Asymmetric Fluoroorganic Chemistry. Synthesis, Applications, and Future Directions

307 Pages·2000·35.75 MB·English

by  P. V. Ramachandran (Eds.)

ACS SYMPOSIUM SERIES 746
Asymmetric Fluoroorganic
Chemistry
Synthesis, Applications,
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0 and Future Directions
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American Chemical Society, Washington, DC
American Chemical Society
Library
1155 16th St., N.W.
In Asymmetric Fluoroorganic Chemistry; Ramachandran, P.;
Washington, D.C. 20036
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
QD 305 .H15A89 2000 c.1
Library of Congress Cataloging-in-Publication Data
Asymmetric fluoroorganic che Asymmetric fluoroorganic
Ramachandran, editor. chemistry : synthesis,
p. cm.—(ACS symposium series ; 746)
Includes bibliographical references and index.
ISBN 0-8412-3639-9
1. Organofluorine compounds—Congresses. 2. Asymmetric synthesis—
Congresses.
I. Ramachandran, P.V. 1954- . II. Series
QD305.H15 A89 1999
547'.02—dc21 99-48380
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In Asymmetric FluoWrooarsghaninicg Ctohenm, istDry.C; .R am20a0ch3a6n dran, P.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
Advisory Board
ACS Symposium Series
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ChemEdit Company AT&T Bell Laboratories
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In Asymmetric Fluoroorganic Chemistry; Ramachandran, P.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
Foreword
JLHE ACS SYMPOSIUM SERIES was first published in 1974 to provide
a mechanism for publishing symposia quickly in book form. The pur
pose of the series is to publish timely, comprehensive books devel
oped from ACS sponsored symposia based on current scientific re
search. Occasionally, books are developed from symposia sponsored
by other organizations when the topic is of keen interest to the chem
1
0 istry audience.
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6.f Before agreeing to publish a book, the proposed table of contents
74 is reviewed for appropriate and comprehensive coverage and for in
0
0- terest to the audience. Some papers may be excluded in order to better
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2 focus the book; others may be added to provide comprehensiveness.
k-
1/b When appropriate, overview or introductory chapters are added.
2
0 Drafts of chapters are peer-reviewed prior to final acceptance or re
1
10. jection, and manuscripts are prepared in camera-ready format.
oi: As a rule, only original research papers and original review pa
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g 99 | pers are included in the volumes. Verbatim reproductions of previ
or19 ously published papers are not accepted.
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In Asymmetric Fluoroorganic Chemistry; Ramachandran, P.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
Preface
Fluoroorganic chemistry, a very important area of research, has attracted agricul
tural, materials, medicinal, and organic chemists alike. The recent flux of activities
is well documented by several monographs and special issues of journals dedicated
to this area. Due to the importance of enantiomerically pure pharmaceuticals,
asymmetric organic synthesis has attracted the attention of organic and medicinal
1
0 chemists alike. A combination of fluoroorganic and asymmetric synthesis has
0
6.pr very great potential. This idea led to a symposium dedicated to the topic of
4
7 Asymmetric Synthesis of Fluoroorganic Compounds that was held during the
0
00- 216th National Meeting of the American Chemical Society (ACS) in Boston,
0
k-2 Massachusettes, August 23 and 24, 1998. The symposium, sponsored by the
1/b ACS Divisions of Fluorine Chemistry and Organic Chemistry, was well received
2
0 by organic chemists from both industry and academia and acted as a catalyst for
1
10. this book.
doi: This volume contains twenty chapters by leading fluoroorganic chemists world
9 | wide who participated in the symposium. The book is organized into sections
org 199 based on the symposium. One of the pioneers of asymmetric fluoroorganic chemis
pubs.acs.mber 29, tcroym, pRooubnedrst oFfi lbleiro mwerodtiec atlh ien telereasdt , cwhahpictehr isd ifsocluloswsiendg bfylu cohrianpet-ecrosn dtaiisnciunsgs incgh irrea l
012 | http://Date: Dece cpaogoneuntnatdi-sn aininngd m tsaaurtgbeesrtti ramalstoe l-cechcoeunmlterisos,tl rlbyeid,o oaagrgsryoamcnhimce mseytirnsitcthr yes,sy inast,n hdae ssypismh,a mrthmeeta rciscyy .nf ltuhoersoiso rogfa nfilcu ocroinme -
August 7, 2Publication gacaaTndihcei smc bhiaoe omakni,sd tw ryihn idcishu sidtnritsyec.n uTdssehediss ftvhooer lucomurgrera encniatc n,s tmbaeta et aeodrfia atplhstee, daa rntf doi rn m aae sgydmricamidnueaatlr teicc h cefomluuiorssrteos oiirnn
fluoroorganic chemistry.
