Vinyl stannane synthesis

The Stille reaction has been successfully applied to a number of macrocyclic ring closures.207 In a synthesis of amphidinolide A, the two major fragments were coupled via a selective Stille reaction, presumably governed by steric factors. After deprotection the ring was closed by coupling the second vinyl stannane group with an allylic acetate.208... 

The following two schemes exemplify the synthesis of piperidines via 1,4-addition of amines. In the first scheme below, a one-pot Stille coupling/double Michael addition, starting from readily available vinyl stannanes, is used to generate piperidinones 174 <06SL547>. An example of the reduction of piperidinone 174 to piperidine 175 is also highlighted. 

In the more prolific aspect of the Stille couplings involving a pyrimidine fragment, pyrimidinyl halides or triflates have been coupled with a variety of stannanes. When there is only one reactive halide on the pyrimidine ring, the reaction outcome is straightforward with no regiochemical concern. The simpler stannanes are vinyl stannanes [35-37]. More complicated variants include stannylquinones [38] and l-(trialkylsilyloxy)vinyltin [39] as illustrated by the synthesis of 66. 

Stannyl cuprates couple with vinyl halides or triflates [16c-d, 85], and a vinyl stannane produced this way has been used in the synthesis of 7-[( )-alkylidene]-cephalosporins [117]. Vinyl substitution reactions starting from dihydrofurans are... 

Details of the Janda-Chen synthesis were as follows. A tetrahydropyran (THP) linker was attached to the NCPS support enabling attachment of alcohols via THP ether formation.13 The THP-NCPS resin 1 is derivatized with / -(+)-4-hydroxy-2-cyclopentanone 2, giving the THP ether-based resin 3, followed by coupling of the C13 20 fragment by enone-cuprate addition. The cuprate required was generated from the corresponding E-vinyl stannane 4. The resulting enolate was trapped as the silyl end ether... 

Palladium-mediated addition of silyl stannane reagents to alkynyl ethers has been employed for the synthesis of aliphatic acyl silanes in very good yields via the intermediate a-alkoxy-/J-stannyl vinyl silanes (enol ethers of acyl silanes)82. In a second palladium-catalysed step, the vinyl stannane moiety could be coupled to suitable halides before hydrolysis to the acyl silanes with trifluoroacetic acid (Scheme 11). 

The synthesis of A-fused tricyclic (3-lactams involving a radical cascade sequence in enyne 2-azetidinones 114 and 115 bearing a methylenecyclopropane unit has been reported [82]. Slow addition of Bu3SnH/AIBN to a refluxing solution of 114 gave tricyclic vinylstannane 116 as a single stereoisomer in 42% yield, whereas cyclization of 115 under identical conditions gave fused heterocycles 117 and 118 in 73 and 11% yield, respectively, in all three cases via a 7-endo cyclization. Treatment of vinyl stannanes 117 and 118 with PPTS in dichloromethane yielded a common tricyclic product 119 (Scheme 40). 

The balanced reaction for a synthesis of an intermediate (13.57) for a fluvastatin analogue is shown here. This reaction relies on a vinyl stannane (13.a). Stannanes are toxic and generate large amounts of waste. Calculate the atom economy for this reaction. 

The Stille reaction, which represents over half of all current cross-coupling reactioi has been used in total synthesis with excellent results. The reaction may also be carried o intramolecularly and with alkynyl stannanes instead of the more usual aryl or vinyl stannan even to form medium-sized rings. This example forms a ten-membered ring containing t alkynes. 

The synthesis of electron-deficient diene 285 was achieved by the Stille coupling of P-trifluoromethanesulfonyl-a,P-unsaturated sulfone (284) with a 3-stannyl-a,P-unsaturated ester (283) (Scheme 74).148 Similarly, the preparation of a diverse range of enantiomerically pure 1- and 2-sulfinyl dienes has been achieved via Stille coupling of halovinyl sulfoxides and vinyl stannanes.149,150 Enantiomerically pure 1- and 2-sulfinyl dienes have been used extensively in asymmetric Diels-Alder reactions.111... 

As shown in Scheme 11.72, direct lithiation of protected glucal 346 using tBuLi to form 347 has been proposed [258]. From the lithium anion 347 it was also possible to prepare the vinyl stannane 348, which can be isolated and retreated with nBuLi to give the lithio derivative 347 [259,260]. This anion has been condensed with aldehydes and esters. Lithiation of 2-phenyl-thioglycal was also effective [261]. A good example of the use of such a dihydropyran anion could be found in a pederin synthesis [262]. 

Some variants of the above methods have been successfully utilized in total syntheses. For example, anomeric vinyl stannanes were found useful for coupling with suitable vinyl or aromatic iodides. This allowed the total synthesis of the anthracycline derivative vineomycinone B2 using palladium... 

Gyorkos, A. C., Stille, J. K., Hegedus, L. S. The total synthesis of ( )-epi-jatrophone and ( )-jatrophone using palladium-catalyzed carbonylative coupling of vinyl triflates with vinyl stannanes as the macrocycle-forming step. J. Am. Chem. Soc. 1990,112, 8465-8472. 

In situ synthesis of vinyl stannanes from alkynes [53] A solution of terminal alkyne (1.69 mmol), Pd2dba3 (0.0423 mmol) and lris(furyl)phosphine (P(fu)3, 0.169 mmol) in dry toluene (20 mL) -was stirred and cooled at 0 °C. To this solution was added tributyl tin hydride (1.69 mmol). After 5 min the cooling bath was removed and die reaction mixture stirred for another 2 h at r.t. This vinyl stannane solution can be used directly for Slide couplings. 

A recent application to the synthesis of the macrolide antibiotic concanamycin used carbo-metallation of the alkyne 141 to give the vinyl iodide -142 followed by a palladium-catalysed coupling with a vinyl stannane, also created from an alkyne, to give the diene34 , -143. 

Now let us look at a complete synthesis.28 The natural product pleraplysillin-1 199 is found in a marine sponge and in the nudibranch (a kind of apparently defenceless shell-less mollusc) that eats it. It has a defensive role - the nudibranch is rapidly rejected as a food source by carnivorous fish .29 Pleraplysilin-1 has a diene joined to a furan at the difficult 3-position. Disconnection between the two double bonds suggests a vinyl triflate 201 from a cyclic alkene, as we can make that regioselectively from the corresponding ketone, and a vinyl stannane from the furan half 200. 

Both syntheses made the bond between the two alkenes by a Stille coupling. One put the tin on the amide part by a Cu(I) catalysed conjugate addition of Bu3SnLi to the acetylenic ester 212 and Weinreb amide formation. Coupling this vinyl stannane with a single enantiomer of the iodide derived from the rest of the molecule gave crocacin C in good yield. The synthesis of the iodide uses an asymmetric aldol reaction and is described in the workbook.30... 

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