This article was downloaded by: [Central Michigan University]On: 04 November 2014, At: 07:06Publisher: Taylor & FrancisInforma Ltd Registered in England and Wales Registered Number:1072954 Registered office: Mortimer House, 37-41 Mortimer Street,London W1T 3JH, UK

Synthetic Communications:An International Journalfor Rapid Communication ofSynthetic Organic ChemistryPublication details, including instructions forauthors and subscription information:http://www.tandfonline.com/loi/lsyc20

Asymmetric Reduction ofChiral Titanates of α-KetoAromatic Acids with LithiumDialkyl AmidesDuan Xin-Fang a & Yin Cheng-Lie aa Department of Chemistry , Beijing NormalUniversity , Beijing, 100875, ChinaPublished online: 22 Aug 2006.

To cite this article: Duan Xin-Fang & Yin Cheng-Lie (1997) Asymmetric Reductionof Chiral Titanates of α-Keto Aromatic Acids with Lithium Dialkyl Amides,Synthetic Communications: An International Journal for Rapid Communication ofSynthetic Organic Chemistry, 27:5, 825-828, DOI: 10.1080/00397919708004202

To link to this article: http://dx.doi.org/10.1080/00397919708004202

PLEASE SCROLL DOWN FOR ARTICLE

Taylor & Francis makes every effort to ensure the accuracy of allthe information (the “Content”) contained in the publications on ourplatform. However, Taylor & Francis, our agents, and our licensorsmake no representations or warranties whatsoever as to the accuracy,completeness, or suitability for any purpose of the Content. Any opinionsand views expressed in this publication are the opinions and views ofthe authors, and are not the views of or endorsed by Taylor & Francis.The accuracy of the Content should not be relied upon and should beindependently verified with primary sources of information. Taylor and

Francis shall not be liable for any losses, actions, claims, proceedings,demands, costs, expenses, damages, and other liabilities whatsoeveror howsoever caused arising directly or indirectly in connection with, inrelation to or arising out of the use of the Content.

This article may be used for research, teaching, and private studypurposes. Any substantial or systematic reproduction, redistribution,reselling, loan, sub-licensing, systematic supply, or distribution in anyform to anyone is expressly forbidden. Terms & Conditions of accessand use can be found at http://www.tandfonline.com/page/terms-and-conditions

Dow

nloa

ded

by [

Cen

tral

Mic

higa

n U

nive

rsity

] at

07:

06 0

4 N

ovem

ber

2014

SYNTHETIC COMMUNICATIONS, 27(5), 825-828 (1997)

ASYMMETRIC REDUCTION OF CHIRAL TITANATES OF a-KETO AROMATIC ACIDS WITH LITHIUM DLALKYL AMIDES

DUAN XIN-FANG YIN CHENGLIE*

Department of Chemistry, Beijing Normal University , Beijing, 100875 , China.

Abstract Asymmetric reduction of titanates of a-keto aromatic acids with chral alcohol ligands by lithium dialkyl amides yielded the acids’ corresponding mandelic acids in 20.1 to 43.3 %ee.

Organotitanium RTi(OR’)3, modified by a variety of chiral ligands, can add to carbonyl

compounds with high enantio~electivity~’~~~~’. Altemativerly, additions of RLi, RMgX, R2Zn to

carbonyl compounds mediated by chiral titanium dcrivatives such as Ti-TADDOLate can also

show high enantioselecti~ity[”~~. In these reactions “ate” complexes form between chiral

titanates and the organic portion of the organometallics due to the Lewis’s acidity of titanates.

Considering these two examples of chiral titanates used to m o d e organometallics we

developed a system involving titanates of a-keto aromatic acids and Li reagentst6’. We

expected to produce enantiomerically enriched a-hydroxyl acids through asymmetric induction

by taking advantage of the above describled two types of modification with chiral titanates in

one reaction: titanates of keto acids can be modified in the same way as RTi(OR)3 by chiral

ligands meanwhile RLi can by the “ate” complex formed with titanates of acidsrwith even

stronger Lewis’s acidity than Ti(OR’)d]. When we reacted titanates of a-keto aromatic acids

825

Copyright 0 1997 by Marcel Dekker, Inc.

Dow

nloa

ded

by [

Cen

tral

Mic

higa

n U

nive

rsity

] at

07:

06 0

4 N

ovem

ber

2014

826 DUAN AND YIN

I a* 2 conlig InIu '%tee yicld('Xt) 2a S +30 27 2 0 7 47 2b S +679X 4 3 3 49 2c S +3G 74 23 4 41

with lithium dialhyl amides. the keto acids were reduced to their corresponding inandelic

acids"'. In view of the encouraging results achieved by organotitanium in asymmetric reactions

and the frequent presence of optically active inandelic acids in iiumerous natural products, we

Ib** c o i ~ g [aJD %ee yield(%)

S +3359 23 0 51

investigated further the asynuiietric reaction bctwcen titanates of a-keto aromatic acids and

lithiuni diallql amides, which in principle may afford enantiomerically enriched mandelic

acids

Modification of the titanates of a-keto aromatic acids with c h i d alcohol ligands was

siniplc: ACter the exchange reactions behveen titaiiates Ti(OR')I and tlie acids, leading to

l'orniation of tlie acids' salts of titanium, chiral alcohols were introduced into the resulted

dcrn atn es tluough further exchange reactions The so-obtauied clural titanates were treated

with lithium dialh34 aiiiides in situ. After quenching by addition of a 3N HC1 solution, the

corrcspoiiding niandelic acids wcre obtained as illustrated below:

11 K*011 - ArCOCOOTi(OR1)3.,(OR*), ArCOCOOlI + Ti(ORI), L ~ C ! O U ~ O ' I ~ ( O R

2a 2h 2L:

We uscd di-0-isopropylidenc-D-inannitol as chiral ligand, and chose 2a; 2b, 2c as

aniidcs to pcrfonn the asyuinietric reduction. The results are listed in Table 1.

