Acros Organics

A Brief Overview of Cyclopropane Aminoacids . . . . . . . . . 1

Nick Kilenyi

acta

Organic Peroxides in Radical Synthesis Reactions . . . . . . . . 6

J. Meijer, A.H. Hogt and B. Fischer

(S)- and (R)-N-Boc-N, O-Isopropylidene--methylserinals . . . . . . . 9

A. Avenozaa, C. Cativielab, F. Corzanaa, J. M. Peregrinaa, D. Sucunzaa and M. M. Zurbanoa

Acros Organics journal for chemists

Spring 2002

ChiroTech product range now available exclusively through Acros Organics

First words
Much has happened since the last issue of Acros Organics Acta. We see new trends emerging every day, inside as well as outside the chemistry lab. These are very interesting times for a company like Acros Organics, and we are working hard to keep apace with all these trends. Our site in Belgium, for instance, witnessed an impressive expansion with the building of new warehouses and offices. The new catalogues that we published contain more than 2000 new additions, and more products are added every day. We initiated important collaboration projects with ChiroTech for our drug discovery product line, and with QUILL for ionic liquids, which play an important role in green chemistry. You will find more information on these novelties in this issue of the Acta. Today, more than ever, Acros Organics delivers more than just the content of a bottle. We hope you will enjoy this new issue of our Acta!

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N 1: Solid Phase synthesis of compound libraries and their application in drug discovery. N 2: From homogeneous to heterogeneous catalysis, recent advantages in asymmetric synthesis with nitrogen containing ligands. N 3: 1-Hydroxycyclopropanecarboxylic acid a readily available and efficient precursor. N 4: Silylated N-Tert-Butyl Aldimines: Versatile organosilicon reagents for polyenal synthesis. N 5: A complete range (C2 to C20) of fully synthetic sphingosines and ceramides. No 6: Organic Peroxides in Radical Synthesis Reactions. No 7: CuCl(OH).TMEDA: A Novel, Efficient Catalyst for Aerobic Oxidative Coupling Reactions. NEW No 8: The wonderful world of the bis(trimethylsilyl) ketene acetal reagents

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Nick Kilenyi
Cerise Chemtech sa/nv, Rue de Strasbourg 5, Da Vinci Science Park, B-1140 Brussels, Belgium.

A Brief Overview of Cyclopropane Aminoacids

Introduction
Cyclopropane aminoacids are defined for the purpose of this article as alpha-aminoacids with a bridging methylene group forming a cyclopropyl ring. There are two main families, colloquially named 2,3methanoaminoacids (1) in which the bridge is connected to the alpha-carbon, and 3,4-methanoaminoacids (2), in which it is one position further down the chain. Such compounds are of interest as natural products, and also as conformationally-restricted analogues of the proteinogenic aminoacids. It should be noted that substituted 2,3methanoaminoacids can exist in two diastereomeric forms, with the substituent either syn or anti to the nitrogen. No attempt has been made here to provide a comprehensive review of this important field. Instead, emphasis has been placed on the more recent work. Readers desirous of greater detail should consult the excellent review published in 1990 by Stammer (ref 1), and the original papers cited here. Coronamic acid (4, R=Et) is a component of the toxins coronatine (5), a plant toxin produced by Pseudomonas corona-facience. The lower homologue norcoronamic acid (R=Me) is found in norcoronatine. (ref 3)
Me

NH3+

CO2R

( 4)
O

NH

CO2H R

(5 )

NH3+ R CO2H R H

NH3+

Hypoglycine A and B (6), isolated from the Ackee fruit Blighia sapida, cause hypoglycaemia in Man and animals. (ref 4)
+ H 3N H CO2-

CO2-

(syn)

(anti)

(1 )

(6 )
H H 3N CO 2

(2 )

Applications of Cyclopropane Aminoacids

As alluded to above, cyclopropane aminoacids may be regarded as conformationally frozen analogues of the natural aminoacids. It is therefore of great interest to incorporate them in peptides in order to probe conformational spaces and reactivity. Enkephalins containing 2,3-methanophenylalanine showed very different binding affinities and selectivities compared with the native hormone. Furthermore, such peptides were resistant to hydrolysis by chymotrypsin and carboxypeptidase Y. (ref 5) The dipeptides N-benzoyl-Acc-Phe-OH and N-benzoyl-Acc-Pro-OH inhibited carboxypeptidase A in a timedependent manner indicative of irreversible covalent binding of the dipeptide to the enzyme. (ref 6) Incorporation of Acc into peptides favours folding of the backbone into a C-7 helix or a gamma-turn, unlike the acyclic aminoisobutyric acid residue Aib. (ref 7)

Naturally-Occurring Cyclopropane Aminoacids

The simplest, and perhaps most important cyclopropane aminoacid is the parent, 1-aminocyclopropane-1-carboxylic acid (3) (Acc). This compound, originally isolated from apples and pears, is the biogenetic precursor of the ripening hormone ethylene in plants. (ref 2)

NH3+

Plants
CO2-

(3)

Acros Organics Acta 9 - Spring 2002

Nick Kilenyi Cerise Chemtech sa/nv, Rue de Strasbourg 5, Da Vinci Science Park, B-1140 Brussels, Belgium.