Acknowledgments
I acknowledge all of the speakers who participated in the symposium, especially
those who contributed to this volume. I thank Herbert C. Brown for his support
and advice throughout the organization of the symposium and the production of
this book. I thank the ACS Divisions of Fluorine Chemistry and Organic Chemis
try for sponsoring the symposium. Financial support to the symposium by the
ACS Corporate Associates and ACS Petroleum Research Fund are gratefully
ix
In Asymmetric Fluoroorganic Chemistry; Ramachandran, P.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
acknowledged. Financial support from the following companies also contributed
to the success of the symposium: Dow Agrosciences, Monsanto Company, Aldrich
Chemical Company, Inc., Eastman Kodak Company, Schering-Plough, Merck
Research Laboratories, Central Glass International Inc. (Japan), Daikin Indus
tries (Japan), Kanto Denka Kogyo Company (Japan), and Asahi Glass Company
(Japan). I acknowledge the help provided by Venkat Ram Reddy during the
editing process of the book. Last, but not least, I thank the ACS Books Depart
ment Staff, particularly Anne Wilson and Kelly Dennis, for their remarkable
efforts in the production of this book.
P. V. RAMACHANDRAN
Department of Chemistry
Purdue University
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0 West Lafayette, IN 47907-1393
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In Asymmetric Fluoroorganic Chemistry; Ramachandran, P.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
Chapter 1
Fluorine-Containing Chiral Compounds
of Biomedical Interest
Robert Filler
Department of Biological, Chemical, and Physical Sciences,
Illinois Institute of Technology, Chicago, IL 60616-3793
1
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4 In recent years, there has been a plethora of publications on asymmetric
7
0-0 syntheses and enzymic methods leading to fluorine-containing chiral
0
0 compounds. This review, based on a detailed survey of recent literature,
2
k- focuses on compounds of interest in bio-and medicinal chemistry, e.g., amino
b
21/ acids, anticancer agents, sugars, nucleosides, central nervous system agents,
0
0.1 and anesthetics. Methods involving asymmetric aldol reactions, asymmetric
oi: 1 alkylation, enantioselective fluorinating agents, and enzymically controlled
d reactions are presented. Bioactive fluorine-containing compounds have been
pubs.acs.org mber 29, 1999 | kaa1dnn9vdo5a w0nstnch, eeissn i cnwalcuneedt hiitcnahavgen e ct 1hew9eri 3 tfn0alesug soeasrnenotdds tde51ur-9orfi4linud0goss r,,t o hibuneurh atea cnltiashlu,te ii onhrngee m arfnaoalerrdtskyetah dybe etliaetchr ssed,. e svsueuclbohsp eamqsu ehennatslto othrfaa ptnhiede,
012 | http://Date: Dece abpepenro apcDhareutsri cintuogl atcrhhleyi r appla rsoctno domeupcnoacdueend,d stih nae nremd heaadssiyc mbinemaelne tracihnce imsnycinsrtethraeyss,e edsw . ehmeTrpehh iasa sif so scopunes c nihfeaiwcs
August 7, 2 Publication mcesiongemantnhiptfoiiaodcramse ndetf or wrro oitltrheh e id tnhisa yetshn teterhraseeceose immasd eavortaef n. cochfetiserO.na rl A gbeanxin oehoaaifcblrultiiitoevsrr ei nerfneelpuh cooaonrrtomc oeepdrmog uaptnnhhideacsrs a iczphoeeamduv tpeiaoc urpanlpnadogyste ee( dn1oc )fya.
Since the intent of this paper is to provide an overview which captures the
scope and flavor of these recent developments, it seems quite appropriate to
briefly cite the fascinating range of research studies of the other contributors to
this book.
Bravo and co-workers report asymmetric syntheses of fluoroalkylamino
compounds via chiral sulfoxides and the stereoselective synthesis of β-
fluoroalkyl-β-amino alcohol units using chiral sulfoxides and the Evans aldol
reaction. Bégúe and colleagues discuss the stereoselective and enantioselective
synthesis of trifluoromethyl amino alcohols and fluoroalkyl isoserinates.
Hoffman reports the aysmmetric fluorination of α-aminoketones, while
© 2000 American Chemical Society 1
In Asymmetric Fluoroorganic Chemistry; Ramachandran, P.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
2
Soloshonok describes his continuing studies on a practical asymmetric
methodology for the synthesis of enantiopure fluoro amines and amino acids.
