Planar−Chiral Heterocycles as Ligands in Metal-Catalyzed Processes:  Enantioselective Addition of Organozinc Reagents to Aldehydes

Dosa, Peter I.; Ruble, J. Craig; Fu, GC

doi:10.1021/jo962156g

Cited by 207 publications

(66 citation statements)

References 8 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Yields in the phenylation reaction with DAIB ranged from 53% to 91%. In contrast to the phenylation of ketones, several highly enantioselective catalysts have been developed for the asymmetric addition of phenyl groups to aldehydes (14)(15)(16)(17)(18)(19)(20).…”

mentioning

confidence: 99%

Catalytic asymmetric addition of diphenylzinc to cyclic α,β-unsaturated ketones

García

Walsh

2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

We have examined the use of our bis(sulfonamide) diol ligand (1) in the asymmetric addition of phenyl groups to cyclic ␣,␤-unsaturated ketones. Good to excellent enantioselectivities have been obtained with cyclic enones bearing alkyl substituents in the 2 position (71-97% enantiomeric excess). Furthermore, excellent enantioselectivities have been observed in the asymmetric phenylation of cyclic enones with 2-iodo and 2-bromo substituents. The results of this study broaden the scope of the asymmetric additions to ketones promoted by the titanium catalyst derived from ligand 1.alkylation ͉ tertiary alcohols ͉ zinc ͉ titanium ͉ asymmetric catalysis W e recently developed a highly enantioselective titanium catalyst based on the bis(sulfonamide) diol ligand 1 (Fig. 1) for the asymmetric addition of alkylzinc reagents to ketones (Eq. 1; ref. 1). When cyclic ␣,␤-unsaturated ketones were used as substrates, we found that the asymmetric addition reaction could be coupled with a diastereoselective epoxidation by using molecular oxygen as the oxidant to provide a one-pot synthesis of epoxy alcohols with high enantio-and diastereoselectivity (Eq. 2; ref. 2). These studies provide a solution to a long-standing problem in synthetic organic chemistry: the catalytic synthesis of tertiary alcohols from ketones with high enantioselectivity. Unlike related additions of dialkylzinc reagents to aldehyde substrates, which are promoted by hundreds of catalysts (3, 4), only a few systems will catalyze alkyl additions to ketones (1, 2, 5-8), and most of them use high catalyst loadings and long reaction times (6-8).The successful use of ligand 1 in the alkyl additions to ketones led our group (9) and Yus and coworkers (10) to examine the enantioselective phenylation of acyclic ketones with ZnPh 2 . The only previous results in the catalytic asymmetric phenylation of ketones were reported by Dosa and Fu in 1998 (11). In this pioneering work, these authors used Noyori's amino alcohol ligand, (ϩ)-3-exo-(dimethylamino)isoborneol [(ϩ)-DAIB] (12, 13), and diphenylzinc (3.5 eq). Initially, the reaction gave low yields and moderate enantioselectivities. It was found, however, that addition of 1.5 eq of methanol to the diphenylzinc resulted in formation of a mixed alkoxy phenyl zinc reagent that led to increased yields and enantioselectivities (Eq. 3) (11). Under these conditions, excellent enantioselectivities were obtained with substituted propiophenones [86-91% enantiomeric excess (ee)], and acetophenone derivatives afforded enantioselectivities as high as 80%. In the case of cyclohexyl methyl ketone and 3-methyl-2-butanone, the reaction proceeded with 75% and 60% enantioselectivities, respectively. Yields in the phenylation reaction with DAIB ranged from 53% to 91%. In contrast to the phenylation of ketones, several highly enantioselective catalysts have been developed for the asymmetric addition of phenyl groups to aldehydes (14-20).In our initial study on the addition of diphenylzinc to acyclic ketones with ligand 1, we found that enantio...

show abstract

mentioning

confidence: 99%

Catalytic asymmetric addition of diphenylzinc to cyclic α,β-unsaturated ketones

García

Walsh

2004

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Alcohols such as methanol, 2-propanol, tert-butyl alcohol, tetrahydrofuranol and phenol are deprotonated by zinc reagents and lead to the formation of alkoxyaryl-zinc species, which have previously been shown to add to aldehydes. [14] Among the tested alcohols, 2-propanol gave the best results. Figure 3 demonstrates that the amount of added alcohol is decisive for the outcome of the reaction.…”

Section: Resultsmentioning

confidence: 97%

A High-Throughput Screening Approach for the Determination of Additive Effects in Organozinc Addition Reactions to Aldehydes

