1.5- remote asymmetric induction

Remote asymmetric induction using chiral sulfoxides, derivatives of furan, thiophene, and pyrrole 98YGK798. 

Substrate-induced diastereoselection is the most common principle in alkylations of enolates derived from ketones. There are numerous successful applications reported in the literature (for extensive reviews, see refs 1, 3, and 79). The following account does not cover this extensive field with all its applications in detail, but rather presents representative examples which provide a general overview of the different synthetic methods available for alkylations of ketone enolates of various structural types, as well as demonstrating that remote asymmetric induction can be efficient and predictable. 

Stereoselective cyclic hydroboration. The hydroboration of l,4 and 1,5-dienes with thexylborane generally results in boracycles.2 If the intial hydroboration produces an asymmetric center, the second intramolecular hydroboration can be effected with remote asymmetric induction. Thus hydroboration of the diene 1 with thexylborane (1.25 equivalent) followed by oxidation results in a 6 1 mixture of the diastereomers 2 and. 3. An even higher induction is obtained in the case of the 1,4-... 

Synthesis of 12- and 13-membered sulfur-containing lactones by homolytic macrocyclization of mercaptoacetic esters and alkynes has been investigated [95S307]. Reaction of the mercaptoester 245 with alkynes using triethyl borane radical initiation gave the macrolactones 247 and 248 in low yield [95TL2293], Remote asymmetric induction is observed during the cyclization. 

A completely different approach was pursued by Fuji and coworkers [14]. The enantiomeri-cally pure pyridine derivative 18 was prepared, the rationale being that the reduced steric hindrance in the proximity of the nitrogen nucleus should result in efficient catalytic turnover and that chiral recognition might be possible by remote asymmetric induction in a process similar to the induced fit mechanism in enzymes. When 18 was reacted with racemic 19b and isobutyric anhydride (l/ ,25)-19b was recovered with ee = 81% (71% conversion, 5 = 4.5,... 

Arai, Y. Remote Asymmetric Induction Using Chiral (p-Tolylsulfinyl)-Furyl, -Thienyl, and -Pyrrolyl Carbonyl Compounds, Rev. Heteroat. Chem. 1999, 21, 65-91. 

Alkoxy-substituted allylstannanes are transmetalated on treatment with Sn(IV) halides to give allyltin trihalides which react with aldehydes with effective remote asymmetric induction [62]. For example, the 5-benzyloxy-4-methylpent-2-enylstan-nane gives predominantly the 1,5-anti products with useful stereoselectivity (Eq. 37) [62b]. Allylstannanes and 5-benzyloxy-4-methylpent-2-enylsilanes also react with aldehydes with modest levels of 1,5-induction after treatment with SnCU. Trans-metallation to give intermediate allyltin trihalides might be involved (Eq. 38) [63]. 

In an example of remote asymmetric induction, chiral oxazoline (51) undergoes Grignard additions with moderate to good selectivity. The major product formed (52) results fiom coordination of the reagent to the oxazoline moiety, followed by nucleophilic attack fiom the bottom, as shown in Figure 12, The phenyl substituent of the oxazoline effectively prevents addition fiom the top face of the molecule. Systems such as (51) have been used to synthesize opticaUy active i thalides (54), as shown in Scheme 2. Typical optical purities of the isolated aromatic products range from 46-80%. Table 13 lists some of these results. 

Nucleophilic additions to cyclic carbonyl compounds differ greatly from those of acyclic systems. In acyclic systems, only the configuration at an adjacent (1,2-asymmetric induction) or nea y center (remote asymmetric induction) is usually considered in predicting the outcome of nucleophilic attack. In cyclic systems, the conformation of the entire molecule (which is in part determined by the individual substituents) must be considered when predicting the mode of nucleophilic attack. Furthermore, a number of other factors such as torsional and electronic effects also play a role in the stereochemical course of additions to cyclic substrates. The relative importance of all of these effects (as well as others) has been the subject of considerable debate in the literature, and has not as yet been adequately resolved. ... 

