Destannylation Reactions

The stereospecific preparation of E- and Z-a-fluorovinylstannanes via the radical reaction of the corresponding a-fluorovinylsulfones with tributyltin hydride has been reported by McCarthy et al. These reagents undergo a variety of destannylation reactions including protolysis, deuterolysis, acylation, iodina-tion, electrophilic fluorination and the Stille coupling reaction [186-189] (Scheme 66). The last reaction has been employed successfully in the synthesis of a fluorinated thymidylate synthetase inhibitor [189] (Scheme 67). 

The Stille reaction of fluorovinyltin reagents offers the greatest synthetic flexibility, and reactions with alkanoyl (e.g., formation of 5 ), aryl (e.g., formation of 6 ), allyl and vinyl halides have been reported. Stereospecific destannylation reactions ofa-fluorovinyltin reagents include protonolysis, deuterolysis and iodination reactions. Electrophilic fluorination of the C —Sn bond has also been reported. 

Destannylative reactions. l-Trimethylstannyl-2,4-pentadiene reacts with aldehydes and ketones in a -y-selective manner, whereas conjugated dienes are generated from 3-(tributylstannyl)propenyl pyrans. ... 

TABLE XXIII. Ethynyl- and Polyethynylpyrazoles Prepared by Desilylation, Destannylation, and Decarboxylation Reactions [71ZOB2230 73S47 75KGS1678 88M253 96BMCL1279 96MCR293]. 

Secondly, destannylation appears to be more sterically hindered than the hydrogen exchange reaction, since in the latter the a-position of naphthalene is rate-... 

The synthesis of different substituted finans by cyclization of 4-pentynones using potassium tert-butoxide in DMF was reported <96TL3387>. Dihydrofuran 32 can be prepared by a destannylative acylation of l-[(2-methoxyethoxy)methoxy]-2-(phenylsulfonyl)-2-(tributylstannyl)-cyclopropane. Treatment of 32 with BFj-EtjO yields 3-acyUurans via an intramolecular Prins-type reaction of the resulting oxonium ion intermediate <96TL4585>. 

Entries 20 to 23 involve additions to C=N double bonds in oxime ethers and hydrazones. These reactions result in installation of a nitrogen substituent on the newly formed rings. Entry 20 involves the addition of the triphenylstannyl radical to the terminal alkyne followed by cyclization of the resulting vinyl radical. The product can be proto-destannylated in good yield. The ring closure generates an anti relationship for the amino substituent, which is consistent with the TS shown below. 

Aromatic fluorination can be carried out by a regiospecific destannylation process shown in reaction 69. This is an effective method for producing fluorinated m-tyrosine and other radiopharmaceuticals, as shown in reaction 70. The process can be applied for radiolabelling with 18F, denoted as F in these reactions, and the products used as radioactive tracers for clinical and fundamental investigations318-321. 

The Stille coupling was also employed successfully to prepare covalently bound DNA base-pairs. 1,4-, and l,3-bis(stannyl)benzenes were used to connect purine units covalently through a phenylene linker. The reactions gave the desired products in mediocre yield, along the by-products of destannylation and mono-coupling (8.21.), The extension of the procedure to benzene-1,4-diboronic acid met with limited success.29... 

Reactions of 2-stannyl-3-silylpropene with acid chlorides in the presence of Lewis acid afford vinylsilanes 92 via 1,2-silyl migration followed by destannylation (equation 70)138. 

Desilylation, degermylation, destannylation, and deplumbylation have also been examined in detail. The relevance of these reactions to the present discussion depends on the similarity of the mechanism for... 

Norman and Radda (1962) apparently do not consider that p and r are independent parameters for the substitution reactions. They argue, largely on the basis of the results for destannylation, degermylation, and desilylation, that p and r are related. 

The photoreactions of iV-(trimethylsilyl)methyl- or iV-(tributylstannyl)methyl-substituted a-ketoamides resulted into the formation of complex mixtures including azetidin-2-ones and oxazolidinones with or without the trimethylsilyl or tributylstannyl moiety <2004JOC1215>. It was observed that the reaction of A-(trimethylsilyl)methyl-substituted a-ketoamides proceeded by competitive hydrogen abstraction and sequential single electron transfer (SET)-desilyla-tion pathways, whereas the reaction of iV-(tributylstannyl)methyl-substituted a-ketoamides preferred the sequential SET-destannylation pathway. 

