Homoallyl alcohols allylsilanes

Si. rra(pentafluorophenyl)boron was found to be an efficient, air-stable, and water-tolerant Lewis-acid catalyst for the allylation reaction of allylsilanes with aldehydes.167 Sc(OTf)3-catalyzed allylations of hydrates of a-keto aldehydes, glyoxylates and activated aromatic aldehydes with allyltrimethylsilane in H2O-CH3CN were examined. a-Keto and a-ester homoallylic alcohols and aromatic homoallylic alcohols were obtained in good to excellent yields.168 Allylation reactions of carbonyl compounds such as aldehydes and reactive ketones using allyltrimethoxysilane in aqueous media proceeded smoothly in the presence of 5 mol% of a CdF2-terpyridine complex (Eq. 8.71).169... 

Recently, a new multicomponent condensation strategy for the stereocontrolled synthesis of polysubstituted tetrahydropyran derivatives was re-published by the Marko group, employing an ene reaction combined with an intramolecular Sakurai cyclization (IMSC) (Scheme 1.14) [14]. The initial step is an Et2AlCl-promoted ene reaction between allylsilane 1-50 and an aldehyde to afford the (Z)-homoallylic alcohol 1-51, with good control of the geometry of the double bond. Subsequent Lewis acid-media ted condensation of 1-51 with another equivalent of an aldehyde provided the polysubstituted exo-methylene tetrahydropyran 1-53 stereoselectively and... 

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... 

In reactions of chiral aldehydes, TiIV compounds work well as both activators and chelation control agents, a- or A-oxygcnated chiral aldehydes react with allylsilanes to afford chiral homoallylic alcohols with high selectivity (Scheme 22).85 These chiral alcohols are useful synthetic units for the synthesis of highly functionalized chiral compounds. Cyclic chiral 0,0- and A/O-acetals react with allylsilanes in the same way.86,87 Allenylsilanes have also been reported as allylation agents. 

A norpseudoephedrine auxiliary has been used to achieve >98% ee in the preparation of homoallylic alcohols from aliphatic alcohols and allylsilane. On-line NMR spectroscopy has been used to shed light on the mechanism, including a diversion that occurs if the temperature is not kept low enough. 

The enantioselective addition of an allylsilane to an aldehyde catalyzed by chiral acyloxyborane (CAB) 13 is an excellent method for obtaining optically active homoallyl alcohols.Itsuno and Kumagai reported that the synthesis of a new optically active polymer with chirality on the mainchain is possible by applying this reaction to the asymmetric polymerization of bis(allylsilane) and dialdehyde (Scheme 12.11). ... 

Significantly better results in addition of non-stabilized nucleophiles have come from hydrogenolysis reactions using formate as a hydride donor as shown in Scheme 8E.46. The racemic cyclic acetate and prochiral linear carbonates were reduced in good enantioselectivities by monophosphine ligands (/ )-MOP (16) and (Zf)-MOP-phen (17), respectively [195]. The chirality of the allylsilane can be efficiently transferred to the carbinol center of the homoallylic alcohol by the subsequent Lewis acid catalyzed carbonyl addition reaction 1196], The analogous... 

The nature of the Lewis acid catalyst has been found to play a pivotal role in the chemo- and stereoselectivities of the Sakurai-Hosomi reaction. For example, the reaction of 33, which contains both allylsilane and allylstannane moieties, with benzaldehyde leads to the silyl-substituted homoallylic alcohol 34 in moderate yield when a mild Lewis acid such as Et3Al is used. On the other hand, when BF3 OEt2 or fluoride ion is employed,... 

The reaction of (Z)-/J-methylcrotylsilane with 2-benzyloxypropanal in the presence of chelative SnCL gives the awfi-homoallylic alcohol 40 diastereoselectively (equation 26)78. The use of chelative TiCLt versus nonchelative BF3 OEt2 Lewis acids also gives different stereoselectivity in the coupling of allylsilane with the aldehydes 41 (equation 27)79. 

