Acros Organics acta N°004

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a Fisher Scientific Worldwide company

4April 1998 Acros Organics journal

for chemists

Acros Organics

acta

Di s co v e r wh a t s n e w a t A cro s Or gan i c s o n ba ck - co v e r !

2-(Trimethylsilyl)thiazoleA Versatile FormylCarbanion Equivalentfor Organic Synthesis 1

2,2-Dimethyl-1,3-dioxan-5-oneA Dihydroxyacetone

Equivalent forAsymmetric Synthesis 5

Camphor DerivativesOxazoline-N-oxidesNew Chiral Auxiliariesfor Asymmetric [2+3]Cycloadditions 9

The Chemistry of thep -Isopropylcalixarenes 13


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Have you already noticed .

Here are some new Acros Organics Info Sheets:

No 25: N,N-Diisopropyl-1-fluoro-2-methylpropenyl-amine, a powerful reagent for fluorination of alcohols under neutral conditions.

No 26: 1,3,4-Triphenyl-4,5-dihydro-1H-1,2,4-triazol-5- ylidene and 5-methoxy-1,3,4-triphenyl-4,5-dihydro-1H-1,2,4-triazolin. The first commer-cially available stable carbene and a versatileprecursor for its preparation and in situ forma-tion.

No 27: R,R- and S,S-bis(2,2-phenylthiomethyl)dihy-dropyrans. One pair in the series of Leyreagents. Efficient protecting and resolvingagents for 1,2- diols.

No 28: Asymmetric Catalysis with chiral dirhodium(II)carboxamidates.

No 29: 2,2-Dimethyl-1,3-dioxan-5-one, a dihydroxy-acetone equivalent for asymmetric synthesis.

No 30: (R)-(-)-2-(2-Isoindolinyl)butan-1-ol, a novel chi-ral -aminoalcohol for asymmetric reduction of prochiral ketones.

No 31: Camphor derivatives oxazoline-N-oxides, newchiral auxiliaries for asymmetric [2+3] cycload-ditions.

No 32: Bis-(2,4,6-trimethylpyridine)iodine(I)hexafluo-rophosphate, a powerful iodinating agent.

No 33: Ethenyl-, ethynyl-, propadienyl- and 1-propy-nyltributylstannanes, useful unsaturated stan-nanes in organic synthesis.

No 34: 2-(Trimethylsilyl)thiazole.

No 35: 1,5-Diazabicyclo[4,3,0]non-5-ene (DBN).

No 36: 2,2-Dimethyl-1,3-dioxan-5-one, a dihydroxy-acetone equivalent for asymmetric synthesis.

No 37: (S,E)-(-)-Methyl-4-(phenylmethoxy)-2-pen-tenoate, a synthetically useful enantiopurebuilding block.

To be continued

Acros Organics is the alternative source for fine chemi-cals in prepack and semi-bulk quantities and is offeringmore than 15,000 organic chemicals for research andindustry. A great many of these products are also avail-able in bulk quantities.

Part of our commitment to our customers is to informthem on recent developments and interesting researchperformed on and with reagents from our catalogue.This new Acros Organics ACTA focuses on some verydifferent topics, and more will be covered in the future.

We trust that you noticed the many new reagents thathave been added to our product line over the past

year. The positive responses we received have alreadymade us decide to continue complementing our cata-logue with many more novelties in the near future.Please check our electronic catalogue on CD or Internet for updated information. And if you can nottrack the reagent you need, let us know: AcrosOrganics welcome any suggestion on how to improvethe quest for novel reagents.

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The synthetic equivalence of 2-(trimethylsilyl)thiazole(2-TST) 2 to the formyl carbanion stems from thesequential addition to the aldehyde carbonyl and thecleavage of the thiazole ring of the resulting hydrox-

yalkylthiazole. This formulation has been previouslyexploited for higher and rare sugar synthesis andmore recently for a-amino aldehyde homologation.

Owing to a facile halogen-metal exchange and subsequent transmeta-lation, 2-(trimethylsilyl)thiazole (2-TST)2 can be effectively preparedin multigram quantities (20-30 g) from 2-bromothiazole1 by a well-detailed and independently checked high yield procedure (85%) (1)(Scheme 1). 2-TST2 is a stable, moisture- and air-insensitive com-pound reacting with variousC -electrophiles under very mild condi-tions (from room temperature to -20 C) and in the absence of a cata-lyst to give the corresponding 2-substituted thiazoles in very good yields (2) (Scheme 2). A mechanistic rationale has been provided (3) toaccount for the unprecedented carbodesilyla-tion reactions of the heteroaryl silane2 with-out the agency of any added catalyst. On the

other hand desilylation of 2 does not occurunder mild basic conditions. This stability hasbeen conveniently exploited for the prepara-tion of 4- and 5-substituted thiazoles via selec-tive functionalization of the thiazole ring at C-4 and C-5 followed by desilylation (4).

The model reaction of 2 with the chiralalkoxy aldehyde3 (D-glyceraldehyde) togive the -hydroxyalkylthiazole4 in high yield and diastereoselectivity followed by theliberation of the homologue aldehyde5 (D-

erythrose) by cleavage of the thiazole ring,demonstrate the actual synthetic equivalenceof 2-TST2 to the formyl carbanion synthon(1) (Scheme 3). The cleavage of the thiazolering into the formyl group is carried out by an

expeditious and operatively simple one-pot protocol involvsequence of three high yield reactions, all occurring under aneutral conditions, i. e. N-methylation, reduction, and hydrolySince these operations are tolerated by a variety of substituen

protective groups and do not affect the stereocentres of the subthe scope of this thiazole-based synthesis of aldehydes (Thiazole- Aldehyde Synthesis ) has been proved to be quite large (6). Thhomologation of various chiral alkoxyaldehydes and dialdoseby the iterative addition-deblocking sequence, demonstrateremarkable implementation of this aldehyde synthesis in cadrate chemistry.

Earlier (9) and recent observations (10) have shown that the sthe diastereoselectivity of the addition of 2-TST2 to chiralN -protect-ed -amino aldehydes can be reversed to give eithersyn oranti -amino alcohols by the use of singly or doubly protected deriv

respectively (Scheme 4 and Table 1). Based on this tunable stelectivity, efficient syntheses of chiral building blocks of immolecules, such as the potent anticancer agent Taxol (11) anselective HIV protease inhibitor Ro-31-8959 (12) (Scheme been recently reported.

