Allylation reaction using allyltributyltin

Cd. Cadmium perchlorate was found to catalyze allylation reactions using allyltributyltin in aqueous media very efficiently.177 These cadmium-catalyzed allylation reactions are accelerated by ligands such as N, N, N, N", A -pentamethyldicthylcnetri amine or 2,9-dimethylphenanthroline (Eq. 8.75). This accelerated the catalytic system to give allylation products of various aldehydes and ketones in high yields. 

Cesarotti and coworkers have developed an allylation reaction using allyltribu-tyltin in the presence of an AgOTf-BITIANP complex.7 In one example, the reaction was conducted with 4-bromobenzaldehyde and allyltributyltin in the presence of the catalyst to give the adduct with 78% ee (Scheme 9.3). 

Keck almost simultaneously reported two procedures using chiral titanium catalysts 6A and 6B for the enantioselective addition of allyltributyltin to aldehydes [11]. In the first procedure, the catalyst 6A is prepared from a 1 1 mixture of (R)-binaphthol and titanium tetraisopropoxide. The second procedure for the preparation of 6B, in contrast, requires a 2 1 mixture of BINOL, Ti(0 Pr)4, and a catalytic amount of CF3SO3H or CF3CO2H. Using 10 mol % of the catalyst 6A or 6B, a variety of aromatic, aliphatic, and a,P-unsaturated aldehydes are efficiently transformed into the corresponding optically active homoallylic alcohols with high enantioselectivity. An improved procedure was later published for the catalytic asymmetric allylation reactions using the 2 1 BINOL/Ti catalytic system [12]. 

More recently, Benaglia and coworkers reported that the allylation reaction of a-iminoesters proceeded to give the homoallyl alcohols with moderate enantioselectivities (Scheme 9.4).9 The chiral diimine that has a chiral 1,2-cyclohexyldiamine framework was used as the ligand. The reaction of a-iminoesters and allyltributyltin in the presence of AgOTf and diimine ligand proceeded to afford chiral amino acid derivatives with moderate enantioselectivities. 

Allyltributyltin (5) is the most commonly used reagent for carrying out allylation reactions via a free radical fragmentation process [5]. Keck reported the first practical use of allyltributyltin for free radical allylation reactions in 1982 in the context of a synthesis of perhydrohistrionicotoxin [6]. Heating bromide 4 with allyltributyltin in the presence of AIBN as a radical initiator gave the allylated derivative 6 (Scheme 3) in high yield with complete control of stereochemistry. Similar transformations had proven to be very difficult by standard ionic reactions. 

A series of aryl radical cyclizations were reported by a group at Novartis [10], and some of these processes were also compared with bond formation by Pd-mediated Heck cyclization of the same substrates. The tributyltin hydride-mediated reaction of iodo alkenes 7 (Scheme 3), immobilized on polystyrene resin through a linker, gave dihydrobenzofurans 8 [11]. It was also possible to perform a tandem cyclization using allyltributyltin to give the allylated product 9, although the yields were less satisfactory. The radical cyclization onto enol ethers was demonstrated [12] by the conversion of 10 to 11. For best results, the tributyltin hydride and AIBN were added portionwise every 5-8 h. The impressive 95% yield was in fact higher than that for the solid-phase Heck cyclization of 10. Similarly, cyclization of anilide 12 afforded the phenanthridine 13. 

One of the more commonly used organotin reagents in both free-radical reactions and Lewis acid-mediated reactions is allyltributyltin [3, 7]. This reagent permits the construction of new carbon-carbon bonds from free radical precursors such as alkyl halides however, reactions with a-ketocydopropanes were poorly understood. Tin(IV) enolates generated from a-ketocyclopropane 44 and allyltributyltin undergo both radical allylation and electrophilic quench as shown in Scheme 11, forming O-stannyl ketyl 45 with allyltributyltin and subsequent scission of the cyclopropane... 

