Desilylative amination

Hydrosilylation of imine compounds was also an efficient method to prepare amines. The hydrosilylation product TV-silylamines can readily be desilylated upon methanol or water treatment, yielding the corresponding amines. The amines can be converted to their corresponding amides by subsequent acyl anhydride treatment. The first attempt to hydrogenate prochiral imines with Rh(I) chiral phosphine catalysts was made by Kagan102 and others. These catalysts exhibited low catalytic activity, and only moderate ee was obtained. 

Synthesis of a C(8)-C(18) segment of the larger fragment of lb using the same basic strategy is depicted in Scheme 25. Here, hydroxy ketone 176 was subjected to syn-selective (dr of crude product=90 10) reductive amination [42] with sodium cyanoborohydride and benzylamine followed by tetrahydro-oxazine formation using aqueous formaldehyde. The resulting heterocycle 182 was then converted to unsaturated ester 184 by successive desilylation, oxidation, and entirely (Z)-selective Horner-Wadsworth-Emmons olefination. Re-... 

Cycloheptanes.— The C-1—C-2 bond in -y-thujaplicin is essentially single, Co"-/3-thujaplicin-amine complexes have been described, and thermodynamic data on the U -/3-thujaplicin complex have been calculated. The biomimetic cyclization of the silyl enol ether (191) to karahanaenone (192), using methyl-aluminium bis(trifluoroacetate) is almost quantitative (192) is also synthesized by thermolysis followed by desilylation of the silyl enol ether (193) which is readily available from l-bromo-2-methyl-2-vinylcyclopropane and isobutyraldehyde. Dehalogenation of 3-bromo-l-iodo-3-methylbutan-2-one with Zn-Cu couple on alumina in the presence of isoprene yields (192) and minor amounts of the isomers (194) and (195) however, dehalogenation with Fc2(CO)9 favours (195). Acetolysis of karahanaenol tosylate yields anticipated p-menthane derivatives and no filifolene. ... 

A -Silylmethyl-amidines and -thioamides (42) (X=NR or S) undergo alkylation at X with, for example methyl triflate, and then fluorodesilylation to give the azomethine ylides 43 (identical with 38 for the thioamides) (25,26). Cycloaddition followed by elimination of an amine or thiol, respectively, again leads to formal nitrile ylide adducts. These species again showed the opposite regioselectivity in reaction with aldehydes to that of true nitrile ylides. The thioamides were generally thought to be better for use in synthesis than the amidines and this route leads to better yields and less substituent dependence than the water-induced desilylation discussed above. 

Acid fluorides can be used for a elean preparation of amides.9 96 The use of silylated amines is an elegant alternative, sinee liberated fluoride progressively desilylates them to more nucleophilic species. The reaction has to be started with a catalytic amount of fluoride (TBAF).92 Stannyl amines97 or phosphoryl amines (phosphoramides)98 have been used in similar reactions. 

Finally, the LDA deprotonation of amine N-oxides has been reported to generate azomethine ylides that can be trapped in [2 + 3] cycloadditions with simple alkenes.126 For example, N-methylpyrrolidine N-oxide (137) reacts with LDA in the presence of cyclopentene to give adduct (139 Scheme 31). A variety of other N-oxides behave similarly. Interestingly, there are no examples published to date where nonstabilized azomethine ylides generated by the desilylation procedure can be trapped by simple, unactivated alkenes. It is not clear whether these discrepancies are due to some fundamental difference in the reactive intermediate being generated, or whether the differences in environment are responsible for differing behavior. Further work is needed to establish this point. 

Trimethyl si lyl-Lo-acetonitrile has been shown to be highly versatile in the presence of cuprous chloride. Amines lead to formamidines through the insertion into their N-H bond whereas alcohols lead to desilylation products (see Section VLB).292... 

Conditions which serve to desilylate an /V-trimethylsilyl group or an ethynyltri-methylsilyl group do not result in the loss of a trimethylsilyl group a- to an amine.130,140 Another example is the hydrolysis of BSMA precursors with methanol in the presence of one equivalent of trimethylsilyl chloride (see Section III.B.2.h).186 189... 

Cleavage of the Si-C bond has gained tremendous importance in organic synthesis because of the diversity of the reactions in which organosilicon compounds can be engaged and the very mild conditions of these reactions.319 In some instances, total or partial desilylation is observed as a side or unexpected reaction. For instance, attempted cuprous ion-catalyzed insertion of trimethylsilylmethylisocyanide into the O-H bond of alcohols fails and desilylation occurs whereas insertion in the N-H bond of amines takes place in high yield (see Section IV.D.l.a).292... 