For the synthesis of N -benzoyl-3-phenylisoserine6, the Taxol side-chain, the installation of the hydroxyl group with the correctR- con-figuration was effectively achieved by syn stereoselective addition (ds

2-(Trimethylsilyl)thiazole A Versatile Formyl CarbanionEquivalent for Organic Synthesis

Dipartimento di Chimica,Laboratorio di Chimica Organica, Universit,

Via L. Borsari 46,44100 Ferrara, Italy

Acros Organics Acta 4 - 1998 3

Alessandro Dondoni

1

1. BuLi2. Me 3SiCl

2-TST,2

N

S SiMe3

N

S Br 85 %

Scheme 1

R

2

R-CHO

R2C=C=O

+

R-COCl

N

S SiMe3 N

S

N

R

O

N

S

CO2Et

N

NN

S-(CH2)n -CO2R

O

SOSiMe3

RR

N

SR

OSiMe3

CO2Et

OF3C

RCO2-(CH2) -COCl

N

SCF3

OSiMe3

R

n

Scheme 2


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95%) of 2 to the singly N -protectedN -benzoylphenylglycinal9 (13)(Scheme 6). The rest of the synthesis was straightforward since itrequired the protection of the amino alcohol10 by acetonization andthe release of the aldehyde11 by the usual thiazolyl-to-formyldeblocking protocol. The almost quantitative oxidation of 11 by

KMnO4in bufferedtert -butanol gave the oxazolidine-type protected3-phenylisoserine12 in 47% overall yield from L-phenylglycine, thechiral starting material employed for this synthesis. The same route was followed for the synthesis of theN -Boc analogue of 12, which hasalready proved (14) to be a convenient substrate for the construction of

the side-chain of Taxotere (15), a semisynthetic and more potent analogue of Taxol.

Given theanti relationship between theamino and hydroxyl group in theN -Boc--amino- -hydroxy-4-phenylbutanal7, key intermediate for the preparation of thehydroxyethylamine isosteric dipeptide8 (16)precursor of Ro 31-8959 (see Scheme 5), theaddition of 2-TST2 was carried out to thedoubly N -protected L-phenylalaninal13 (10)(Scheme 7). In addition to thetert -butoxycar-bonyl (Boc) that was required in the targetaldehyde7, the second amino protective

group was the p -methoxybenzyl (PMB) sincethis was expected to be easily and selective-ly removed. Theanti selective addition of 2 to13 (ds 75%) followed by simple elaborationsof the resulting main product14 (removal of PMB under oxidative conditions, protectionof the hydroxyl group, unmasking of theformyl group) afforded the aldehyde15, asilyl derivative of 7, in 25% yield from L-

phenylalanine, the chiral starting material of this synthesis.

In conclusion, the fortunate occurrence of a set of positive featu

bringing 2-(trimethylsilyl)thiazole2 to increasing attention (17) as a valuable reagent in heterocyclic chemistry and an efficient foanion equivalent (18) for organic synthesis.

References(1) Dondoni, A.; Merino, P.Org. Synth.1993, 72 , 21.(2) Dondoni, A.Pure & Appl. Chem.1990, 62 , 643; Dondoni, A.; Boscarato, A.;

Formaglio, P.; Bgu, J.-P.; Benayoud, F.Synthesis , 1995, 654.(3) Dondoni, A.; Douglas, A. W.; Shinkai, I. J. Org. Chem.1993, 58 , 3196.(4) 4a) Dondoni, A.; Mastellari, A. R.; Medici, A.; Negrini, E.; Pedrini, PSynthesis ,

1986, 757.4b) Dondoni, A.; Fantin, G.; Fogagnolo, M.; Medici, A.; Pedrini, P.Synthesis ,1987, 998.It is worth pointing out that the1H NMR spectra for 4- and 5-trimethylstan-nylthiazole reported in ref. 4a were inadvertantly interchanged. Thankdue to Professor T. R. Kelly (Boston College, Chestnut Hill, USA) for this mistake to our attention. See: Kelly, T. R.; Lang, F.Tetrahedron Lett.1995,36,9293.

(5) Dondoni, A.; Marra, A. ; Perrone, D. J. Org. Chem.1993, 58 , 275.(6) For the illustration of a wider scope of theThiazole-Aldehyde Synthesis by the

use of thiazole based intermediates bearing various structural arrays asee:6a) Dondoni, A. inNew Aspects of Organic Chemistry II , Yoshida, Z.;

Ohshiro, Y. Eds., Kodansha, Tokyo, and VCH, Weinheim,1992, p. 105.6b) Dondoni, A. inModern Synthetic Methods,Scheffold, R., Ed., VerlagHelvetica Chimica Acta, Basel,1992, p. 377.

(7) 7a) Dondoni, A.; Fantin, G.; Fogagnolo, M.; Medici, A.Angew. Chem. Int. Ed.Engl.1986, 25 , 835.

Acros Organics Acta 4 - 19984

2-(Trimethylsilyl)thiazole - A Versatile Formyl Carbanion Equivalent for Organic SynthesisAlessandro DondoniDipartimento di Chimica,Laboratorio di Chimica Organica, Universit,

Via L. Borsari 46, 44100 Ferrara, Italy

3

62%

5

OCHO

O

N

O

O

OH

N

SS SiMe3

1. NaH / BnBr

2. CF3SO3Me3. NaBH 44. HgCl2-H2O 2-TST, 2

4 (ds 95%)

96%

-CHO

O

O

CHO

OBn

Scheme 3

R CHO

N

S SiMe3

R S

N

OH

R S

N

OHno catalyst

2-TST, 2

anti syn

+

N N NBo c R ' Bo c R ' Boc R '

Scheme 4

Entry R R Yieldb syn : anti

%1 OCH2 CMe2 85 8 : 922 PhCH2OCH2 H 60 80 : 203 (R ) OCHMe CMe2 68 15 : 854 (R ) TBDPSOCHMe H 60 78 : 225 Ph PhCH2 67 40 : 606 Ph H 70 88 : 127 PhCH2 PhCH2 70 22 : 788 PhCH2 H 74 80 : 209 i -C4H9 PMB 81 25 : 7510 i -C4H9 H 75 77 : 2311 c -C10H11CH2 PhCH2 71 17 : 83

12 c -C10H11CH2 H 79 83 : 17aBoc = tert-butoxycarbonyl; TBDPS = tert-butyldiphenylsilyl; PMB = p -methoxybenzyl. All reactions were carried out in CH2Cl2at -20 to -30C; desilylative workup was carried out with Bu4NF in THF.bIsolatedchemical yields of mixtures of syn andanti amino alcohols.