A highly selective synthesis of homoallylic alcohols has been reported by Tietze et al.,917 who reacted methyl ketones, the chiral norpseudoephedrine derivative 285, and an allylsilane in the presence of a catalytic amount (0.2 mol%) of triflic acid [Eq. (5.340)]. The transformation was interpreted as an SN2 attack of the allylsilane to the protonated mixed acetal 286. The obtained ethers were then cleaved to the final product, homoallylic alcohols. 

The (F,)- and (Z)-(R)-allylsilanes (3b) react with aldehydes to give optically active (F)-homoallylic alcohols 5 or 6. In reactions with (E)-3b, essentially only the erythro-diustcreoisomer 5 is formed, regardless of the aldehyde used. In reactions with (Z)-3b, both vrythro and fAmi-diastereoisomers (6) are obtained, the ratio depending on the itructiircol the aldehyde but the configuration at C, is identical in both products and... 

In 1982, Sakurai [7] described a catalytic version of this reaction (Scheme 13.4). The addition of small quantities of fluoride anions to the allylsilane 1 generates the pentacoordinated silicon species 10, probably in equilibrium with the starting materials 1 and 11. This activated species can react with the carbonyl derivative 6 to yield the alkoxide 12 which is trapped by fluorotrimethylsilane. This last step not only furnishes the silylated compounds 13 but also regenerates the fluoride catalyst 11. Acidic work-up then leads to the desired homoallylic alcohol 7. 

Acetals and ketals 14 are the most often used precursors for the generation of oxonium species 16. Their main advantages lie in their resistance towards various basic reagents, their easy conversion into the desired oxonium intermediates in the presence of a suitable Lewis acid and in their ability to produce, by reaction with allylsilanes, enantiomerically pure homoallylic alcohols 26. For example, both enantiomers of 26 can be obtained starting from the enantiopure acetals 24 (Scheme 13.11). 

In summary, the SMS reaction is a truly efficient process, possessing a broad scope and applicable to a number of carbonyls, allylsilanes, alcohols (silyl ethers) or amines. Its usefulness has been validated in several total syntheses and demonstrated by the preparation of chiral homoallylic alcohols. During the development of the SMS reaction, Melkafia and Marko [48] realized that the homoallylic alcohol (ether), if connected to an allylsilane, would form novel annelating agents that would lead to tetrahydropyran derivatives via condensation with carbonyl compounds. This reaction was called IMSC for intramolecular Sakurai cydization and will be discussed in the next section. 

The same allyl-metallation protocol can be used for the preparation of allylstan-nane 191. Taking advantage of the greater nucleophilic propensity of the allylstan-nane function over the allylsilane one, 191 was treated with various aldehydes in the presence of Et20BF3, affording the homoallylic alcohols 192 in excellent yields (Scheme 13.67) [86]. It is noteworthy that complete syn-stereocontrol is observed in all these transformations. 

Several methods promoted by a stoichiometric amount of chiral Lewis acid 38 [51] or chiral Lewis bases 39 [52, 53] and 40 [53] have been developed for enantioselective indium-mediated allylation of aldehydes and ketones by the Loh group. A combination of a chiral trimethylsilyl ether derived from norpseu-doephedrine and allyltrimethylsilane is also convenient for synthesis of enan-tiopure homoallylic alcohols from ketones [54,55]. Asymmetric carbonyl addition by chirally modified allylic metal reagents, to which chiral auxiliaries are covalently bonded, is also an efficient method to obtain enantiomerically enriched homoallylic alcohols and various excellent chiral allylating agents have been developed for example, (lS,2S)-pseudoephedrine- and (lF,2F)-cyclohex-ane-1,2-diamine-derived allylsilanes [56], polymer-supported chiral allylboron reagents [57], and a bisoxazoline-modified chiral allylzinc reagent [58]. An al-lyl transfer reaction from a chiral crotyl donor opened a way to highly enantioselective and a-selective crotylation of aldehydes [59-62]. Enzymatic routes to enantioselective allylation of carbonyl compounds have still not appeared. 