Table 1 Results of the Asyimnetric Reduction by Use of h i d e 2a,2b,2c

Titanatc was Ti(0Pr' )?, thc tenipcrat~irc of the reactions was -40 to-SOC The products.

aftcr rccryslallimtion. have the same melting points as the reported(1a 133 - 134'C. l b 104

Dow

nloa

ded

by [

Cen

tral

Mic

higa

n U

nive

rsity

] at

07:

06 0

4 N

ovem

ber

2014

TITANATES OF a-KETO AROMATIC ACIDS 827

R'

- 105%) and their [ a ] ~ were detemiined in an alcoholic(1a)or water (Ib) solution of with

concentrations between 0.1 and OS(gi100mL) .The %ee was calculated by comparing the

determined [ a ] ~ with the reported.

* its reported [aID is f157(c=2.5, ethanol)[81

** its reported [ a ] D is +146(c=2.5, water)[91

Et Pr' But

When the reactions started &om different Ti(OR1)4(R' =Et,Pr',But) the influence of the

ligand OR' of titanates[ArCOCOOTi(DIPM))(OR')] was also investigated. Of the tluee

ligands, the OBu' gave the highest ee as listed in Table 2.

%ee

Table 2 Results of the Asymmetric Reduction of l a with Different Titanates

20.1 20.7 31.4

The configurations of the products was S: the temperature as reported in Table 1

Typical procedure

In a 250-inL four-necked flask, equipped for distillation, with a stirrer in it, 80 mL

toluene was added. 10 inmol titanate in benzene was added by pipette, and then 10 mmol keto

acid. The mixture was heated to remove the exchange-resulted alcohol through azeotropic

distillation. To the residue, 30 mnol monodentate chiral alcohol or 10 mmol bidentate chiral

alcohol dissolved in 100 mL toluene was added for the further exchange reaction. After

another azeotropic distillation; the residue, a pale yellow oily liquid was diluted with 30 mL

toluene, then the mixture was cooled to -40 to -50%. The 10 mmol lithium dialkyl amide

(prepared from 10 5 mnol dialhyl amine in 20 mL ether and 8 3 mL 1 2 M hexane solution of

Bu"Li ) was added. and the temperature maintained for one hour. The mixture was allowed to

warm to room temperature overnight. 30 mL 3N HC1 aqueous solution was added. After

several hours, the organic layer of the mixture was separated ,and the water phase extracted 3

Dow

nloa

ded

by [

Cen

tral

Mic

higa

n U

nive

rsity

] at

07:

06 0

4 N

ovem

ber

2014

828 DUAN AND YIN

times with ether . The combined organic layer was extracted by 10% NaHC03 aqueous

solution and the aqua-base solution was acidified by adding concentrated HCI . After

extracting the acidlfied solution with ether ,the ether was dried over anhydrous MgSO,. The

mandelic acid was afforded after removing the ether. Its value of [ a ] ~ was determined after

recrystallization from benzene with the same melting point as the reported[la: 133 - 134‘C;lb:

I04 - 105’Cl

References

I.Seebach, D.; -xk , A.K.; Imiwinkelried, R.; Roggo, S.; Wonnacott, A. Helv. Chim. Acta

1987,70;954

2.Reetz, M.T.; Kukenhohner, Th.; Weining, P. Tetrahedron Lett. 1986,27,5711

3.Seebach, D.; Beck, A.K.; Imiwinkelried, R.; Roggo, S.; Wonnacott, A. Chem. Ber. 1985,

1 18,3673

4.Takahashi, H.; Kawahata, A.; Niwa, H.; Higashhiyama, K. Chem. Pharm. Bull.

1988,36,803

S.Schmidt, B.; Seebach, D.,Angew. Chem. Inf. Ed Engl., 1991,30,99-10I

6.Duan Xin-Fang; Yin Cheng-Lie, Acta Chimica Sinica, 1995, 53,411-416 [C.A. 1995, 123,

554544

7.Duan Xin-Fang; Yin Cheng-Lie, Journal of Moleclar Science, in press.

8. HeilbronJ.; Bunbury, H.M., “Dictionaly of Organic Compounds”, London: Eyre &

Spottiswoode,l953, Vol. 2: pp781.

9,Heilbron,I.; Bunbury, H.M., ‘‘Dictionaly of Organic Compounds”, London: Eyre &

Spottiswoode, 1953,Vol. 3: pp212,.

(Received i n the USA 16 September 1996)

Dow

nloa

ded

by [

Cen

tral

Mic

higa

n U

nive

rsity

] at

07:

06 0

4 N

ovem

ber

2014