Table 1: addition of 2-(Trimethylsilyl)thiazole 2 toN-Boc a-Amino Aldehydesa (see Scheme 4)


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7b) Dondoni, A.; Fantin, G.; Fogagnolo, M.; Me A.Tetrahedron 1987, 43 , 3533.7c) Dondoni, A.; Fantin, G.; Fogagnolo, M.; Medici

Pedrini, P. J. Org. Chem.1989,54,693.7d) Dondoni, A.; Orduna, J.; Merino, P.Synthesis 1992,201.

(8) The multigram synthesis of rare sugars such asD-taloseandL-gulose will be reported in a forthcoming publcation. Dondoni, A.; Marra, A. unpublished results.

(9) Dondoni, A.; Fantin, G.; Fogagnolo, M.; Pedrini, J.Org. Chem.1990, 55,1439.

(10) Dondoni, A.; Perrone, D.; Merino, P. J. Org. Chem.1995, 60, 8074.

(11) Nicolaou, K. C.; Dai, W.-M; Guy, R. K.Angew. Chem.Int. Ed. Engl.1994, 33 , 15.

(12)Drugs Future 1995, 20 , 321.(13) Dondoni, A.; Perrone, D.; Semola, T.Synthesis 1995,

181.(14) Bourzat, J. D.; Commeron, A.Tetrahedron Lett.1993,

34 , 6049.(15) Gunard, D.; Guritte-Voegelein, F.; Potier, P.Acc.

Chem. Res.1993, 26 , 160.(16) Parkes, K. E. B.; Bushnell, D. J.; Crackett, P.

Dunsdon, S. J.; Freeman, A. C.; Gunn, M. P.; HopkR. A.; Lambert, R. W.; Martin, J. A.; Merrett, JRedshaw, S.; Spurden, W. C.; Thomas, G. J. J. Org.Chem.1994, 59 , 3656.

(17) 17a) Hassner, A.; Stumer, C.Organic Syntheses Based on Name Reactions and Unnamed Reactions , Elsevier,Oxford,1994, p. 100.17b) Fieser, M.Reagents for Organic Synthesis , Wiley,New York,1992, Vol. 16, p. 362.17c) Maillard, Ph.; Huel, C.; Momenteau, MTetrahedron Lett.1992, 33 , 8081.17d) Wagner, A.; Mollath, M.Tetrahedron Lett.1993,34 , 619.17e) Khare, N. K.; Sood, R. K.; Aspinall, G. O.Can. J.

Chem.1994, 72 , 237.(18) Dondoni, A.; Colombo, L.Advances in the Use of Synthons in Organic Chemistry , Dondoni, A., Ed., JAIPress, London,1993.


2-(Trimethylsilyl)thiazole - A Versatile Formyl Carbanion Equivalent for Organic SynthesisAlessandro Dondoni

Dipartimento di Chimica,Laboratorio di Chimica Organica, Universit,

Via L. Borsari 46, 44100 Ferrara, Italy

Products available at ACROS ORGANICS

2-(Trimethylsilyl)thiazole, 96%................................................................................. [79265-30-8] 29229-0010 1 ml

........................................................................................................................................................... 29229-0050 5 ml 2-Bromothiazole, 98+% (GC) .................................................................................................... [3034-53-5] 1709

............................................................................................................................... ........................................ 17091Methyl trifluoromethanesulfonate............................................................................................... [333-27-7] 41501

OBz

AcO O OH

O

OAc

NHBz

PhCO2H

OHO

O

OH

Ph

NHBz

HO

OH

BocHN N

OH

H

H

O NHBu-t

Ph

6

CHO

Taxol

Ro 31-8959RPh

NHBoc

78

Scheme 5

N

S SiMe3two steps

74 %

9

KMnO4

O

HPh

NHBzNHBz

Ph N

S

OH

2-TST,2

75 %

O

BzN

CHOPh

11

O

BzN

CO2HPh

10 (ds 95%)

95%

12

Scheme 6

N

S SiMe 3

15

2-TST, 2

63 %

three steps

13

CHOPh

NBo c PMB

Ph

NBo c PMB

N

S

87 %OH

14 (ds 75%)

Ph

NHBoc

CHO

OSiMe2Bu-t

Scheme 7


6/20

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For the SAMP/RAMP-hydrazone method, the titlecompound 2,2-dimethyl-1,3-dioxan-5-one (Figure 1)proved to be a versatile C3-building block and dihy-droxyacetone equivalent in asymmetric synthesis.

Dihydroxyacetone phosphate (DHAP) isused in nature as a C3-methylene compo-nent in enzyme-catalyzed aldol reactions toform 2-ketoses. Until very recently, chemi-cal synthetic DHAP equivalents allowingthe transfer of this simple C3 building blockto electrophilic substrates by asymmetricsynthesis have not been available (1). Thetitle dioxanone1 (Figure 1) (2) in combina-

tion with the SAMP/RAMP-hydrazone method (3) has turned out to bebroadly applicable in this respect and can be used to carry out highly

diastereo- and enantioselective C-C bond formations.Transformation of 1 into the corresponding SAMP-hydrazone, togeth-er with -alkylation affords the hydrazones2, which are oxidatively cleaved to the -alkylated ketones3 in good overall yields and withexcellent enantiomeric excesses (2a,b,4). Furthermore, a second alky-lation of the monoalkylated hydrazones2 is possible in the same

manner, occurring regioselectively at the -position and withoutepimerization of the -stereogenic center. In this way, C2-symmetricketones4 are available in good overall yields and with virtually plete asymmetric induction (de, ee 98%) (Scheme 1) (4).

The remarkable synthetic flexibility of this procedure is demonby the use of two different electrophiles (boxed, Scheme 2), give rise to , -bisalkylated ketones5 of very high diastereo- andenantiomeric purity. For instance, after removal of the protgroups, thede novo synthesis of C5- to C9-deoxy sugars is possible(e.g.6, de, ee 95%). In addition, after reduction of the keto gro with lithium tri-sec-butylborohydride to7, the corresponding polyolsare also available (e.g.8, de, ee 95%) (Scheme 2) (5).