Sibi et al reported the first example in acyclic systems where both highly diastereo-and enantioselective tandem radical reactions occurred with carbon-carbon bond formation to achieve the vicinal functionalization of cinnamates with chiral Mg(II) catalysts (Scheme 4.5) [3]. The reactions began with the addition of nucleophilic alkylradical to cinnamate (7) and trapping of the intermediate radical with allyl-stannane using a chiral bis(oxazoline)s-Mgl2 as a Lewis acid. The reaction with cinnamate (7) (1 equiv), t-Bul (10 equiv), allyltributyltin (5 equiv), and triethylborane... 

Bednarski has reported that this allylation reaction has been used for the key step in the synthesis of C-glycoside derivatives of sialic acids, which are the carbohydrate groups found at the terminal sites of cell-surface glycoproteins and glycolipids. Thus, the allylation of glycosyl chloride 16 with allyltributyltin under photo irradiation in the presence of hexabutylditin followed by hydrolysis gives an approximate 1 1 mixture of the a- and P-isomers. It is worth mentioning that while several synthetic approaches by... 

Isoquinoline alkaloids. The regioselective allylation of N-acyl heterocycles (13, 10) can be used for synthesis of isoquinoline alkaloids. Thus simultaneous reaction of the dihydroisoquinoline (1) with a diunsaturated acyl chloride (2) and allyltributyltin affords the 1,2-adduct (3), which undergoes a Diels-Alder cyclization... 

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... 

A chiral dinuclear Ti(IV) oxide 20 has been successfully designed by Maruoka and coworkers and can be used for the strong activation of aldehydes, thereby allowing a new catalytic enantioselective allylation of aldehydes with allyltributyltin (Scheme 12.18). ° The chiral catalyst 20 can be readily prepared either by treatment of bis(triisopropoxy)titanium oxide [(/-Pr0)3Ti-0-Ti(0/-Pr)3] with (S)-BINOL or by the reaction of ((5)-binaphthoxy)isopropoxytitanium chloride with silver(I) oxide. The reaction of 3-phenylpropanal with allyltributyltin (1.1 equiv) under the influence of 20 (10 mol%) gives l-phenyl-5-hexen-3-ol... 

By far the most generally useful synthetic application of allyltributyltin is in the complementary set of transition metal- and radical-mediated substitution reactions. When the halide substrates are benzylic, allylic, aromatic or acyl, transition metal catalysis is usually the method of choice for allyl transfer from tin to carbon. When the halide (or halide equivalent) substrate is aliphatic or alicyclic, radical chain conditions are appropriate, as g-hydrogen elimination is generally not a problem in these cases. 

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). 

Allylation of these P-alkoxy-a-halo esters with allyltributyltin initiated with AIBN at 60° also shows good to impressive stereoselectivity, which can be improved by use of triethylborane as initiator at —78°. However, these reactions are generally slower than radical reductions. 

A similar chiral silver(I) catalyst 21 was applied to the asymmetric addition of allyltributyltin to various aldehydes in an aqueous medium [28]. Shi et al. have shown that chiral silver complex 22, prepared from chiral bidentate phospho-ramide and AgOTf, is also an effective chiral catalyst for the allylation [29]. Chiral bis(oxazoline) ligands have found widespread use in asymmetric reactions catalyzed by chiral metal complexes, and C2-symmetric chiral bis(oxazoline)-Zn(OTf)2 complex 23 has been applied to catalytic enantioselective allylation of aldehydes with allyltributyltin (44) however, satisfactory enantioselectivity was not observed [30]. 

The use of chiral auxiliaries proved to be particularly efficient for the preparation of optically pure materials via radical reactions [29]. Yamamoto et al. [30] examined the free-radical reaction of an a-bromoglycine derivative 35 having a chiral auxiliary with allyltributyltin 30 to give allylated product 36 (Sch. 14). Although the use of 0.1 equiv. 

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