Rudolph

Lormann

Bolm

et al. 2005

Advanced Synthesis & Catalysis

View full text Add to dashboard Cite

The effects of additives in phenylzinc addition reactions to an aldehyde have been studied using an automated high-throughput screening approach. With 2-bromobenzaldehyde as test substrate and N,N-dibutylnorephedrine (dbne) as chiral ligand, an improvement of 20% ee over the catalyzed reaction in the absence of the additive was observed. The described results enable a novel access towards chiral diarylmethanols using commercially available substrates, reagents and ligands as well as fast, automated techniques.

show abstract

“…1 H NMR spectra at 400 MHz and 13 C NMR spectra at 100.70 MHz were recorded on a 400 MHz NMR spectrometer.…”

Section: Methodsmentioning

confidence: 99%

“…The first asymmetric phenyl addition reaction was reported by Seebach and coworkers, employing the titanium catalyst of TADDOLate ligand and the highly reactive PhTi(O-iPr) 3 reagent. 12 After the work of direct ZnPh 2 additions by Fu et al, 13 various zinc catalytic systems employing ZnPh 2 , [14][15][16][17] phenylzinc reagents [18][19][20][21] from reactions of dialkylzinc compounds and ZnPh 2 , or arylzinc compounds 9,[22][23][24][25][26] have been reported to afford diarylmethanols in high enantioselectivities. Though arylzinc reagents are not available commercially, they can be prepared in situ from reactions of excess ZnEt 2 with arylboronic acid at elevated temperatures for 12 h 22 or from reactions of aryllithiums with ZnCl 2 and n-butyllithium.…”

Section: Introductionmentioning

confidence: 99%

1,3‐bis[N‐sulfonyl‐(1R,2S)‐1,3‐diphenyl‐2‐aminopropanol]benzene: An excellent ligand for titanium‐catalyzed asymmetric AlPh₃(THF) additions to aldehydes

et al. 2008

View full text Add to dashboard Cite

Asymmetric AlPh(3) (THF) additions to a wide variety of aldehydes catalyzed by a titanium catalyst of 20 mol % 1,3-bis[N-sulfonyl-(1R,2S)-1,3-diphenyl-2-aminopropanol]benzene (1) are reported. The catalytic system works excellently for aromatic aldehydes bearing either an electron-donating or an electron-withdrawing substituent on the aromatic ring to afford secondary diaryl alcohols in excellent isolated yields of >or=95% and excellent enantioselectivities of >or=94% ee. The phenyl addition to cinnamaldehyde or 2-furylaldehyde gave corresponding secondary alcohols in 85% and 95% ee, respectively. For aliphatic aldehydes, increasing enantioselectivities of the addition products in terms of increasing steric sizes of aldehydes are observed, and this trend goes from the linear 1-pentanal (87% ee), the secondary cyclohexylaldehyde (95% ee) or the 2-methylpropanal (97% ee), to the tertiary 2,2-dimethylpropanal (99% ee).

show abstract

Planar−Chiral Heterocycles as Ligands in Metal-Catalyzed Processes: Enantioselective Addition of Organozinc Reagents to Aldehydes

Cited by 207 publications

References 8 publications

Catalytic asymmetric addition of diphenylzinc to cyclic α,β-unsaturated ketones

Catalytic asymmetric addition of diphenylzinc to cyclic α,β-unsaturated ketones

A High-Throughput Screening Approach for the Determination of Additive Effects in Organozinc Addition Reactions to Aldehydes

1,3‐bis[N‐sulfonyl‐(1R,2S)‐1,3‐diphenyl‐2‐aminopropanol]benzene: An excellent ligand for titanium‐catalyzed asymmetric AlPh₃(THF) additions to aldehydes

Contact Info

Product

Resources

About

Planar−Chiral Heterocycles as Ligands in Metal-Catalyzed Processes: Enantioselective Addition of Organozinc Reagents to Aldehydes

Cited by 207 publications

References 8 publications

Catalytic asymmetric addition of diphenylzinc to cyclic α,β-unsaturated ketones

Catalytic asymmetric addition of diphenylzinc to cyclic α,β-unsaturated ketones

A High-Throughput Screening Approach for the Determination of Additive Effects in Organozinc Addition Reactions to Aldehydes

1,3‐bis[N‐sulfonyl‐(1R,2S)‐1,3‐diphenyl‐2‐aminopropanol]benzene: An excellent ligand for titanium‐catalyzed asymmetric AlPh3(THF) additions to aldehydes

Contact Info

Product

Resources

About

1,3‐bis[N‐sulfonyl‐(1R,2S)‐1,3‐diphenyl‐2‐aminopropanol]benzene: An excellent ligand for titanium‐catalyzed asymmetric AlPh₃(THF) additions to aldehydes