As is depicted in Scheme 3, the protocol can be further extenthe introduction of a nitrogen functionality, leading finally to h ylated piperidines (azasugars), potential glycosidase inhibitoinstance, the bromide azide substitution variant via9 leads to thepiperidine10 after intramolecular reductive amination and acetoncleavage. Alternatively, the oxirane azide ring opening variant11gives rise to the polyhydroxylated piperidine12 (6). It should also bementioned that 1,3-diols and polyols can be synthesized by redremoval of the keto group in compounds of type5 (7).

, -Bisbenzylation of 1, usingthe SAMP-hydrazone method,leads to the C2-symmetric ketone13 in 70% overall yield withpractically complete asymmetricinduction. This opens an effi-cient entry via the bistriflate14and bisazide15 to thediaminoalcohol16, which is animportant precursor of severalHIV-1 protease inhibitors, e.g. A-74704 of Abbott (Scheme 4) (8).

Finally, the synthetic utility of the title dioxanone1, is demon-strated in two efficient asymmet-ric syntheses of natural prod-ucts, namely the 18-memberedlichen macrolide (+)-aspicilin via17 (Scheme 5) (9) and L-threo -sphingosine, a subunit of many glycosphingolipids that

2,2-Dimethyl-1,3-dioxan-5-one A Dihydroxyacetone Equivalent for Asymmetric Synthesis

Institut fr Organische Chemie,Rheinisch-Westflische Technische Hochschule,

Professor Pirlet-Strae 1,52074 Aachen, Germany


D. Enders*, B. Bockstiegel,W. Gatzweiler, U. Jegelka,B. Dcker

O O

O

H3C CH3

Figure 1

O O

O

H3C CH3

O O

N

H3C CH3

O O

O

H3C CH3

R

N

OCH3

O O

O

H3C CH3

ee = 88 - 98 %cy = 32 - 71 %

R

1. SAMP, toluene2. t BuLi

3. RX

R

O3, CH2Cl2

1. t BuLi2. RX 3. O3, CH2Cl2

de,ee 98 %cy = 30 - 65 %

R

1 2 3

4

Scheme 1


8/20

mediate cell recognition events.One of the key steps in thesphingosine synthesis is the aldolreaction of 1 with racemic -phenylselenylpentadecanal tointroduce the unsaturated sidechain via18 (Scheme 6) (10).

In conclusion, from the few exam-ples presented here, it is evidentthat 2,2-dimethyl-1,3-dioxan-5-one constitutes a synthetically very useful C3-building block anddihydroxyacetone equivalent in

asymmetric synthesis.References(1) Enders, D.Enzymemimetic C-C

and C-N Bond Formations inStereoselective Synthesis , Ottow, E.;Schllkopf, K.; Schulz, B.-G.(Eds.), Springer Verlag, Berlin,1993, p. 63-90.

(2) a) Enders, D.; Bockstiegel, B.Synthesis 1989, 493-496.

b) Bockstiegel, B. dissertation,Technical University of Aachen,1989.c) Araki, Y.; Nagasawa, J.; Ishido, Y . J. Chem. Soc. Perkin Trans. I 1981, 12-23.

(3) a) Enders, D. inAsymmetric Synthesis , Morrison, J. D. (Ed.), Academic Press, Orlando,1984, vol. 3, p. 275-339.b) Enders, D.; Fey, P.; Kipphardt,H.Org. Synth . 1987, 65, 173-182,183-202.c) Enders, D.; Klatt, M. inEncyclopedia of Reagents for Organic Synthesis , Paquette, L. A.(Ed.), Wiley, New York,1995, inpress.


2,2-Dimethyl-1,3-dioxan-5-one - A Dihydroxyacetone Equivalent for Asymmetric SynthesisD. Enders*, B. Bockstiegel, W. Gatzweiler, U. Jegelka, B. Dcker Institut fr Organische Chemie,Rheinisch-Westflische Technische Hochschule, Professor Pirlet-Strae 1,52074 Aachen, Germany

O O

O

H3C CH3

O O

O

H3C CH3

R1R2

HO OH

O

H3COH

O O

OH

H3C CH3

H3COBn

HO OH

OH

H3COH

O O

O

R1 X R2 X

SAMP-hydrazonemethod

cy = 30 - 62 %

1. Pd-C, H22. 3 N HCl, MeOH

>95 %

de,ee 95 %

[ R1 = CH2OBn, R2 = Me ]

LiB[CH(CH3)C2H5]3H,

toluene68 %

1. 3 N HCl, MeOH2. Pd-C, H2

>95 %

de,ee 95 %

R1 = H, Me,

R2 = , CH2OBn,O O

5 6

7 8

Scheme 2

O O

O

H3C CH3

O O

O

H3C CH3

O O

O

H3C CH3

N3

N3HO

H3C

N

OH

H

OH

N

OH

H

OH

CH3

de = 98 %, ee = 85 %

4 steps

64 %

5 steps

45 %

1. Pd-C, H22. HCl, MeOH

1. Pd-C, H22. HCl, MeOH

HO

50 %

93 % *

de = 24 %, ee 95 %

9 10

11 12

Scheme 3

O O

O

H3C CH3

O O

O

H3C CH3

TfO OTf

OBn

Ph

N3 N3

OBn

Ph

Ph Ph Ph

PhH2N NH2

OH

PhPh

CbzValN NValCbz

OH

PhPh

tetramethyl-guanidiniumazide 85 %

Pd-C, H2,MeOH

73 %

de,ee 98 %

H H

de,ee 98 %


70 %

4 steps

83 %

de,ee 95 %

HIV-1 protease inhibitors

(R,R)-A-74704 (Abbott)

13 14

1516

Scheme 4


9/20

(4) Enders, D.; Gatzweiler, W.; JegelkaU.Synthesis 1991, 1137-1141.

(5) Enders, D.; Jegelka, U.Tetrahedron Lett . 1993, 34, 2453-2456.

(6) Enders, D.; Jegelka, U.Synlett 1992,999-1001.

(7) Enders, D.; Scharfbillig, I.; LampeC.; Jegelka, U. unpublished results.

(8) Enders, D.; Jegelka, U.; Dcker, BAngew. Chem . 1993, 105, 423-425;Angew. Chem. Int. Ed. Engl . 1993,32, 423-425.

(9) Enders, D.; Prokopenko, O. F.Liebigs Ann . 1995, 1185-1191.

(10) Enders, D.; Whitehouse, D.;Runsink, J.Chem. Eur. J . 1995, 1,382-388.