Asymmetric hydrosilylation of 1,3-dienes provides convenient access to optically active a-chiral allylsilanes.107 1073 1071 The combination of 7r-allylpalladium chloride dimer with axially chiral monophosphine ligand 17 realizes high catalytic activity and enantioselectivity in the reaction of cyclic 1,3-dienes with HSiCl3.108,108a The allyltrichlorosilanes obtained react with aldehydes in a syn-Se mode to give homoallyl alcohols with high diastereo-and enantioselectivity (Scheme 9). 

Indium-mediated allylation of trialkyl(difluoroacetyl)silane 70 in aqueous media gives homoallylic alcohol 71 exclusively (Scheme 60). Both water and THF are essential for the allylation reaction. It is worth noting that homoallylic alcohol 71 is formed exclusively under these reaction conditions. On the contrary, enol silyl ether 72 is a major product of the fluorinated acylsilanes reaction with other organometallic compounds than indium via a Brook rearrangement and defluorination. Indium-mediated allylsilylation of carbonyl compounds provides a facile route to 2-(hydroxyethyl)allylsilanes. The allene homologs are similarly prepared (Scheme 61).244,244a... 

Homoallylic alcohols In the presence of this salt, allylsilanes (for example, 1) react with aldehydes or ketones to form, after hydrolysis, homoallylic alcohols (2). 

A different usage of such oxazin-l,4-diones in synthesis is exemplified by the preparation of the enantiomerically pure acyloin (417). The S-proline derivative (413) was treated with an allylsilane in the presence of a Lewis acid to give a mixture of optically active tertiary homoallyl alcohols... 

Condensation of achiral aldehydes with allylsilanes promoted by CAB catalyst (2) (20 mol %) at —78 °C in propionitrile produces homoallylic alcohols with excellent enantioselectivity (eq 7). 

Allystannanes are more nucleophilic than allylsilanes. Addition of achiral allylstannanes to achiral aldehydes in the presence of (1) (20 mol %) and Trifluoroacetic Anhydride (40 mol %) also affords homoallylic alcohols with high diastereo- and enantioselectivities (eq 8). 

Similar reactions, but not accompanied by the silyl migration, have also been reported. When a bulky allylsilane is reacted with benzoylformates, the product obtained is an oxetane, as shown in Eq. (100) [270]. If this reaction is executed with allyltrimethylsilane, the expected homoallyl alcohol is produced in good yield. When, moreover, interception of the /3-silyl cation with a neighboring nucleophile is faster than desilylation, even the trimethylsilyl group is preserved in the product (Eq. 101) [271]. 

C(3)-substituted allylsilanes (crotylsilanes) participate in chelation-controlled addition reactions with aldehydes to give syn addition products as the major stereoisomers. Generally, the ( )-crotylsilanes are highly selective in the syn sense (>9S 5). In contrast, the (Z)-crotylsilanes are much less selective (60-70 40-30 syn anti Scheme 42). Hayashi and Kumada have report a successful approach to optically active homoallyl alcohols using this strategy. They have reported that useful levels of asymmetric... 

A convergent total synthesis of 15-membered macrolactone, (-)-amphidinolide P was reported by D.R. Williams and coworkers.In their approach, they utilized the Sakurai aiiyiation to introduce the C7 hydroxyl group and the homoallylic side chain. The transformation was effected by BF3-OEt2 at -78 °C to provide the homoallylic alcohol as a 2 1 mixture of diastereomers. The desired alcohol proved to be the major diastereomer, as it resulted from the Felkin-Ahn controlled addition of the allylsilane to the aldehyde. The minor diastereomer was converted into the desired stereoisomer via a Mitsunobu reaction. 

---