Allylstannanes radical reactions

Another class of compounds which undergo addition reactions with alkyl radicals are allylstannanes. The chain is propagated by elimination of the trialkylstannyl radical.229 230 231... 

In addition to allylsilanes, CM can also be applied to allylstannanes, which serve as valuable reagents for nucleophilic additions and radical reactions.To date, only eatalyst 1 has been shown to demonstrate CM reactivity in the preparation of 1,2-disubstituted allylstannanes, as ruthenium catalysts were found to be inactive in the presence of this substrate class.Poor stereoselectivities were generally observed, with the exeeption of one instance of >20 1 Z-selectivity in the reaction of allyltributylstannane with an acetyl-protected allyl gluco-side. 

Excellent yields and diastereoselectivities have been obtained in allylations using a new oxazolidinone chiral auxiliary derived from diphenylalaninol [24]. The use of oxazolidinone chiral auxiliaries was sparked by the application of Lewis acids to radical reactions. Bidentate Lewis acids are used to favor one rotamer (44) out of a possible four by forming a chelated intermediate with the two carbonyl groups and through steric interactions imparted by the 4-substituent of the oxazolidinone (Eq. (13.12)). Trapping with the allylstannane can then occur on the face opposite the bulky oxazolidinone-4-substituent. 

Allylstannanes work as allylating reagents under free-radical reaction conditions. Free-radical reactions have several advantageous features in organic synthesis -neutral reaction conditions, compatibility with Lewis acids, and no need to protect reactive functional groups such as hydroxy and amino groups. In these days, therefore, free radical allylation procedures have been widely used in organic synthesis and several reviews on free radical reactions are available [94]. 

Radicals bearing a chiral amide group, derived from Oppolzcr s camphor sultam, are intermediates in radical reactions with allylstannanes . The allylations yield the two isomeric products with high selectivities. 

The new diphenylalanine-derived oxazolidinone, 15, is particularly effective when used as an auxiliary on radical 29. The auxiliary can be used in a propagation sequence that involves radical addition followed by trapping of the addition radical with allylstannane or allylsilanes, Eq. (21). Excellent yield and diastereoselectivity are observed if the reaction is carried out in the presence of Lewis acids such as magnesium bromide or lanthanide triflates at —78°C. The reaction promoted by magnesium bromide, for example, provides a diastereomer mixture in excess of 100 1 with a yield of 85%. Sc, Yb, Y, La, or Sm triflates provide similar results in reactions usually carried out in ether. 

Interesting and novel cardon-cardon bond-forming radical reactions have been applied to halogenated derivatives, xanthate esters and related compounds. One paper describes the use of vinylstannanes which involves radical addition, elimination pro-cesses (Scheme 15) another uses allylstannanes (Scheme 16). 

The use of allylstannanes for homolytic allylation depends on the rapid conjugate displacement of R3Sn- by attack of a radical at the y-position of the allyl group. The rate constants for this reaction by primary alkyl radicals with the allylstannanes 22 and 23 in Scheme 9 are close to the value that was estimated previously for allyltributyltin.285,286... 

Stannyl radicals are usually generated by homolytic substitution at hydrogen in a tin hydride, or at tin in a distannane, or, conjugatively, at the y-carbon atom in an allylstannane.453 The initiator is commonly AIBN at ca. 80 °C. In the presence of a trace of air, organoboranes are oxidized by a radical chain mechanism, and triethylborane is now commonly used as an initiator at temperatures down to —78°C,519 and it can be used in aqueous solution.520 9-Borabicyclo[3.3.1]nonane (9-BBN) has similarly been used to initiate the reaction of tin hydrides at 0 and —78°C,521 and diethylzinc works in the same way.522... 

The radical source must have some functional group X that can be abstracted by trialkylstannyl radicals. In addition to halides, both thiono esters and selenides are reactive. Allyl tris(trimethylsilyl)silane can also react similarly.232 Scheme 10.11 illustrates allylation by reaction of radical intermediates with allylstannanes. 

Substitution at the terminal position of the allylstannane, as in crotonyltributyl stannane, however, is not tolerated, because hydrogen abstraction from the allylic position is a competing reaction [21], An extension of the method involves the coupling of the anomeric radical precursors 28 with the allyltributyltin reagent 29 [14], In the reagent 29 the double bond is activated toward addition of nucleophilic radicals by the electron-withdrawing t-butoxy carbonyl group. The obtained product 30 has been useful en route to 3-deoxy-D-marmo-2-octulosonic acid (KDO). 