2,2-Dimethyl-1,3-dioxan-5-one - A Dihydroxyacetone Equivalent for Asymmetric SynthesisD. Enders*, B. Bockstiegel, W. Gatzweiler, U. Jegelka, B. Dcker

Institut fr Organische Chemie,Rheinisch-Westflische Technische Hochschule, Professor Pirlet-Strae 1,

52074 Aachen, Germany


2,2-Dimethyl-1,3-dioxan-5-one.....................................................................................[74181-34-3]30078-0010 1 g (S)-(-)-1-Amino-2-(methoxymethyl)pyrrolidine, 98% ............................................................ [59983-39-0] 25437Synonym: SAMP(R)-(+)-1-Amino-2-(methoxymethyl)pyrrolidine, 98% (GC).................................................. [72748-99-3] 27714

Synonym: RAMPtert.-Butyllithium, 1.5 M solution in pentane.............................................................................. [594-19-4] 18128............................................................................................................................... ........................................ 18128Lithium tri-sec-butylborohydride, 1M solution in THF .......................................................... [38721-52-7] 17645............................................................................................................................... ........................................ 17645

**

O O

O

H3C CH3

O O

O

H3C CH3

C13 H27


52 %

5 steps

L-threo -sphingosinede,ee 98 %

74 %

18

C13H27

O

SePh

OH

SePh

HO C13 H27

NH2

OH

Scheme 6

O O

O

H3C CH3

O O

O

H3C CH3

BnO OTBS

CH3

4 steps (52 %)

RAMP-hydrazonemethod

9 steps

O

O

OH

OH

OH

H3C

9

(+)-aspicilin

de 91 %, ee 96 %

26 %

17

Scheme 5


10/20

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the Formyl Carbanion equivalent:(S,E)-(-)-Methyl-4-(phenylmethoxy)-2-pentenoate isanother enantiopure starting material for organicsynthesis, with many useful applications such as theasymmetric synthesis of polyhydroxylated compoundsand branched chain sugars with high chemical yields.

the Dihydroxyacetone equivalent:Dihydroxyacetone Phosphate is used in nature as a C3-methylene component in enzyme catalyzed aldol reactionsto form 2-ketoses. Until very recently, chemical syntheticDHAP equivalents allowing the transfer of this simple C3building block to electrophylic substrates by asymetmetricsynthesis have not been available.

2,2-Dimethyl-1,3-dioxan-5-one, now available from AcrosOrganics, in combination with the SAMP/RAMP hydrazonemethod has turned out to be broadly applicable in thisrespect, and can be used to carry out highly diastereo- andenantioselective C-C bond formations.

Acros Organics now offers a series of original reagents, on which pioneering research and development was done by Prof. Dr. D. Enders and his team at the Rheinisch-Westflische Technische Hochschule in Aachen, Germany.

The following innovative chemical tools studied in their projects are now commercially available:

CH 3O

CH3

O

O

CH 3O

CH 3

O

OH

OHcat. O SO4

arabino(2,3-syn-3,4-anti)

+ xylo,ribo and xylo form sas minor diastomers

the stable Carbene equivalent:1,3,4-Triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylidine is a stable,crystalline solid, provided that exposure to oxygen and moistureis avoided.The reagent shows the characteristic behavior of a nucleophiliccarbene. It inserts into the O-H and N-H bonds of alcohols andamines, respectively yielding the corresponding alkoxytriazolinesor alkylaminotriazolines. Published reactions include reactionswith chalcogens, heterocumulenes, double activated bonds andformation of organometallic complexes.

N

N

N

N

N

N

N

N

O

PhNCO:

O

O O O O

O O

O O

CH 3 CH 3

CH 3

CH 3

CH 3 H 3C

H3C

H3 C

R

RR

O N

O

O

N OCH 3

1. SAMP, toluen e2. tBuLi3. RX

1. tBuLi2. RX 3. O 3, CH 2 CL2

O3, CH 2 Cl2ee = 88 - 98%

dd,ee > 98 %

Acros Organics new 30026 1,3,4-Triphenyl-4,5-dihydro-1H-1,2,4-triazol-5-ylideneAsk for your copy of our technical infosheet n 26 with many more applications

Acros Organics new 29954 (S,E)-(-)-4-Methyl-4-(phenylmethoxy)-2-pentenoateAsk for your copy of our technical infosheet n 37 with many more applications

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11/20

The camphor derivatives oxazoline-N-oxides haveproved to be versatile dipoles for asymmetric cycload-dition with electron-poor dipolarophiles andcyclopentadiene. The resulting cycloadducts have

been subsequently transformed into anti

-hydroxyketone, -lactone and carbonucleosides such asCarbovir and -hydroxy- -aminoacids.

Condensation of -hydroxylamino alcohols with orthoesters givesrise to oxazoline-N -oxides (1), which can be considered as chiral

equivalents of nitrile oxides. The development of an asymmetsion of this reaction, and further transformation of cycloadducstitutes a new versatile method providing access to a large vachiral compounds.

(+)-3-Hydroxylamino isoborneol4a (2) was prepared in three stepsfrom camphoroquinone1 (overall yield 70%) (Scheme 1).Condensation of the corresponding hydrochloride4b with variousorthoesters gave rise to oxazoline-N -oxides6a-6d (3, 4). Both rateand yield of these reactions were increased by the use of trimorthoesters in the presence of 4 molecular sieves as methano

enger. The fast hydrolysis of oxazo-line-N -oxides precluded their isola-tion and therefore these dipoles were directly submitted to cycload-dition reactions with various elec-

tron-poor dipolarophiles (Scheme2, table).

With 1,2-substituted electron-poordipolarophiles, the reaction is high-ly regio- and stereoselective,endo adducts7 being the only productsisolated. Better yields wereobtained with unsubstituted oxazo-line-N -oxide6a (entries 1-4). Thisdipole can be considered as a chiralequivalent of fulminic acid. ,

Unsaturated esters, sulfones,nitriles and nitro compounds arethe dipolarophiles of choice. Alkylmonosubstituted alkenes can alsobe used (5).Exo adducts7j and7n were isolated albeit in low yield inthe latter case (entries 10 and 14).

Further transformations of theadducts illustrated the usefulness ofthese cycloadditions. The estergroup in adduct7m has been con-

verted to a methyl group by asequence of classical reactions. Theresulting compound8 has in turnbeen submitted to a two step oxida-tive cleavage affordinganti -

Camphor Derivatives Oxazoline- N -oxidesNew Chiral Auxiliaries for Asymmetric [2+3] Cycloadditions

Laboratoire de Synthse des Substances Naturelles,associ au CNRS,

ICMO, Universit de Paris-sud,91405 Orsay, France


Y. Langlois

NHOH

OHO

O

NOH

O

NOHOH

a b c, d

a: NH2OH HCl, AcOK, EtOH, H2O. b: NaBH4 , EtOH. c: NaBH3CN, AcOH, THF. d: HCl, Et 2O.