A Brief Overview of Cyclopropane Aminoacids

References
1. Stammer, C. H. Tetrahedron 1990, 46, 2231 2. Fowden, L.; Lea, P. J.; Bell, E. J., The Non-Protein Aminoacids of Plants, Advances in Enzymology, ed. A. Meister, Wiley, New York, 1979, 117 3. Ichihara, A.,;Shiraishi, K.; Sato, H.; Sakamura,; S. Nishiyama, K.; Sakai, R.; Furusaki, A.; Matsumoto, T. J. Am. Chem. Soc. 1977, 99, 636

4. Eloff, J.N.; Fowden, L. Phytochemistry 1970, 9, 2423 and references therein 5. Mapelli, C.; Kimura, H.; Stammer, C. H. Int. J. Peptide Protein Res. 1986, 28, 347 6. Ner, S. K.; Suckling. C. J.; Bell, A. R.; Wrigglesworth, R. J. J. Chem. Soc. Chem. Commun. 1987, 480 7. Barone, V.; Franternali, B.; Cristinziano, P. L.; Lelj, F.; Rosa, A. Biopolymers 1988, 27, 1673.

Acros Organics Offer: NEW Cyclopropane amino acids

O OH N O O CH 3 CH3 CH 3

35380 (1R,2R)-N-BOC-1-Amino-2phenylcyclopropanecarboxylic acid

O OH N O O CH 3 CH3 CH 3

35379 (1S,2S)-N-BOC-1-Amino-2phenylcyclopropanecarboxylic acid

O OH N O O CH 3 CH3 CH 3

35381 (1R,2S)-N-BOC-1-Amino-2phenylcyclopropanecarboxylic acid

O OH N O O CH 3 CH3 CH 3

35382 (1S,2R)-N-BOC-1-Amino-2phenylcyclopropanecarboxylic acid

ADDITIONAL CYCLOPROPANE CARBOXYLIC ACIDS AND DERIVATIVES

11162 11163 34528 11835 12671 13046 13492 16445 17059 17068 17069 19816 20529 25534 27850 27851 30142 30143 23305 27520 30211 30963 33530 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Cyclopropanecarboxylic acid 98% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Cyclopropanecarboxylic acid chloride 98% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1,1-Cyclopropanedicarboxylic acid 98% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Ethyl cyclopropanecarboxylate 99% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methyl cyclopropanecarboxylate 98% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .trans-2-Phenylcyclopropane-1-carboxylic acid 95% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-(2,4-Dichlorophenyl)cyclopropanecarboxylic acid 95% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Diethyl 1,1-cyclopropanedicarboxylate 97% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-Phenyl-1-cyclopropanecarbonitrile 97% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-Phenyl-1-cyclopropanecarboxylic acid 97% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-(4-Chlorophenyl)-1-cyclopropanecarboxylic acid 99% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2-Methylcyclopropanecarboxylic acid 98% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .DL-3-Methylenecyclopropane-trans-1,2-dicarboxylic acid 98% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Dimethyl cis-1,2-cyclopropanedicarboxylate 98% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Dimethyl 1-methyl-trans-1,2-cyclopropanedicarboxylate 99+% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Dimethyl 3-methyl-trans-1,2-cyclopropanedicarboxylate 99% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-Amino-1-cyclopropanecarboxylic acid 99% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-Hydroxy-1-cyclopropanecarboxylic acid 98% . . . . . . . . . . . . . . . . . . . . . .Methyl 3-(2,2-dichlorovinyl)-2,2-dimethyl-(1-cyclopropane)carboxylate, cis/trans 99% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methyl (1R,3S)-2,2-dimethyl-3-(2-oxopropyl)-cyclopropaneacetate 96% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methyl 1-hydroxy-1-cyclopropane carboxylate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .1-(Aminocarbonyl)-1-cyclopropanecarboxylic acid 97% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Ethyl 1-hydroxycyclopropanecarboxylate 90%

Acros Organics Acta 9 - Spring 2002

Moncef Bellassoued and Jrme Grugier

Universit de Cergy-Pontoise, Laboratoire de Synthse Organomtallique associ au CNRS, 5 mail Gay Lussac, Neuville sur Oise, F-95031 Cergy-Pontoise Cedex

