Keck allylation reaction additives

The addition processes are characterized as Type II allylation reactions and featnre open transition states. Denmark and Keck have described mechanistic studies, which have provided basic information shaping current views regarding the Type II allylations of organostannanes. Denmark s models are briefly summarized by the cyclization of deuterium-labeled 4 (Scheme 5.2.2). Intra-molecular allylation proceeds with Lewis and Brpnsted acids to yield 6 with high selectivity. The alcohol 6 is rationalized throngh the synclinal transition state 5 via anti-Su substitution. To a lesser degree, various Lewis acids also produce the... 

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]. 

Keck reported an asymmetric allylation with a catalytic amount of chiral titanium catalyst [24]. The enantioselective addition of methallylstannane to aldehydes is promoted by a chiral catalyst 13 prepared from chiral BINOL and Ti(0-i-Pr)4 (Scheme 9.10). An example of asymmetric amplification was reported by using (R)-BINOL of 50% ee, and the degree of asymmetric amplification was dependent on the reaction temperature. Tagliavini also observed an asymmetric amplification in the enantioselective allylation with a BIN0L-Zr(0-i-Pr)2 catalyst [25]. 

The transmetallation or the metal-metal exchange reaction of an allylic tin species with an electrophile was first observed in 1970 [77]. The possibility that transmetallation may play a role in the Lewis acid-promoted reaction of allylstannanes with aldehydes was initially discussed by Tagliavini [78], Keck [79], Yamamoto [71b, 80], and Maruyama [81]. It is believed that upon transmetallation with either SnCU or TiCl4, the addition of an allylstannane and aldehyde will occur via a cyclic, six-membered transition structure. The reaction occurs by coordination of the aldehyde carbonyl with the Lewis acidic trichlorotin or trichlorotitanium reagent, thus affording the anti homoallylic alcohol (Scheme 10-42). 

A related Mukaiyama aldol catalyst system reported by Keck prescribes the use of a complex that is prepared in toluene from (R)- or (S)-BINOL and Ti(0 Pr)4 in the presence of 4 A molecular sieves. In work preceding the aldol addition reaction, Keck had studied this remarkable catalyst system and subsequently developed it into a practical method for enantioselective aldehyde allylation [95a, 95b, 95c, 96]. Because the performance of the Ti(IV) complex as an aldol catalyst was quite distinct from its performance as a catalyst for aldehyde allylation, a careful examination of the reaction conditions was conducted. This meticulous study describing the use of (BINOL)Ti(OiPr)2 as a catalyst for aldol additions is noteworthy since an extensive investigation of reaction parameters, such as temperature, solvent, and catalyst loading and their effect on the enantiomeric excess of the product was documented. For example, when the reaction of benzal-dehyde and tert-butyl thioacetate-derived enol silane was conducted in dichlo-romethane (10 mol % catalyst, -10 °C) the product was isolated in 45% yield and 62% ee by contrast, the use of toluene as solvent under otherwise identical conditions furnished product of higher optical purity (89% ee), albeit in 54% yield. For the reaction in toluene, increasing the amount of catalyst from 10 to 20 mol %... 

Driven by the inability to substitute allyltin compounds at the 3-position, Keck examined intermolecular addition reactions of allyl sulfides [50]. He was able to show that 3-methyl- and 3,3-dimethyl-substituted allyl phenyl sulfides 86 and 88 undergo reaction with alkyl halides and alkyl phenyl selenides in the presence of hexabutylditin to form good yields of the allylation products (Scheme 18). These... 

C-Glycopyranosides may be obtained from glycopyranosyl halides via intermolecular addition of glycopyranosyl radicals [129]. In a more useful example, the a-aminoacrylate 192 was used as the radical acceptor for preparation of C-glycosyl amino acids 193 and 194 [130] (Scheme 66). In a concise synthesis of showdomycin (197), Barton utilized the trigger reaction of the 7V-hydroxy-2-thiopyridone derivative and the exceptional radicophilicity of tellurides in concocting the conditions for the conversion from the anisyl telluride 195 to the intermediate 196 after oxidative elimination [131] (Scheme 67). In Keck s synthesis of (-t-)-pseudomonic acid C (201), the intermediate 200 was prepared via stereocontrolled intermolecular addition of the radical generated from the iodide 198 to the allylic sulfone 199 [132] (Scheme 68). 

The Keck reaction can be accelerated by using additives, which facilitate the equilibria leading to the regeneration of the catalyst 28. Walsh found that isopropanol increases the rate and the enantioselectivity of the allylation of... 

The first reports of radical addition-fragmentation processes appeared in the synthetic organic chemistry literature in the early 1970s. Well-known examples of processes that involve a reaction step with an Sh2 mechanism include allyl transfer reactions with allyl sulfides and stannanes (the Keck... 

In conclusion, the Sakurai reaction is a powerful method to introduce a nucleophilic allyl synthon. Similar allylations include the Keck reaction of allylstannanes, and the Roush reaction of allylboranes. What sets the Sakurai reaction apart is the exceptional stability of allylsilanes, which are stable to air and water, and can easily be chromatographed, unlike most other allylmetal species. In addition, allylsilanes are easily accessible by a variety of reactions. These factors have allowed the Sakurai reaction to find widespread use, from basic methodology to total synthesis. 

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