1 2 34a4b : 4a, HCl

Scheme 1

NHOH,HCl

OHN

OR

O N

O

O R

R1

R2RC(OMe)3

R2R1

+

_

a: see table

4b

5

6a : R=H6b : R=Me6c : R=Pr 6d : R=(CH2)4OBn

7

a

Scheme 2

N

O

O Pr

t-BuO2C

Pr N

O

O Pr

Me

Pr N

O

O Pr

Me

Pr

O

N

O

HOPr

Me

Pr

O

N

OH

OH

_

Pr Pr OHO

_

+

+

a

b, c

d

e

a: LiAlH4, Et 2O. b: TsCl, C5H5N. c: LiAlH4 , Et 2O. d: mCPBA, CH2Cl2. e: HCl, MeOH

+

7m 8 9

10 2 11

Scheme 3


12/20

hydroxyketone11in good overall yield(64% from adduct7m ) (Scheme 3).

Conversely by the same hydrolyticprocess, adduct7n afforded-hydroxyketone12. This compound,after deprotection, led to13, aspiroketalic pheromone of Dacus oleae (3) (overall yield from7n: 78%)(Scheme 4).

Cyclopentadiene is also an efficientdipolarophile in such cycloadditions.Exo adduct14 is the only product iso-lated in that case (75%). Subsequentoxidative methanolysis led to ketalderivative16. Stereoselective reduc-tion followed by an acylation withmethylchloroformate afforded dicar-bonate17 which, by a known proce-dure, led to the antiviral carbonucleo-side Carbovir19 (6) (Scheme 5).

Adduct7b, after reduction and pro-tection of the primary alcohol, pro-duced21. Via oxidative hydrolysisthis compound led to aldehyde22, which was oxidized without isolationinto carboxylic acid23. Classical lac-tonisation and deprotection gave riseto-lactone24 as a model of a fami-ly of bioactive natural products (over-all yield from adduct7b: 62%)(Scheme 6) (7).

Finaly, nitro adducts such as7d wereeasily reduced to the correspondingamino derivatives. These compoundsare potential precusors of -hydroxy- -aminoacids and-hydroxy- -aminoalcohols (8).

In conclusion, the camphor deriva-tives oxazoline-N -oxides6 are power-ful dipoles for producing adducts7 with high regio- and stereoselectivi-ties. Adducts7 bearing masked alco-hol and keto groups have been trans-formed in high overall yield into alarge variety of chiral compoundsuseful for further syntheses.


Camphor Derivatives Oxazoline- N -oxides - New Chiral Auxiliaries for Asymmetric [2+3] CycloadditionsY. LangloisLaboratoire de Synthse des Substances Naturelles, associ au CNRS,ICMO, Universit de Paris-sud,91405 Orsay, France

N

O

O OBn

OBn

BnO OBn

OHO

O

O

+

HO

2a

b

a: mCPBA, MeOH, HCl. b: H2, Pd-C, MeOH

7n 12

13

3

Scheme 4

Entry Dipole Dipolarophile

Yield% Adduct

1 6a

Temp. c (Time h)

Solvent

CO2Bn 40 (8) CH 2Cl2 62 7a

R1 R2

Me

2 6a CO2Bn Pr 80 (18) PhMe 90 7b

3 6a CO2tBu Pr 80 (18) PhMe 80 7c

6a NO2 Bu 40 (2) CH2Cl2 70 7d

5 6b CO2Me Me 80 (5) PhMe 58 7e

6b CO2Bn Me 80 (2) PhMe 52 7f

7 6b CO2Bn Pr 40 (24) CH2Cl2 52 7g

8 6b SO2Ph Me 40 (30) CH2Cl2 42 7h

9 6d SO2Ph (CH2)2OBn 40 (60) CH2Cl2 25 7i

10 6b H (CH2)2OBn 100 (4) PhMe 50 7j

11 6c CO2Bn Me 40 (24) CH2Cl2 52 7k

12 6c CO2Me Pr 40 (48) CH 2Cl2 53 7l

13 6c CO2tBu Pr 80 (18) PhMe 63 7m

14 6d H (CH2)2OBn 80 (18) PhMe 23 7n

4

6

Table 1


13/20

References:(1) Ashburn, S. P.; Coates, R. M. J. Org.

Chem . 1984, 49 , 3127.(2) Baldwin, S. W.; McFayden, R.B.; Aub

J.; Wilson, J. D.Tetrahedron Lett . 1991,32 , 4431.

(3) Berranger, T.; Langlois, Y. J. Org. Chem .1995, 60 , 1720.

(4) For an alternative preparation of oxazoline-N -oxides from chiral-aminoalco-hols, see:Berranger, T.; Andr-Barrs, A.;Kobayakawa, M.; Langlois, Y.Tetrahedron Lett . 1993, 34 , 5079.

(5) For an intramolecular version of thisreaction, see:Kobayakawa, M.; Langlois, Y.Tetrahedron Lett . 1992, 33 , 2353.

(6) Berranger, T.; Langlois, Y.Tetrahedron Lett . 1995, 31, 5523.

(7) Dirat, O.; Berranger, T.; Langlois, YSynlett , 1995, 935

(8) Berranger, T.; Kouklovsky, C.; MauduiM.; Langlois, Y. unpublished results.