All the examples described above involved the reaction of diazoacetate derivatives with silver salts to initiate the formation of a putative silver carbene however, other pathways exist. For example, Porcel and Echavarren have reported an intramolecular cyclization of an allylstannane to a pendent alkyne (Scheme 8.22) that involves the intermediacy of a silver carbene.52 As can be seen in Table 8.12, the reactions proceeded in moderate to excellent yield, providing the dienylstannane, while in some cases, reductive destannylation occurred. Several asymmetric reactions were reported with substrate ( )-145d, leading to the formation of the expected adduct in reasonable enantioselectivities (ee = 73-78%) in a preliminary screen with a number of different ligands. 

Retention in the reactions of 15 is established both from presumed retention in the Sn-Li exchange step of a stannylation-destannylation sequence and by evidence that the s-BuLi-(-)-sparteine complex used to make the organolithium reliably removes the pro-/ proton adjacent to a carbamate (see below for crystallographic evidence involving a similar compound).11 The stereochemistry of the products 16, almost all formed essentially in enantiomerically pure form, was proved for the C02 adduct and the Mel adduct by comparison with known compounds. The only electrophiles for which incomplete retention of stereochemistry has been observed are the benzylic or allylic halides. These probably react in part by single electron transfer SE1 mechanisms, rather than by partial SE2inv.15 For example, 15 reacts with allyl bromide to give 16 (E = allyl) with only 42% ee. 

Base-catalyzed desilylation of thiophenes has been used to examine both the mechanism of the reaction, and the effects of substituents [76JCS(P2)925 81JOM(204)153]. In this work the reactivities of the 2-positions of furan, benzo[f>]furan, and benzo[ ]thiophene were also examined, as were base-catalyzed degermylation (cleavage of GeR3) and destannylation (cleavage of SnR3). 

Insertion reactions using CO and CH2N,2. Radical cyclization reactions of azaenynes in the presence of butyl stannanes in carbonylation conditions furnished /3-lactams <2003JA5632>. Azocanone 150 (Scheme 62) was prepared in good yield from enyne 149. The reaction occurred via a-stannylmethylene lactam of type 154 (Scheme 63). This free radical-mediated stannyl carbonylation is quite versatile and provides a general [ -pl]-type annulation leading to 4-exo and 8-exo systems. The yield of the isolated stannylene lactam intermediate 154 was reported as 61%, while the destannylation to lactam 150 was quantitative. 

Base-catalysed hydrolysis using alkali metal hydroxides or carbonates in aqueous methanol or THF remains the commonest method for cleaving simple esters limited mainly by the stability of the substrate to the basic conditions. In more complex substrates, lithium hydroxide in a mixture of THF-methanol-P O (2 2 1) is the base of choice.1-3 In a synthesis of Lepicidin A, Evans and Black4 accomplished the hydrolysis of a methyl ester with lithium hydroxide in aqueous /err-butyl alcohol at 35 °C [Scheme 6.1). Destannylation that accompanied hydrolysis with other solvents was not observed nor was harm inflicted on the TIPS and TES ethers. In a synthesis of cydoisodityrosine derivatives, Boger and co-workers attempted to hydrolyse methyl ester 2 1 [Scheme 6.2] with 1-3 equivalents of lithium hydroxide in a mixture of THF-methanol-HaO (3 1 1) at room temperature, but the desired hydrolysis was accompanied by scission of the tripeptide side chain from the ring system. However, when the reaction was conducted in the presence of the more nucleophilic lithium hydroperoxide, the desired hydrolysis was achieved in 97% yield without racemisation. 

An impressive procedure for 2-stannylindole is depicted in Scheme 53 [219]. Since the product is prone to proto-destannylation, in situ generated indolyltin reagent is directly used for the cross-coupling reaction. Thus the overall schemes provides a direct synthesis of 2,3-disubstituted indoles from 2-alkenylphenyl-isonitrile [51,220,221]. 

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