Allylations Sakurai

Related reactions Roush asymmetric allylation, Sakurai allylation ... 

Sakurai reactions proceed regiospecifically with a large variety of electrophiles due to the so-called /1-effect5-9. However, allylsilanes are also known as masked allyl carbanions, which may be activated by the presence of fluoride ion10-12. 

In the synthesis of spirocyclic systems via an intramolecular Sakurai reaction, allylsilanes with an allyl moiety attached to the 3-position of the 2-cyclohexenone are required as starting materials. 

In the presence of In powder 2-cycIohexen-l-one is converted by allyl iodide and Me3SiCI 14, in 63% yield, into the 1,4-addition product 2179 [84], which is also obtained in 73% yield by Sakurai 1,4-addition ofallyltrimethylsilane 82 to 2-cyclohexene-l-one in the presence of excess Me3SiCl 14 and catalytic amounts of InCl3 [85] (Scheme 13.25). Ytterbium] 111) triflate-catalyzed imino-ene reactions of N-tosylaldimines with a-methylstyrene are dramatically accelerated on addition of Me3SiCl 14 [85 a]. 

A variety of electrophilic catalysts promote the addition of allylic silanes to carbonyl compounds.86 The original catalysts included typical Lewis acids such as TiCl4 or BFj.87 This reaction is often referred to as the Sakurai reaction. 

Allylation of aldehydes or ketones using allylsilanes, known as the Hosomi-Sakurai reaction, is a useful method for obtaining homoallylic alcohols. TiIV compounds have been successfully applied to this reaction (Scheme 21) 80 Besides aldehydes and ketones, acylsilanes, 0,0-acetals, and A-,(7-acetals can be employed.81-83 1,4-Addition of an allyl group to an a,/ -unsaturated ketone has been also reported.84... 

Highly substituted 4-methylenetetrahydropyrans can be obtained from the allyl alcohol via its carbamate 20. Reaction of the derived allyllithium with aldehydes affords the (Z)-enolcarbamates 21 which undergo an intramolecular Sakurai cyclisation to the pyran as a single diastereoisomer (Scheme 11) <00TL7225>. 

General Procedure for the Silylformaltion/Sakurai Allylation. Synthesis of Polyol Fragments for Polyketide and Macrolide Synthesis. In a magnetically stirred stainless-steel Parr bomb the substrate (1 eq) is dissolved in benzene. The solution is cooled to - 78 °C until frozen. Rh(acac)(CO)2 (3 mol %) is then added and the Parr bomb is assembled and pressurized with CO (60 bar) and vented. This purge is repeated twice and the Parr bomb is pressurized with CO (60 bar) at - 78 °C. The apparatus is then immersed in an oil bath and heated at 60 °C for 22-24 h. After cooling to 0 °C, the bomb is vented. The solution... 

Enantioselective carbonyl allylation is one of the most broadly utilized transformations in synthetic organic chemistry (For reviews on enantioselective carbonyl allylation, see [199-204]). Shortly after the first reports of carbonyl allylation employing isolable aUylboron and allylsUicon reagents by Mikhailov and Bubnov [205] and Hosomi and Sakurai [206], respectively, enantioselective carbonyl allylations were reported by Hoffmann (see footnote 19, [207]). While the design of increasingly effective chiral allylmetal reagents continues 207-220], this... 

The introduction of the allylic silane moiety required for the intermolec-ular Hosomi-Sakurai reaction is depicted in Scheme 16. Following the formation of the enol triflate 97, a Stille coupling provided excess to the allylic alcohol 98 [51]. The allylic alcohol (98) was endowed with a phosphate leaving group for the subsequent allylic substitution. Utilizing a trimethylsilyl cuprate as nucleophile for the 5 2 reaction, the allylic phosphate was converted into the allylic silane 89. A useful substrate-induced diastereoselectivity in favour of (14i )-89 was encountered at small scale but decreased significantly upon up-scaling. 

The undefined mechanism of the aldol-type Mukaiyama and Sakurai allylation reactions arose the discussion and interest in mechanistic studies [143-145]. The proposed mechanism was proved to proceed through the catalytic activation of the aldehyde and its interaction with the silyl ketene acetal or allylsilane producing the intermediate. From that point the investigation is complicated with two possible pathways that lead either to the release of TMS triflate salt and its electrophihc attack on the trityl group in the intermediate or to the intramolecular transfer of the TMS group to the aldolate position resulting in the evolution of the trityl catalyst and the formation of the product (Scheme 51). On this divergence, series of experimental and spectroscopic studies were conducted. 

Bismuth Triflate-Catalyzed Sakurai Allylation Reaction. 71... 

Allyl- and vinylsilane chemistry was one of the first areas of reagent synthesis impacted by CM methodology. Allylsilanes are commonly employed in nucleophilic additions to carbonyl compounds, epoxides, and Michael acceptors (the Sakurai reaction) vinylsilanes are useful reagents for palladium-coupling reactions. As the ubiquitous application of CM to this substrate class has recently been described in several excellent reviews, this topic will not be discussed in detail, with the exception of the use of silane moieties to direct CM stereoselectivity (previously discussed in Section 11.06.3.2). 

Scott G. Nelson of the University of Pittsburgh has developed (J. Org. Chem. 2005, 70,4375) a highly diastereocontrolled route to substituted cyclohexanones using the intramolecular Sakurai reaction. The requisite ally silane 12 was prepared by Claisen rearrangement of the allylic alcohol 10, followed by homologation. The Ti enolate from the Sakurai addition was trapped with isobutyraldehyde to give 13. Although 32 diastereomers of 13 are possible, the diastereomer illustrated was the dominant product from the cylization. Note that use of the enantiomerically-pure form of the alcohol 10 would have led to enantiomerically-pure 13. 

This reaction, also, has been performed diastereoselectively.461 Allylic silanes R.2C=CHCH2SiMe3 can be used instead of silyl enol ethers (the Sakurai reaction). 462 Similarly, silyl ketene acetals, e.g., 56, give 8-keto esters, in MeN02 as solvent, for example,463... 

Intramolecular Sakurai reaction. Allylic and propargylic silanes can undergo a Lewis acid catalyzed intramolecular Sakurai reaction.1 In cyclization to hydrin-danones, the stereochemical outcome can differ from that obtained by fluoride ion catalysis (presumably kinetically controlled cyclization), equation (I).2... 

The Lewis acid catalyzed conjugate addition of allylsilanes (140) to (142) and allylstannanes (154) and (155) to ot,0-enones, described by Sakurai,68a,68b is highly efficient and experimentally simple in contrast to the allylcuprate additions. Various substituents can be incorporated into the allylsilanes (allylstannanes), e.g. alkoxy, alkoxycarbonyl and halogen, some of which are incompatible with cuprate reagents 69 In addition, Heathcock and Yamamoto report that diastereoselectivity is correlated to the alkene geometry of both the allylmetals and the acceptor units for example, allylation of ( )-enones (143) and (146) affords predominantly the syn adducts (144) and (147), while (Z)-enone (149) gives predominantly the anti adduct (150 Scheme 25).680 On the other hand, with cyclohexen-2-one the (Z)-silane (141) affords predominantly the threo adduct (152), while (142) affords erythro adduct (ISS).686 The more reactive allylstannanes (154) and (155) also afford similar diastereoselectivity.68e,f... 

It has also been shown that the Sakurai-Hosomi reaction of methallylsilanes with glyoxylates is catalyzed by the BINOL-Ti complex (1) to give the products, surprisingly, in an allylic silane (ene product) form with high enantioselecdvity (Scheme 8C.22) [53],... 

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