of the protecting group, was chosen for the preparation of the (aminomethyl)silanes 3 and 5. The (aminomethyl)(lithiomethyl)silane 4, a molecule of type E (Scheme 1), was achieved by subsequent metalation of 3 (Scheme 2). 

Scheme 2. Preparation of the (aminomethyl)silanes 3 and S and of (aminomethylXlitliioinetbyi)silaAe 4.

As a result of the numerous possibilities for modification at both the nitrogen and the silicon centers, this class of (aminomethyl)silanes has considerable potential for use in synthesis of pharmaceutically interesting compounds [11]. The metalated species can be used as reagents for the transfer of stereogenic centers [la] as well as building blocks for novel ligands of organometallic systems [12]. 

New Organosilicon Reagents Synthesis, Structure, and Reactivity of (Lithiomethyl)(aminomethyl)silanes... 

Summary (Aminomethyl)silanes have been prepared by new synthetic routes starting from lithiosilanes or (lithiomethyl)amines. (Lithiomethyl)(aminomethyl)silanes were formed by metallation with lithioalkyls. A sulfur-substituted (lithiomethyl)(aminomethyl)silane and a THF adduct are characterized by single crystal X-ray diffraction. In reactions of (lithiomethyl)(aminomethyl)silanes with aldehydes or ketones no clear addition/depro-tonation profile was observed. 

Unaware of the above mentioned work we explored, almost at the same time, the similar theme and encountered some very interesting and novel findings about the synthesis and structure of (lithiomethyl)(aminomethyl)silanes. We are presenting new synthetic routes to (aminomethyl)silanes and (lithiomethyl)(aminomethyl)silanes and we want to give experimental information on two questions concerning (lithiomethyl)silanes (i) aggregation of (lithiomethyl)(aminomethyl)silanes in the solid state (ii) stabilizing effects of silicon in (lithiomethyl)silanes. 

We have prepared (aminomethyl)silanes (F) by the known reaction (i) and three new (ii-iv) synthetic routes (Scheme 1) ... 

Aminomethyl)silanes (E) can be metallated by lithiumalkyls and characterized by trapping with disulfides (Scheme 3). The (phenylthiomethyl)(aminomethyl)silanes G can be metallated again in toluene or THF In reactions of (lithiomethyl)(aminomethyl)diphenylsilanes with aldehydes or ketones we observed no clear addition/deprotonation profile. The (lithiomethyl)silanes H add to ketones with de up... 

Further related work on the synthesis, structure, and reactivity of (lithiomethyl)(aminomethyl)silanes is currently under way to understand more about the behavior of these systems in solution and in the solid state. 

The aziridine ring may also be opened in an electrophilic fashion. For example, the aziridine nucleus of the functionalized allyl silane 113 undergoes intramolecular ring opening in the presence of boron trifluoride etherate to give the aminomethyl vinyl cyclohexane 114 in 90% yield as a 2.7 1 mixture of cis and tram isomers [95TL3793]. 

C10H21NO4SI triethoxy(3-isocyanatopropyl)silane 24801-88-5 556.15 49.304 1,2 21217 C10H22N2O 1 -amino-3-aminomethyl-3,5,5-trimethyl cycloh 25724-35-0 389.15 33.344 2... 

As part of our studies on a-metalated organosilanes, we use (aminomethyl)(lithiomethyl)silanes of the general type A [1]. Systems of types B and C containing defined stereochemical information could be synthesized starting from either chiral amines or from 5i-chiral silanes. A new structural motif (D) arises if the stereogenic center is adjacent to silicon (preferably as part of a rigid system). The goal of these studies was the synthesis of the enantiomerically pure, lithiated 2-silyl-substituted pyrrolidine E. 

The metalation of the 2-silyI-substituted pyrrolidine 3 with t-BuLi resulted in the formation of the corresponding (aminomethyl)(lithiomethyl)silane 4, which represents a new structural motif for (aminomethyl)(lithiomethyl)silanes. 

Our ongoing research on (aminomethyl)(lithiomethyl)silanes focuses on modification of the substituents at the nitrogen center. The unprotected 2-silyl-substituted pyrrolidine 5 is a very useful starting point for the synthesis of different A -substituted pyrrolidines like rac-6. The racemic compound rac-S and the enantioenriched compound (iS)-5 could be s)mthesized by reaction of the Af-Boc-protected compound rac-2 or (S)-2 trifluoroacetic acid (TFA) [10]. In subsequent reactions it was possible to introduce a methyl group at the nitrogen center by conversion of rac-S with methyl... 

Table 8 highlights some versatile applications of the Mannich reaction of enol silanes, providing Mannich bases that in some cases are very difficult, if not impossible, to obtain using the classical method. Regiocontrol is observed in the preparation of the two Mannich bases of 2-methylcyclohexanone from the corresponding regioisomeric enol silane derivatives (entries 1 and 2)P Aminomethylation of the enol... 

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. 

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