Silylated nucleophiles, ring

Lastly, Antilla has disclosed a novel asymmetric desymmetrization of a wide range of aliphatic, aromatic, and heterocyclic meso-aziridines with TMS-N3 promoted by 11 and related 12 (Scheme 5.31) [56]. Uniquely, this is one of only several reports of electrophilic activation of nonimine substrates by a chiral phosphoric acid. Mechanistic studies suggest that silylation of 11 or 12 by displacement of azide generates the active catalytic species A. Consequently, the aziridine is activated through coordination of it carbonyl with chiral silane A to produce intermediate B. Nucleophilic ring opening by azide furnishes the desymmetrized product and regenerates 11 or 12. 

An IV-heterocyclic carbene (similar to that in Scheme 15) has proved to be an effective catalyst for the nucleophilic ring opening of IV-tosylaziridines by silylated nucleophiles (MesSiX, X = N3, Cl, I).45 Yields range from 89 to 99% for reaction at the least substituted carbon, except when a phenyl group on one of the carbons of the aziridine ring induces predominant attack at the benzyl carbon. The stereochemistry is consistent with the SN2 mechanism and THF was found to be the best solvent for the reaction. 

The ring opening reaction of A-tosylaziridines with certain silylated nucleophiles via a similar activation has been reported recently (Wu et al. 2006). 

The Paquette team proceeded ahead in the expectation that aldehyde 31 would outperform other chiral C10-C17 subunits (Paquette, Pissarnitski, and Barriault 1998). Their routing began with oxirane 22, which is readily available from (i )-(-)-pantolactone (Scheme 15.2). After 0-silylation, 23 was reacted with dilithioacetate in dimethoxyethane to induce nucleophilic ring cleavage with follow-up cyclization. The resulting lactone 24 could be successfully monomethylated under closely... 

The y-lactam 110 is prepared by the reaction of the lithium silyl-substituted ynolate 105 with the aziridine 108 activated by a p-toluenesulfonyl group. The initial product is the enolate 109, which can be acidified to yield the a-silyl-y-lactam 110. Intermediate 109 can be trapped by aldehydes to afford the a-alkylidene-y-lactams 111 via a Peterson reaction (equation 45) . These reactions may be considered to be formal [3 + 2] cycloadditions as well as tandem reactions involving nucleophilic ring opening and cyclization. 

A further application of chiral 1,3-dioxanes of type 21 is the stereoselective fission of the 1,3-dioxane ring, e.g. of 25, by silyl nucleophiles in the presence of TiCl4 or other titanium compounds ... 

Regiospecific nucleophilic ring opening of oxetanes to 3-silyl-oxyisocyanides with trimethylsilyl cyanide/Znl2 in dichloromethane has been reported, and this has led to the synthesis of amino-alcohols by hydrolysis of the isocyanide group. ... 

Ph3Si ethylene oxide catalytically adds PhSH to give a- and -adducts in 6 1 ratio, and serves as a vinyl dication equivalent with RCu to give alkenes stereoselectively, while epoxides rearrange in the presence of silylated nucleophiles Diphenylmethylsilylation of cyclopropane carboxylates gives the C-silylated ester which then form C-silylated cyclopropyl ketones, P-silyl cyclopropyl carbinols, and alkylidene cyclopropancs, which ring expand to the... 

Treatment of an oxirane bearing no silyl group with a silyl nucleophile leads to the same result. Both trimethylsilylpotassium and dimethylphenylsilyllithium effect smooth conversion of oxiranes into alkenes with inversion of configuration, nucleophilic ring opening being followed by spontaneous syn-y6-elimination (Scheme 2.121) [341, 342]. 

Silyl ethers serve as preeursors of nucleophiles and liberate a nucleophilic alkoxide by desilylation with a chloride anion generated from CCI4 under the reaction conditions described before[124]. Rapid intramolecular stereoselective reaction of an alcohol with a vinyloxirane has been observed in dichloro-methane when an alkoxide is generated by desilylation of the silyl ether 340 with TBAF. The cis- and tru/u-pyranopyran systems 341 and 342 can be prepared selectively from the trans- and c/.y-epoxides 340, respectively. The reaction is applicable to the preparation of 1,2-diol systems[209]. The method is useful for the enantioselective synthesis of the AB ring fragment of gambier-toxin[210]. Similarly, tributyltin alkoxides as nucleophiles are used for the preparation of allyl alkyl ethers[211]. 

The formation of the (SiN)2 ring can be explained by a nucleophilic 1,3-rearrangement of a methanide ion at silicon. The cyclic ylide is formed because the two nitrogen atoms are identically substituted and a silyl group migration would be without energy profit in such a molecule. 

The domino reaction is initiated by the chemoselective attack of the carbanion 2-458 on the terminal ring carbon atom of epoxyhomoallyl tosylate 2-459 to give the alkoxides 2-460 after a 1,4-carbon-oxygen shift of the silyl group. The final step to give the cyclopentane derivates 2-461 is a nucleophilic substitution. In some cases, using the TBS group and primary tosylates, oxetanes are formed as byproducts. 

Addition of alkyllithium to cyclobutanones and transmetallation with VO(OEt)Cl2 is considered to give a similar alkoxide intermediates, which are converted to either the y-chloroketones 239 or the olefinic ketone 240 depending on the substituent of cyclobutanones. Deprotonation of the cationic species, formed by further oxidation of the radical intermediate, leads to 240. The oxovanadium compound also induces tandem nucleophilic addition of silyl enol ethers and oxidative ring-opening transformation to produce 6-chloro-l,3-diketones and 2-tetrahydrofurylidene ketones. (Scheme 95)... 

Reactions with dialdehydes allow the introduction of two additional rings in one step. Thus, condensation of 1 -(2-aminoethyl)pyrrole with glutaraldehyde and benzotriazole gives tricyclic intermediate 627 in which the benzotriazolyl moiety can be readily substituted with nucleophiles to give products 628 (Scheme 97) <2002JOC8220>. Condensation of ethyl ester of L-tryptophan with 2,5-dimethoxytetrahydrofuran and benzotriazole in acetic acid gives tetracyclic intermediate 629 which upon treatment with nucleophiles (silyl derivatives) is converted to products 630 <1999T3489>. 

It is very likely, that this reaction occurs due to the equilibrium between trimethylsilyl halide and a nitrogen-containing nucleophile, which increases the electrophilicity of silyl Lewis acids. It should be noted that the configuration of stereocenters at the carbon atoms of the oxazine ring is partially distorted. Hence, it is assumed that the reaction proceeds through the intermediate cation B, which is partially isomerized into the stereoisomeric cation B through the open chain cation B". 

---