Camphor Derivatives Oxazoline- N -oxides - New Chiral Auxiliaries for Asymmetric [2+3] CycloadditionsY. Langlois

Laboratoire de Synthse des Substances Naturelles, associ au CNRS,ICMO, Universit de Paris-sud,

91405 Orsay, France


(+)-3-Hydroxylamino isoborneol hydrochloride ......................................................................... 30138-2500 250 mg d-Camphoroquinone.....................................................................................................[2767-84-2] 40275-0250 25 g Trimethyl orthoformate, 99% .......................................................................................................[149-73-5] 14866............................................................................................................................... ........................................ 14866............................................................................................................................... ........................................ 14866Trimethyl orthoacetate, 98%.......................................................................................................[1445-45-0] 21818............................................................................................................................... ........................................ 21818Sodium cyanoborohydride, 95+%............................................................................................[25895-60-7] 16855............................................................................................................................... ........................................ 16855Sodium borohydride, 99+%......................................................................................................[16940-66-2] 20005Dicyclopentadiene, 95%, stabilized with 150-200 ppm p-tert.-butylcatechol..............................[77-73-6] 15076-............................................................................................................................... ........................................ 15076............................................................................................................................... ........................................ 15076............................................................................................................................... ........................................ 150763-Chloroperoxybenzoic acid, 70-75%..........................................................................................[937-14-4] 25579(balance 3-chlorobenzoic acid and water).................................................................................................. 25579-0

N

OH

ON

O

O H

O

OH

OHOMe

MeOOCO 2Me

OCO 2Me

N

NN

NH

Cl

NH2

HON

NN

N

OH

NH2

_

+

(+)-Carbovir

+

+

a

b, c d, e

f, g

6a 14

15 16 17

18

19

a: 40 C, 24h, CH 2Cl2. b: mCPBA, CH2Cl2. c: CSA, MeOH. d: CSA, MeCN, H2O, NaBH4.e: ClCO2Me, C5H5N. f: Pd(PPh3)4, 18 , THF, DMSO. g: NaOH(1M).

Scheme 5

N

O

O H

BnO 2C

Pr N

O

O H

ROCH2

Pr H Pr

O OH

OBn

OOH

HO Pr

O OH

OBnO

O

Pr HO

+

a, b c, d

e f, g

a: LiAlH4, Et 2O. b: NaH, BnBr, Bu4NI, THF, DMF. c: mCPBA, CH2Cl2. d: HCl(2M), THF.e: NaClO2, H2O2, MeCN, H2O. f: PhSO2Cl, C5H5N. g: H2, Pd-C, AcOEt.

7b 20 : R=H

21 : R=Bn

22 15

23 24

Scheme 6


14/20

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15/20

In supramolecular chemistry, calixarenes have beenthe object of numerous developments over the last

few years (1,2). These molecules can be used as amolecular platform after functionalization (3). The p-

isopropylcalixarene series has been studied to a con-siderably less extent than the p-tert- butylcalixareneseries (4,5,6). However, these macrocycles (Fig. 1)present interesting properties of complexationbecause of the p-isopropyl group (7).

1. PreparationSome one step syntheses have been described in the literature. The p -isopropylcalixarenes are formed by the condensation of formalde-hyde and p -isopropylphenol in the presence of KOH (Table I), intetralin as solvent.

Vicenset al.(9,10) synthesized an asymmetric p -isopropylcalix[4]areneby cyclo-condensation (Fig. 2) of the trinuclear oligomer with 2,6-bis-bromomethyl-4-isopropyl-3-methylphenol.

2. Chemical modifications A few modifications of p -isopropylcalixarenes have been described inthe literature. Bourakhouadar (4) has prepared the acetates (Fig. 3).

The chlorination by gas of p -isopropylcalix[4,6,8]arene has been stud-ied in the solid state in mild conditions (11). Analyses have shown thatall the calixarenes react, the number of chlorine atoms introduced per

phenolic moiety usually varying between 2 and 3.3. Conformational propertiesThe conformational mobility of p -isopropylcalixarene (4) has beenstudied with temperature-dependent1H NMR spectroscopy.

For the p -isopropylcalix[4]arene, the Ar-CH2-Ar methylene protons, which are singlet at 60C, are transformed into a pair of doublets at5C : there is an AB system. The calixarene exists in the cone confor-mation at low temperature, and is interconverted when the tempera-ture increases (4). The free energy of activation for inversion is 14.8kcal / mol (1).

For the p -isopropylcalix[8]arene, a similarity (4) in the temperature-dependent1H NMR spectra is observed with the cyclic tetramer inCDCl3 : one singlet for the Ar-CH2-Ar methylene protons at 60C anda pair of doublets at 5C. Similar to the p-tert -butylcalix[8]arene, the p -isopropylcalix[8]arene presents a pleated loop conformation. The free

energy of activation for inversion between pleated loop confor15 kcal / mol. In pyridine, at low and at high temperature, onsinglet is observed for the methylene protons. The interconvercalix[8]arene cannot be blocked out at low temperature.

For the p -isopropylcalix[6]arene, conformational studies (4) shown that the calix[6]arene can exist in eight different confor(1). The calix[6]arene is more flexible than either the calix[4]calix[8]arene.

For the p -isopropyldihomooxacalix[4]arene, because of the presof one dimethyleneoxa bridge (Fig. 1), the size of the cavity isthe same as that of the calix[5]arene, but the flexibility is (1,4,12). The dihomooxacalix[4]arene adopts a cone conformlow temperature :1H NMR spectrum in CDCl3 contains two sets of pairs of doublets. The conformational flexibility increases wtemperature. On the other hand, the flexing of the dimethylebridge produces conformers in which the oxygen is either insoutside the cavity.

The asymmetric calix[4]arene presents the same conformationtion as the p -isopropylcalix[4]arene (9).

In summary, the different p -isopropylcalixarenes adopt the same conformations in solution as their homologs in the p-tert -butylcalixareneseries do.

4. Solid state inclusion complexesand applications

The p -isopropylcalix[4]arene, which crystallizes in the cone cmation, forms complexes (2,13) with chloroform (1:1) and p -xylene(1:1). But with p -xylene, heating of the complex causes half of guest molecules to be lost and a new complex (2:1) is produce

The Chemistry of thep -Isopropylcalixarenes

Reconnaissance et Organisation Molculaire et BiomolculaireUPRES A du CNRS. Laboratoire de Chimie Industrielle,

Universit LYON I, 43 boulevard du 11 Novembre 1918,69622 Villeurbanne Cdex, France


F. Vocanson and R. Lamartine

OH

CH 2

n

n = 4,6,7,8

OH

CH2

4

CH2-O

Figure1: p-isopropylcalixarenes andp-isopropyldihomooxacalix[4]arene


16/20

The p -isopropyldihomooxacalix[4]arene forms a complex (1:1) witho -xylene and adopts a cone conformation (14).

The properties of complexation of o -and p -xylene by thecalix[4]arenes have been used for studying the separation of xylenesby extractive crystallisation with cyclic tetramers (4,15). The two pre- vious calixarenes have been recrystallized from 1:1:1 mixtures of thethree xylene isomers. The different analyses, by 1H NMR and GasChromatography, have shown that p -isopropylcalix[4]arene extracts p -xylene with 86% selectivity and p -isopropyldihomooxacalix[4]areneextractso -xylene with 84% selectivity.m -xylene is only extracted by p -isopropylcalix[4]arene with 14% selectivity. Consequently, molecu-lar recognition is possible with these calixarenes.

