Chiral homoallylic alcohol

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. 

Mikami reported a highly enantioselective carbonyl-ene reaction where a chiral titanium complex 11 prepared from enantiomerically pure binaphthol (BINOL) and Ti(0-i-Pr)2Br2 catalyzed a glyoxylate-ene reaction with a-methylstyrene to give chiral homoallyl alcohol 12 with 94.6% ee [22]. In this reaction, a remarkable asymmetric amplification was observed and almost the same enantioselectivity (94.4% ee) was achieved by using chiral catalyst prepared... 

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. 

W. Adam, C. R. Saha-Moller, and K. S. Schmid, Synthesis of 4,6-dideoxyfuranoses through the regioselective and diastereoselective oxyfunctionalization of a dimethylphenylsilyl-substituted chiral homoallylic alcohol, J. Org. Chem., 66 (2001) 7365-7371. 

Chiral pyrrolidinylmethylallylsilanes have been shown to be good reagents that transfer their allyl group to aldehydes to synthesize chiral homoallylic alcohols.273... 

Chiral homoallylic alcohols and amines were prepared by using a four-component condensation reaction based on a zinc homologation followed by a trapping with an aldehyde or an imine.301 A regio- and stereospecific carbocupration reaction on alkynyl sulfoxide provides the corresponding metallated /3,/3-dialkylated a,/ -ethylenic sufoxide 98. Addition of aldehydes or imines, followed by addition of the bis(iodomethyl)zinc carbenoid, provides adducts 99 in good overall yield and with very high diastereoselectivity (Scheme 36). 

Asymmetric allylation is performed by chiral allylating reagents. The chiral allyltin generated in situ from benzodio-stannole [Sn(02C6H4)], allyl halide, chiral dialkyl tartrates and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) reacts with aromatic aldehydes in the presence of copper salts to afford the chiral homoallyl alcohols (Equation (50)).164... 

Chiral homoallylic alcohols. The borane 1 reacts with aldehydes in ether at - 78° to furnish, after oxidation, chiral secondary homoallylic alcohols (2) with enantiomeric excesses of 83-96%. The addition occurs in all six cases examined in the same stereochemical sense. 

Chiral homoallylic alcohols. The chiral acetals 2 formed from an aldehyde and 1. undergo titanium-catalyzed coupling with allyltrimcthylsilane with marked stereoselectivity. Highest sterco.selectivity is usually obtained with the mixed catalyst TiClj-Ti(0-/-Pr)j (6 5). Cleavage of the chiral auxiliary, effected by oxidation to the ketone followed by -elimination, provides optically active alcohols (4) with —95% ee (equation I). ... 

Chiral homoallylic alcohols, The glycol 1 has been used as the chiral matrbt in an enantioselective synthesis of homoallylic alcohols (4) from aldehydes and allyl-boranes (equation I). 

Prochiral a-(acylamino)acrylic acids or esters are hydrogenated under an initial hydrogen pressure of 3-4 atm to give the protected amino acids in up to 100% ee (eq 16). The BINAP-Rh catalyst was used for highly diastereoselective hydrogenation of a chiral homoallylic alcohol to give a fragment of the ionophore... 

Methyl chloroacetate reacts with the anion of (7 )-methyl p-tolyl sulfoxide to give the corresponding 8-chloro-p-keto sulfoxide (eq 10), which can be easily transformed into the corresponding 3-hydroxy sulfoxide which gives, in presence of a base, the optically active a-sulfinyl epoxides. As illustrated here, a-sulfinyl epoxides can be opened by cuprates, leading to chiral homoallylic alcohols. ... 

In the presence of a scandium catalyst, chiral allylic boranes open epoxides at the less substituted position to generate chiral, homoallylic alcohols. 

From the range of synthetic applications of Brown s pinene-derived allyl- and crotylborane reagents illustrated in these selected examples, it is clear that they are excellent reagents for the synthesis of chiral homoallylic alcohols from chiral and achiral aldehydes alike. That so many researchers have applied these reagents in their research also attests to the great utility of these reagents in organic synthesis. 

Allylation of ketones is a fundamental and important transformation, and therefore, efficient catalysts promoting addition of allylstannanes to ketones have been investigated [89]. Enantioselective allylation of ketones is a very challenging topic. It has been disclosed that asymmetric allylation of ketones with allylstannanes was promoted by addition of BINOL/TiCl2(OiPr)2 catalyst [90] or by premixing of BINOL with tetraallyltin [91]. In these reactions, however, enantioselectivity was not sufficient for practical purposes (acetophenone <65% ee). It was recently discovered that acetophenone was allylated by a mixture of tetraallyltin and an alkyl-triallyltin in the presence of monothiobinaphthol to furnish the desired chiral homoallyl alcohol with high enantioselectivity (Scheme 12.35) [92]. 

Iseki et al. later improved the catalytic process and showed that chiral phos-phoramides 15,16, and 17, prepared from (S)-proHne, are suitable to catalyze the asymmetric allylation of aromatic aldehydes to give chiral homoallylic alcohols 34 with up to 88% ee (Scheme 13) [36,37]. The same group has also developed a chiral formamide 18 as a chiral Lewis base catalyst [38]. This catalyst is convenient for the allylation of aUphatic aldehydes with high enantioselectivity. A typical aromatic aldehyde, benzaldehyde, gives a low enantiomeric excess (Scheme 13). 

B-Allylbis(isocarany )boranes (1) can deliver the allyl group to carbonyl substrates to give chiral homoallylic alcohols. 

The high selectivity of olefin metathesis with (2a) was key in the formation of diverse nonracemic vinyl cyclopropanes from chiral homoallylic alcohols and allyl chlorodimethylsilane in three steps, or allyl trimethylsilane in two steps, giving diastereomerically pure cis or trans... 

Brown et al. reported the stereoselective preparation of spiro-ketals via an extension of the above protocol involving the stepwise hydroboration of protected chiral homoallylic alcohols with IpcBCU (eq 19). ... 

Luft JAR, Meleson K, Houk KH. Transition structures of diastereoselective 1,3-dipolar cycloadditions of nitrile oxides to chiral homoallylic alcohols. Org. Lett. 2007 9 555-558. 

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