Chemical and biochemical approaches to non-racemic fluorinated
catecholamines and amino acids are explored by Kirk and co-workers. Ramig
discusses recent studies of the chiral fluorinated anesthetics, halothane,
enflurane, isoflurane, and desflurane. Ojima and colleagues report exciting
new results on the synthesis of enantiopure fluorine-containing analogs of
paclitaxel and docetaxel and their use as anticancer agents and as important
biochemical probes. In their studies of natural products containing fluorine,
O'Hagan and Harper trace the biosynthetic origin of fluoroacetate and 4-
fluorothreonine in a Streptomyces bacterium. Iseki reports efficient
asymmetric syntheses of fluorinated aldols and nitro aldols of high
1
0 enantiomeric purity, while Yamazaki discusses the construction of chiral
0
ch aldols with fluorine-containing methyl groups starting from D-glucose.
6.
4 Hamper and co-workers at Monsanto describe the synthesis and herbicidal
7
0
0- activity of enantiomeric lactate derivatives of trifluoromethyl-substituted
0
20 pyrazole herbicides. Resnati and colleagues discuss the resolution of racemic
bk- perfluorocarbon halides via self-assembly involving intermolecular electron
1/
2 donor-acceptor interactions. A variety of reactions leading to fluorine-
0
0.1 containing chiral molecules useful as liquid crystals are reported by Hiyama
1
oi: and co-workers. In the search for new antimicrobial agents bearing the β-
9 | d lactam moiety, Welch and co-workers report the preparation of a chiral 3-
pubs.acs.org mber 29, 199 b(fatlnurudiiocl dryEoicnatl3gizNc e b)t βildoa-lincankdco tniaanemn ab oydm pecurtyiilvctciaalsotltileavypde da)si.cy ttinioAvtnhen e osiamfir sfyp loluoifomr traaio nnnkteee .wft ee anTfteluhu (reofe rr oaiinzmsee t- thfcildeoui nondtrooaonimanecii nnestageyn rltvc rceiebh saol ocfa rtsati hdmaee
012 | http://Date: Dece esoalregmcatenr oocbnaoircrba oenfnef.se ctRd eoarmfi vfalecudho arfinrndoerm aon v αea-rnp tdihn eeB nsretoe wriinnc iarne fvtlhiuereewnec -tpehr eooinfr g aae pmdp elatihcpayptlri ooganrcoshu o pf f oocrnh ittrhhaeel
August 7, 2 Publication pe(f3lnrue)ao pnraatiisrnoayamtmtieoemdnr i ekcte rotiocfe n xeecsane,sso ys(l2.mb )om raasetRytiromeicnam c-ateilotodrrniogcsla i aznlaoilntyficlloublnuoo drroiaenft eio f(ln1u )coo ofrm oaf slpuyaoomludrmneinhdeaystt dreiedcsi na l radenedvdhue yrcdyktie eostno,h n aiegnoshdf.
Using B-chlorodiisocampheylborane, the stereochemical outcomes in reactions
(1) and (3) are apparently influenced by the presence of fluorines in the
molecules. Ramachandran and colleagues review and compare the Morita-
Baylis-Hillman (MBH) reaction and vinylmetalation (aluminum and copper) of
fluorocarbonyls as routes to achiral and chiral fluorinated allyl alcohols. Use
of terpenyl alcohols as chiral auxiliaries in asymmetric MBH and
vinylmetalation reactions is explored. Mikami reports the asymmetric
synthesis of diastereomeric a- or β- CF liquid crystalline (LC) molecules by a
3
carbonyl-ene reaction using fluoral in the presence of a chiral binaphthol-
derived titanium catalyst (BINOL-Ti). These LCs function as conformational
In Asymmetric Fluoroorganic Chemistry; Ramachandran, P.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
3
probes for ferroelectricity. The first example of spontaneous resolution of
racemates in fluid LC phases has been observed with these diastereomers.
Ishii and Mikami describe the first example of asymmetric catalysis (BINOL-
Ti) in the Friedel-Crafts reaction of aryl compounds with fluoral to provide a
practical route to chiral α-trifluoromethylbenzyl alcohols. Highly enantiopure
β-trifïuoroaldols have also been prepared from vinyl ethers via sequential
diastereoselective reactions.