The mechanism of this transformation is outlined in Scheme 38 and each step has important features. In step 1, the tributyltin radical abstracts the radical precursor X. A possible side reaction, the addition of the tributyltin radical to the allylstannane, is much slower than comparable additions to activated alkenes. Even if this addition occurs, the stannyl radical is simply eliminated to regenerate the starting materials. Thus, for symmetric allylstannanes, this reaction is of no consequence. As a result, the range of precursors X that can be used in allylation is more extensive than in the tin hydride method. Even relatively unreactive precursors like chlorides and phenyl sulfides can be used if they are activated by adjacent radical-stabilizing groups. 

A sequence of reactions that was recently reported by Hanessian and Alpegiani nicely illustrates how the allylstannane method is useful for functionalization of complex, sensitive substrates and, more generally, how stereochemistry can be controlled in radical addition reactions (Scheme 40).138 Dibromo- 3-lac-tam (25) can be monoallylated with a slight excess of allyltributylstannane and then reduced with tributyltin hydride to provide 3-allylated (3-lactam (26) (the acid salt of which shows some activity as a 3-lactamase inhibitor). Stereochemistry is fixed in the reduction step hydrogen is delivered to the less-hindered face of the radical. Alternatively, monodebromination, followed by allylation, now delivers the allyl group from the less-hindered face to provide stereoisomer (27). Finally, allylation of (25) with excess allylstannane produces the diallylated product (not shown). 

At present, bimolecular allylation is limited to unsubstituted and 2-substituted allylstannanes (which are symmetrical so that addition and elimination of a tin radical are degenerate). 1-Substituted allylstannanes (for example, crotylstannane) are not useful reagents because the substituent decelerates the rate of the radical addition step below the useful limit.139 The usefulness of 3-substituted allylstannanes has been limited by their relatively facile isomerization to the inert 1-substituted isomers under typical reaction conditions.140... 

Dussault and coworkers described the preparation of allylstannanes (116, 117) as part of their synthetic studies (equation 93)731. It is interesting to note the preferred geometries of the products which appear to be dependent on the nature of the stannane employed. In this last example, Yu and Oberdorfer reported the use of free-radical hydrostannylation in their preparation of (tributylstannyl)vinyl-substituted 2-deoxyuridine derivatives (e.g. 118) for use in halogenation and radiohalogenation reactions (equation 94)733. 

A complementary sequence uses an alkyl halide 7.46 with a Z-substituent to create an electrophilic radical 7.47 in the presence of a nucleophilic alkene 7.48. In this case, the radical 7.49 expels the low-energy tributyltin radical to regenerate the tin radical achieving overall the allylation of the ester, catalytic in both the AIBN and the tin hydride. The Z-substituent in the radical 7.47 is necessary for an efficient reaction—in its absence the allylstannane has to be used in large excess. 

In 1995, Porter et al. [34] reported the first excellent results for free radical addition to an electron-deficient alkene by use of chiral zinc complexes. Reaction of the oxa-zolidinone 9 with tert-butyl iodide and allyltributylstannane 30 in the presence of Zn(OTf)2 and a chiral bis(oxazoline) ligand 12 gave the adduct 44 in 92 % yield with 90 % ee (Sch. 18). The chiral bis(oxazoline) complexes derived from ZnCl2 or Mg(OTf)2 gave racemic products. In this reaction, lower allyltin/alkene ratios gave substantially more telomeric products, and a [3 + 2] adduct 45 of the oxazolidinone 9 and the allylstannane 30 was obtained at temperatures above 0 °C. 

Diastereoselective radical allylations have been studied in many different contexts, and a plethora of information exists regarding stereocontrol in these reactions. Allylations have been performed using the traditional trapping and )9-elimination sequence occurring typically with allylstannanes as well as a stepwise atom transfer/ elimination sequence found to occur with allylsilanes. Stereochemistry is commonly controlled through the use of chiral auxiliaries or by 1,2-induction, and functionalized anh -aldol and amino acid products are available using this established methodology. 

Highly diastereoselective allylations were also achieved in a slightly different manner through radical addition to chiral oxazolidinone acrylate and trapping with allylstannane [25]. In reactions with a,yS-unsaturated substrates, the Lewis acid... 

Strongly electron-deficient y9-ketoamidyi radicals on chiral oxazolidine auxiliaries have also been shown to trap allylstannanes with high levels of selectivity (Eq. (13.16), Table 13-5) [26]. High diastereoselectivity in these reactions is obtained with bulky R groups on the chiral auxiliary and by lower reaction temperatures. 

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