Stannanes, addition

In general, allenic silanes are less reactive than their stannane counterparts. Whereas allenic stannane additions to aldehydes are promoted by the comparatively mild Lewis acid BF3 OEt2 or even MgBr2, the corresponding silanes require TiCI4 or AICI3. Some of the early studies are summarized in Table 9.38 [52],... 

C-Glycoside synthesis may be achieved in twro ways. Intermolecular radical addition reactions are observed with (i) polarized, electron-deficient alkenes, (ii) alkenes that provide a high level of stabilization to the initial radical adduct and (in) substrates that undergo a facile fragmentation (e.g. allyl stannanes). Additions to less reactive substrates, though not favored for intermolecular processes, are observed if the two components are tethered in an intramolecular array. 

The first studies on Lewis acid promotion of allylic stannane additions were conducted with BF3 OEt2 (Table 4) [13]. Aldehydes were found to be more reactive than ketones and methyl ketones were more reactive than internal ketones. Addition to 4-fert-butylcyclohexanone favored equatorial allylation by 85 15. 

The first Lewis acid-promoted intramolecular addition reaction was conducted as part of a study designed to ascertain the transition-state geometry of allylic stannane additions to aldehydes (Table 45) [77]. 

The preparation34 of the left half of cephalostatin 7 was more straightforward. Compound 56, the minor product of the stannane addition (Scheme 25, vide supra) was deoxygenated by Barton s xanthate procedure (Scheme 28) to give 60, which was stereoselectively dihydroxylated using the Sharpless AD-mix-a reagent35 to yield 61 and its inseparable C-25 epimer in a 2.5 1 ratio. 

The total synthesis of Epothilone B 4, the first natural product (with Epothilone A) to show the same microtubule-stabilizing activity as paclitaxel (Taxol ), has attracted a great deal of attention since that activity was first reported in 1995. The total synthesis of 4 devised J. Org. Chem. 2008, 73, 9675) by Gary E. Keck of the University of Utah was based in large part on the stereoselective allyl stannane additions (e.g. 1 + 2 3) that his group originated. 

Lithiation at C2 can also be the starting point for 2-arylatioii or vinylation. The lithiated indoles can be converted to stannanes or zinc reagents which can undergo Pd-catalysed coupling with aryl, vinyl, benzyl and allyl halides or sulfonates. The mechanism of the coupling reaction involves formation of a disubstituted palladium intermediate by a combination of ligand exchange and oxidative addition. Phosphine catalysts and salts are often important reaction components. 

Stannanes also add across double bonds offiuonnated olefins in a free radical reaction Trimethylstannane undergoes stereospecific addition to hexafluorocyclo-butene to afford trans 1,2,3,3,4,4 hexafluoro 1 (trimethylstannyl)cyclobutane [5] (equation 1)... 

Tin/lithium exchange on the a-alkoxy stannanes and subsequent addition of carbon dioxide led to optically active (7-protected a-hydroxy acids 18 with retention of configuration and without any loss of stereochemical information11. 

In Lewis acid catalyzed carbonyl additions of allylsilanes and -stannanes, syn diastereoselectiv-ity predominates, irrespective of the double-bond configuration, indicating that open-chain transition states are involved. 

The best procedure reported to date for the asymmetric allylation of aldehydes using tributyl(2-propenyl)stannane involves the catalyzed addition with the BINOL-TiCl2 complex as catalyst. Good yields and ee s were obtained for both aromatic and aliphatic aldehydes using 20 mol% of the catalyst127. 

Tributyl[( )-l-(methoxymethoxy)-2-butenyl]stannane (4) is available by the addition of tri-butyltin lithium to 2-butenal followed by treatment with chloromethoxymenthane 03. The resulting diastereomers were separated by chromatography to give stereochemically homogeneous a-alkoxystannanes 5 and 6104. 

Stannylation of lithiated allyl ethers gives (Z)-3-alkoxyallylstannanes (1)115,116, whereas mixtures of (Z)- and ( )-tributyl(3-methoxy-2-propenyl)stannanes (2) were obtained from free-radical addition of tributyltin hydride to l-methoxy-l,2-propadienel16. 

Table 7. 4-Hydroxy-l-alkcnyl Diisopropylcarbamates from 2-Alkenyl Diisopropylcarbamates by Ho-moaldol Addition of Carbonyl Compounds to Trichlorotitanates (via Stannanes)...

The stannanes (-)-ent-12 and ( + )-ent- 3 (R = CH3) are obtained with >80% ee from the alkenyllithium (-)-sparteine complex105,107a (Section 1.3.3.3.1.1.). Hence, their titanium(IV) chloride mediated carbonyl additions are accompanied by chirality transfer and enantioface selection of opposite sense. This was demonstrated for the reaction with (5)-2-benzyloxy-propanal107b the d.r. (88 12) roughly reflects the enantiomeric composition of the stannanes. 

Stannane 6a underwent facile transmetalation in tetrahydrofuran at — 78 °C on treatment with butyllithium to afford 6b. Addition of the lithium reagent 6b to a solution of 1.1 equivalents of copper(I) bromide-dimethyl sulfide in 1 1 diisopropyl sulfide/tetrahydrofuran at — 78 °C gave the copper reagent 6c, which reacted with methyl vinyl ketone at —78 "C in the presence of boron trifluoride-diethyl ether65, producing 7 in 55% yield65. 

In contrast, a-alkoxycuprate 10, prepared from the corresponding stannane, gave the conjugate addition product with only 0-20% ee upon treatment with 2-cyclohexenone in the presence ofchlorotrimethylsilane67. However, the conjugate addition of 10 to ethyl propynoatc in the presence of chlorotrimethylsilane provided 11 in 85% yield with nearly 96% ee67. 

In addition to the radical ipso-substitution of indolyl sulfones producing stannanes described earlier <96T11329>, Caddick has also reported an approach to fused [l,2-a]indoles based on the intramolecular cyclization of alkyl radicals. Thus, treatment of 112 with BuaSnH leads to the fused ring derivatives 113 (n = 1-4) <96JCS(P1)675>. 

Allyl carbamates also can serve as amino-protecting groups. The allyloxy group is removed by Pd-catalyzed reduction or nucleophilic substitution. These reactions involve formation of the carbamic acid by oxidative addition to the palladium. The allyl-palladium species is reductively cleaved by stannanes,221 phenylsilane,222 formic acid,223 and NaBH4,224 which convert the allyl group to propene. Reagents... 

Allylic derivatives are particularly important in the case of boranes, silanes, and stannanes. Allylic boranes effect nucleophilic addition to carbonyl groups via a cyclic TS that involves the Lewis acid character of the borane. 1,3-Allylic transposition occurs through the cyclic TS. 

The readily available organotin compounds include tin hydrides (stannanes) and the corresponding chlorides, with the tri-n-butyl compounds being the most common. Trialkylstannanes can be added to carbon-carbon double and triple bonds. The reaction is usually carried out by a radical chain process,137 and the addition is facilitated by the presence of radical-stabilizing substituents. 

Palladium-catalyzed procedures have also been developed for addition of stannanes to alkynes,143 and these reactions usually occur by syn addition. 

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