Fluoroamino Acids
Fluorine-substituted amino acids have often been used as probes to follow
biochemical reactions. During the past few years, asymmetric syntheses of
1
0 fluoro α-amino acids have been the subject of intense activity. Thus,
0
h
c Soloshonok and co-workers (2) reported highly diastereoselective asymmetric
6.
74 aldol reactions between prochiral trifluoromethyl ketones and the Ni (II)-
0
0- complex of the monochiral Schiff base of glycine (Figure 1) and established
0
0
2 reaction conditions for preparative syntheses of diastereo- and
k-
b enantiomerically enriched trifluoromethyl-substituted serines. Sting and
1/
02 Seebach (3) converted enantiopure (S) - 4,4,4 - trifluoro - 3 - hydroxybutanoic
1
0. acid in several steps to dioxanones, whose enolates were stereoselectively
1
oi: aminated with di- tert - butyl azodicarboxylate, DBAD. Acidic ring-opening
d
9 | and removal of the N-Boc groups provided the corresponding α-hydrazino -β -
org 199 hydroxyesters which, on hydrogenolysis, gave the threonine analog (2R, 3S) - 2
acs.29, - amino - 4,4,4 - trifluoro - 3- hydroxybutanoate methyl ester (1) (Figure 2).
pubs.mber Pthrreevoinoiunse saynndt haeltlioct harnedo neinnez ybmy aotitch ear pipnrvoeascthigeast otros atrrief ludoisrcoumsseetdh yiln atnhaislo gpsa poefr
012 | http://Date: Dece t(pr3rie)f.lp uaEorrenodap nrtoibopyma neortiihcce a allcyia des ynemrsitcmehreset drw i3cit ,h3 ,r3ae- d ctuhricifrtlaiuolo nor oxaaolzafa nbion2re-o ((lNuidp-ia ntroey l6ciam3t%ainl yeose)t ) (-he qasu3 a,b3tei,oe3nn-
August 7, 2 Publication t41r,i)4f(l,44u)-o. roImnt reaitf hlnuyoolvarteoilob nua pta(pFnrioogiaucc rhe, 3aa)n c(i 5de) n. anInwti otahsme ekriescyya nlslttyhe peps,u iGzreea drd neerri'vvsai aati lvdeen houyfcd l2ee -oa(2pm)h ii(nl6oi)c-,
an oxazolidine derived from L-serine, reacted with the Ruppert-Prakash
reagent, TMS-CF (a trifluoromethide equivalent) (7) and tetrabutylammonium
3
fluoride. (S) - 5,5,5,5',5',5'- Hexafluoroleucine (3) (88% ee) was prepared in
18% overall yield from hexafluoroacetone and ethyl bromopyruvate in seven
steps (8). The highly enantioselective reduction of the keto carbonyl group of
4 to the hydroxyester 5 either by baker's yeast and sucrose (91% ee) or by
catecholborane and an oxazaborolidine catalyst (99% ee) was the pivotal
reaction of the sequence. These workers (9) also prepared (-)-(R)- 4,4,4,4',4',4f
-hexafluorovaline (6) (98% ee). The key step was the separation of the
tosylate salts of the diastereomers formed by anti-Michael addition of (+)-(R)-
In Asymmetric Fluoroorganic Chemistry; Ramachandran, P.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.
4
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1
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4
7
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0- 90-98% de
0
0
2 R= CH (a), CH (b), CH (c), CH (d), (CH)Ph (e), C=C-Ph (I)
k- 3 4 g 7 I5 8 17 23
b
1/ Figure 1. Highly diastereoselective asymmetric aldol reactions of chiral Ni(II)-
2
10 complex of glycine with CF3COR (2).
0.
1
oi:
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9 |
org 199
acs.29,
pubs.mber
August 7, 2012 | http:// Publication Date: Dece HCI, MeOH 1) H2, Pt02, MeOH 71-97% dRi aB=s toHeer,e HMomNe,e' rBicu , rPahti o > 98:2
F j C ' Y ^ O Me
2) NaHC0
3
11-47% NH2
CIH3N
1
Figure 2. Synthesis of (2R, 3S)-2-amino-3-trifluoromethyl-3-hydroxy alkanoic acid
derivatives (3).
H.Ph
BH- ζ I Ο
Ç0Et Ο X —B CO,Et
2
FaC^Np-MeOQ^ FC^NHp-Me0CH <1}
3 6 4
THF
93% 9 3% ee
(R)
In Asymmetric Fluoroorganic Chemistry; Ramachandran, P.;
ACS Symposium Series; American Chemical Society: Washington, DC, 1999.