Thomas has extended the application of remote asymmetric induction to include conjugated imines (Scheme 5.2.50). ° For example, the formation of the 1,5-anP-product 224 demonstrates a matched facial... 

Fig. 29. Remote asymmetric induction in the hydrogenation of unsaturated carboxylic acids...

Remote asymmetric induction in palladium-catalyzed oxidative cyclizations of this type can be achieved with chiral 2,6-heptadienoates89. 

Asymmetric carbonyl-ene reaction with l.2 The reaction of racemic allylic alcohols (2) with methyl glyoxalatc catalyzed by (R)-l can proceed with remote asymmetric-induction, which suggests that (R)-I can discriminate between the two cne components. 

Cyanohydrins and ethers. Tetracyanoethylene has been introduced as a new catalyst for the carbonyl derivatization. KCN-Znl2 is used to achieve syn-selective derivatization of /3-hydroxy ketones. Exchange of one alkoxy group of an acetal in a TMSOTf-catalyzed process is subject to remote asymmetric induction. The monoadduct of benzoquinones can be reduced by Sml2 to give p-hydroxybenzonitriies. ... 

Dioxolanes derived from a,P y,5-dienals can react with organocopper reagents at both the a- and y-position. Interestingly, chiral dioxolanes of such a substitution pattern give optically active products," due to remote asymmetric induction. 

The same group later reported an efficient route to (—)-galanthamine (75) by a variation of the method whereby remote asymmetric induction was used (216) as well as the total syntheses of siculine, oxocrinine, epicrinine, and buflavine (217). 

A Connection Between Site-Selective Catalysis in Natural Products and Remote Asymmetric Induction... 

Lewis CA, Gustafson JL, Chiu A, Balsells J, Pollard D, Murry J, Reamer RA, Hansen KB, Miller SJ (2008) A case of remote asymmetric induction in the peptide-catalyzed desymmetrization of a bis(phenol). J Am Chem Soc 130 16358-16455... 

Rakotoarisoa, H., Perez, R. G., Mangeney, P. and Alexakis, A. 1996. Remote asymmetric induction. New mechanistic insights concerning the S and S " substitution in organo-copper chemistry. Organometallics 15 1957-1959. 

Stabilized carbanions (acetoacetates, malonates, Meldrum acid, nitroderivatives, and the like) are efficiently aUylated by allylic carbonates under Pd catalysis without added base (Scheme 1). Apart from the cases reported up to 1987 (vide supra), many references witness the possibilities of this type of reaction. " Attention has been paid to asymmetric versions (see Sect Y2.4), " " to several stereochemical and mechanistic aspects, and to remote asymmetric induction " (Scheme 33). New O- to C-rearrange-ments similar to those of Scheme 5 have been published. " Cyanide should be considered also as stabilized C-nucleophile despite its overall inversion stereochemical behavior " (Scheme 10 and Table 1). 

Asymmetric substitution sodium salt Synthesis of mesembrane and mesembrine Synthesis of amaryllidaceae alkaloids Remote asymmetric induction... 

Phenols are more acidic than alcohols and therefore successful Pd-catalyzed allyla-tion of phenols with allylic carbonates is common (Table 3). The situation with alcohols is different since the acidity of the pronucleophile alcohol is similar to the acidity of methanol or ethanol. However, good intramolecular versions have been reported in syntheses of vinyltetrahydrofurans and of linalyl oxides. The use of carbonates of alkyl allyl alcohols in which the alkyl part is coherent with the pronucleophile is particularly successful, as shown in the remote asymmetric induction of Scheme 33. 

A review of remote asymmetric induction using chiral sulfoxides includes a section on reductions of sulfinyl ketones. Recent methods for the stereoselective reduction of... 

Remote asymmetric induction in Michael additions of allylic sulfones to a, -unsaturated esters has been reported (161). ... 

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