Fluoride ion-assisted desilylation has been extensively used to create an ylid from a /V-silyl methyl-quaternary ammonium salt. Its evolution to final produces) is variable and Sommelet-Hauser and Stevens rearrangement products were obtained (often as major products) in a ratio that can be shifted from one structure to another very close one, as in examples 1 and 2 dealing with //-benzyl salts.246,366 Differences in the solvents used are not significant because in the first example, HMPA does not reverse the ratio, yields and selectivity being just a bit lower, /so-toluene was proposed as an intermediate in example 1 it might also be the intermediate in example 2. Thus product partition reflects the relative ability of the C-H or the C-C bonds to be cleaved to produce aromatization with proton or a-amine carbocation migration. 

In the presence of two equivalents of silver fluoride, N-protected bis[(trimethylsi-lyl)methyl]amines lead also to azomethine ylids which can be trapped by dipolarophiles. The mechanism of the cycloaddition reaction involves sequential electron-Me3Si+-electron transfer process from the amine to silver fluoride, which forms silver metal, ruling out a fluoride-induced desilylation process. Although silver is recovered at the end of the reaction, a cheaper oxidizing reagent is still lacking.448,449... 

The key point is the deprotonation rather than the desilylation of the MSMA s cation radical, an unprecedented feature. Aimed at giving some support to this mechanism, the amine-flavine electron transfer photochemistry has been studied.493 Later, a polar mechanistic pathway was established in place of the SET mechanism mentioned above.494... 

Another approach involves the use of an electron-poor olefin acting both as an absorbing electron acceptor and as a radical trap. In this case, a PET reaction between a cyclohexenone derivative and a silylated amine led to a radical ion pair. Desilylation of the silyl amine radical cation intermediate in polar protic solvent (e.g., MeOH) and subsequent aminoalkyl radical attack onto the enone radical anion yielded the alkylated cyclohexanones [23]. 

An interesting application of PET-generated amine radical cations has been shown [87,99] to produce a-amino radicals by efficient desilylation of a-methyl silylamine 99. High yields of both pyrrolidines and piperidines (101) are... 

The efficient desilylation from amine radical cation in media favouring SSIP formation has also been used [104] for the sequential double desilylation reaction of amine 110 to generate azomethine ylide 111 which upon cycloaddition with a different dipolarophile gives a stereoselective pyrrolidine ring system 112 as depicted in Scheme 20. 

Photochemical Fe(CO)5-induced rearrangement of silylated allyl amine 9 gave N-silylated enamine 1015, which on subsequent Cu-catalyzed cyclopropanation by methyl diazoacetate afforded cyclopropane derivative 11. The use of an optically active catalyst gave an asymmetric induction of 56% ee for the cis isomer and 20% ee for the trans isomer. Further acid-induced ring cleavage afforded the -formyl ester 12, whereas reduction and desilylation produced aminocyclopropane carboxylic acid 13 (equation 2). 

Nucleophilic addition of secondary amines to 2,5-dialkylthiophene 1,1-dioxide is rather difficult. However, addition to 2,5-bis(trimethylsilyl)-, 2-trimethylsilyl-5-trimethylgermyl-, and 2,5-bis(trimethylgermyl)thiophene 1,1-dioxides (Scheme 33) occurs smoothly. Selective desilylation of 3-piperidino-2-trimethylsilyl-5-trimethylgermylthiophene... 

Destlylation. Anhydrous cesium fluoride desilylates trimethylsilylmethyl-sulfonium, trimethylsilylmethylammonium, and trimethylsilylmethylphosphonium salts at room temperature to produce ylides, which undergo various useful transformations. Use of potassium fluoride-18-crown-6 or a tetraalkylammonium fluoride gives products in low yield in these reactions. The trimethylsilylmethyl-onium salts are prepared by alkylation of sulfides, amines, imines, and phosphines with (trifluoromethanesulfonylmethyl)trimethylsilane (1). 

A synthesis of a series of 2-aminoindoles, an interesting and often synthetically challenging class of heterocycles, has been devised. Thus for example, the alkynylanilide 103 took part in a palladium-catalyzed process with the amine 104 to give the indole 105 after final desilylation <03AG(E)4257>. 

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