Allylstannanes with radicals

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. 

One of the most synthetically valuable reactions of tetraorganostannanes is the ally-lation which includes homolytic cleavage of allyl-tin bonds. The radical chain reactions of allylstannanes with alkyl halides and sulfides effected with radical initiators or photoirradiation afford the corresponding substitution products (eq (110)) [105]. 

Allylstannanes are much better nucleophiles for dithioacetals than allylsilanes, and dimethyl(methyl-thio)sulfonium fluoroborate is a particularly good catalyst in this reaction. The reaction has been used tellingly in a macrocyclization (Scheme 56). ° Monothioacetals also react with allylstannanes, with cleavage of either the carbon-oxygen or the carbon-sulfur bond, depending upon the choice of Lewis acid (Scheme 57).Sugar thioacetals react in the same way (Scheme 58), but with the opposite anomeric stereoselectivity from that of the corresponding radical chain substitution. ... 

The radical 28 reacts with alkenes, PTOC esters, and allylstannane with good selectivity. The oxazolidine with Ri = t-Bu is particularly effective as an auxiliary group. Thus, the radical 28 having R = (C6Hn)CH2 and Rj = -Bu reacts with allytributylstannane with a selectivity greater the 20 1 at 80 °C, and its reaction with PTOC esters gives a 60 1 mixture of thiopyridyl ester products at room temperature. 

Allyltributylstannanes are common reagents in both radical and Lewis acid-mediated reactions, although they are unknown to react with enones. However, there has been the first report of a reaction of an electrophilic allylstannane with an enone (Scheme 1). While the parent allylstannane does not react with enones, those substituted with an ester substitute smoothly at the y3-position of enones. The authors claim this to be the first non-basic and non-nucleophilic alternative to the Michael reaction. 

A useful synthesis of allylstannanes from primary alcohols involves conversion of the alcohols into their O-substituted 5-methyl carbonodithioates, thermolysis to effect [3,3] rearrangement to the corresponding 5-substituted 5-methyl carbonodithioates, and treatment with a trialkyl-tin hydride under free-radical conditions to form the allylstannane21. This procedure has been applied to the synthesis of functionalized allylstannanes including (5)-( )-4-(benzyloxy)-2-pen-tenyl(tributyl)stannane22. 

Allylstannanes are also available from allyl sulfoncs24 and sulfides25 by treatment with tri-alkyltin hydrides under free-radical conditions. Of some interest is the stereocontrol exercised by a neighboring hydroxy group, possibly because of interaction with the tin26. 

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... 

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... 

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. 

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. 

Derivatives of trifluoroethanethiol have limited though interesting chemistry. Unfortunately, metallated difluorothioenol chemistry has not been reported, because rapid nucleophilic attack occurs even by hindered bases such as LDA. Nakai et al. exploited this high electrophilicity in a tandem addition/elimina-tion-rearrangement sequence [146], but more recent applications have concerned free radical chemistry (Eq. 46). Chlorination of trifluoroethyl phenyl sulfide followed by exposure to tin hydride in the presence of an allylstannane resulted in C-C bond formation with a reasonable level of stereocontrol [147]. 

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). 

Radical prenylotion.2 The allylstannane corresponding to 1 cannot be used for radical prenylation because of facile isomerization. However, prenylation of alkyl halides can be effected by irradiation of 1 (3 equiv.) and hexabutylditin (1.5 equiv.) Presumably 1 reacts with Bu3Sn to form an allylstannane. The yields of this process are not as high as those observed with allyltributyltin (11, 15-16). 

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). 

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. 

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. 

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... 

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