The asymmetric calix[4]arene forms a complex (1:1) with acetone andadopts a cone conformation (9).

Single crystals of p -isopropylcalix[6]arene have been obtained by sloevaporation at room temperature of a solution of carbon disulfbenzene. The calixarene adopts a cone conformation (7) and for

(1:3) complex with benzene.

References(1) Gutsche, C.D. inCalixarenes , The Royal Society of Chemistry , Cambridge,

1989.(2) Vicens, J.; Bhmer, V. inCalixarenes, a versatile class of macrocycle , Kluwer

Academic Publishers, Dordrecht,1991.(3) Bhmer, V.Angew. Chem. Int. Ed. Engl.1995, 34, 713.(4) Bourakhouadar, M. Thesis, University Lyon - I1989.(5) Perrin, R.; Bourakhouadar, M.; Duchamp, C.C.R. Acad.Sci.Paris 1990, 310

srie II, 1053.(6) Vicens, J.; Pilot, T.; Gamet, D.; Lamartine, R.; Perrin R.C.R. Acad.Sci.Paris

1986, 302 srie II, 15.(7) Halit, M.; Oehler, D.; Perrin, M.; Thozet, A.; Perrin, R.; Vice

Bourakhouadar, M. J. of Incl. Phenom.1988, 6, 613.(8) Vocanson, F.; Lamartine , R. unpublished results.(9) Ueda, Y.; Fujiwara, T.; Tomita , K.I.; Asfari, Z.; Vicens, J. J. of Incl. Phenom.

1993, 15, 341.(10) Casabianca, H.; Royer, J.; Satrallah, A.; Taty-C., A.; Vicens, J.Tetrahedron Lett.

1987, 6595.(11) Lamartine, R.; Perrin, R.; Perrin, M.; Lecocq, S.; Duchamp, C.Mol. Cryst. Liq.

Cryst.1994, 248, 61.

(12) Vocanson, F.; Lamartine, R.Acros Organics Acta 1996, 2, 1, 6.(13) Perrin, M.; Gharnati, F.; Oehler, D.; Perrin, R.; Lecocq, S. J. of Incl. Phenom.1992, 14, 257.

(14) Suzuki, K.; Armah, A.E.; Fuj, S.; Tomita, K.I.; Asfari, Z.; Vicens, J.Chem. Lett.1991, 1699.

(15) Vicens, J.; Armah, A.E.; Fuj, S.; Tomita, K.I.; Asfari, Z. J. of Incl. Phenom.1991, 10,159.


The Chemistry of the p -IsopropylcalixarenesF. Vocanson and R. LamartineReconnaissance et Organisation Molculaire et Biomolculaire UPRES A du CNRS.Laboratoire de Chimie Industrielle,Universit LYON I, 43 boulevard du 11 Novembre 1918, 69622 Villeurbanne Cdex, France


4-Isopropylcalix[4]arene ............................................................................................. 29931-2500 250 mg 4-Isopropyldihomooxacalix[4]arene ......................................................................... 29935-1000 100 mg 4-Isopropylcalix[6]arene ............................................................................................. 29932-2500 250 mg 4-Isopropylcalix[8]arene ............................................................................................. 29933-2500 250 mg

OH OH OH

+

OH

OH

HOOH

OH

BrBr

Figure 2 : synthesis of asymmetric calix[4]arene

OCOCH3

CH2

n = 4,6,8

Figure 3 : p-isopropyl-calixarene acetates

Table I : synthesis pathways for p-isopropyl-calixarenes

P-isopropyl- Yield (%) ratio phenol/ Referencecalixarenes formaldehyde/KOH

Calix[4]arene 18 10 /10 / 0.26 4Bishomooxacalix[4]arene 14 18.2 / 31.7 / 1.55 5Calix[6]arene 54 10 / 10 / 1.3 4Calix[7]arene 4 6.23 / 20 / 1.9 8Calix[8]arene 31.2 10 / 30 / 0.26 4


17/20

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18/20

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information !


19/20

New reagents for chiral Synthesis


Meyers Bicyclic Lactams from Acros Organics

newproducts

ACROS ORGANICSN. V .Geel West Zone 2 Janssen Pharmaceuticalaan 3a B-2440 Geel, BelgiumTel.: +32(0)14/57.52.11 Fax: +32(0)14/59.34.34Internet: http://www.acros.be

above applications are documented in:D. Romo and A.I. Meyers, Tetrahedron,1991, 47, 9503-9569

A.I. Meyers in Stereocontrolled OrganicSynthesis, B.M. Trost, Ed Blackwell, 1994,145-175

C.J. Andres, P.H. Lee, T.H. Nguyen andA.I. Meyers, J.Org.Chem., 1995, 60,3189-3193

A.I. Meyers and L. Snyder,J.Org.Chem., 1993, 58, 36-42

A.I. Meyers and G.P. Bregnel,J.Chem.Soc.Chem.Comm., 1997, 1

Acros Organics is proud to offer you a new set of most useful reagents for the Synthesis of optically active

QUATERNARY CENTERS, CYCLOPENTENONES, CYCLOPROPANES, PIPERIDINES

ON

R 2

R 1

O

NH

NH

NH

NH

O

O

C O 2 Me

R 4 R 3 N

R 4

R 3

R 3

R 4

R 4

R 2

R 3

R 3

R 2

R 2 COO H

R 4 R 3O

O

O

R 2

O

R 5

R 2

R 3

Are you although more interested in optically active EPOXIDES ?Ask for your free copy of Acros Organics special Technical Information Sheet n 38 on our product 32758Poly-L-Leucine, the best reagent for a simple, quick and reproducible way to chiral epoxides.

The following Meyers Bicyclic Lactams are available from stock at Acros OrganicsCatalog n R1 R2 (+) or (-)

Saturated bicyclic lactams 32646 i -Pr Me (+)32649 i -Pr Me (-)32650 Ph Me (+)32651 Ph Me (-)32645 Ph Ph (+)

32652 Ph Ph (-)32653 Ph H (+)32654 Ph H (-)

Unsaturated bicyclic lactams 32655 i -Pr Me (+)32656 i -Pr Me (-)32647 Ph Me (+)32648 Ph Me (-)


20/20

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