New organosilicon reagents

Bis(trimethylsilyl)ketene Acetals: Versatile Organosilicon Reagents for Aldolisation Reactions.
Since the work of Mukaiyama1 in 1974 on the aldol reaction using silylenol ethers, silylketene acetals have seen an explosive growth in their use as building blocks in organic synthesis. Among these new reagents, bis (trimethylsilyl) ketene acetals are now the organosilicon compounds of choice for type aldol condensations because of their ease of preparation, clean products and high selectivity. The direct homologation of aldehydes into unsaturated conjugated carboxylic acids with the introduction of two carbon atoms in the resulting chain is a very attractive reaction, since polyethylenic carboxylic acids are very useful intermediates in the total synthesis of natural products.
OSiMe3 Me3Si OSiMe3 OSiMe3 OSiMe3

CH2-CO2SiMe3 SiMe3

Me3Si

CO2SiMe3

33101

33105

33112

33111

Indeed, the condensation of reagent 33101 with a wide range of aldehydes in the presence of catalytic amount of catalyst takes place at room temperature to give the corresponding ,-ethylenic carboxylic acids in excellent yield and with a total E stereoselectivity2,3. Reagent 33105 has proven to be suitable for one pot four-carbon homologation of aldehydes4 and imines5. Silylated acetate6 33112 and crotonate7 33111 can be used for the construction of many important building blocks.
O CO2H

Queen Substance of Honeybee

OSiMe3 O O CHO

OSiMe3

+
OSiMe3

Me3Si OSiMe3

Queen Substance of honeybee was selected as a target for total synthesis of a natural product with the aim to demonstrate the utility of our organosilicon reagents. The following retrosynthetic scheme represents the most efficient total synthesis described up today. Thus, the Queen Substance has been prepared in seven steps in 34% over yield8.

(1) Mukaiyama, T.; Banno, K.; Narasaka, K. J. Am. Chem. Soc. 1974, 96,7503. (2) Bellassoued,M.; Gaudemar, M. Tetrahedron Lett. 1990, 31, 209. (3) Bellassoued, M.; Lensen, N.; Bakasse, M.; Mouelhi, S. J. Org. Chem. 1998, 63, 8785. (4) Bellassoued, M.; Gaudemar, M. J. Organometal. Chem. 1984, 263, C21. (5) Bellassoued, M.; Ennigrou, R.; Gil, R.; Lensen, N. Synthetic Commun, 1998, 28, 3955. (6) Bellassoued, M.; Dubois, J. E.; Bertounesque, E. Synthetic Commun, 1987, 17, 1181. (7) Bellassoued, M.; Ennigrou, R.; Gaudemar, M. J. Organometal. Chem. 1988, 338, 149. (8) Bellassoued, M.; Majidi, A. Tetrahedron Lett. 1991, 32, 7253.

Request your copy of the Review from Prof. Bellassoued of Bis(Trimethylsilyl)Ketene Acetals: A document with a lot of applications, references and many tables of results, complete with the comprehensive list of these organosilicon reagents available from stock at Acros Organics!

Acros Organics Acta 9 - Spring 2002

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J. Meijer, A.H. Hogt and B. Fischer

Akzo Nobel Polymer Chemicals Laboratory Deventer Zutphenseweg 10, PO Box 10, 7400 AA Deventer, The Netherlands.

Organic Peroxides in Radical Synthesis Reactions

Introduction
Radicals can be used as synthetic intermediates in reactions which are often difficult to accomplish by other means and which can selectively occur under very mild conditions. The protection of functional groups, often essential for synthetic sequences of ionic reactions, is mostly not required for radical reactions.1 Organic peroxides are a very versatile source of radicals that are formed after the thermally induced homolysis of the peroxide bond. The major radicalmolecule reactions are additions and SH2 reactions, e.g. H-abstraction, atom transfer, unimolecular reactions, e.g. decarboxylation, -scission and rearrangements, e.g. 1,5-H-abstraction.2 In synthesis reactions, undesired radical-radical reactions such as radical combination and disproportionation can be avoided by proper choice of the type of peroxide and reaction conditions. Another major application of organic peroxides in syntheses is oxidation, which is a non-radical reaction.3

Radical reactions with organic peroxides

Through homolytic scission organic peroxides primarily generate oxy-radicals: alkoxy-, acyloxy- and/or oxycarbonyloxy-radicals.4 Oxy-radicals can also be generated from peroxyesters, diacylperoxides and hydroperoxides by redox systems.5 (see Fig. 4).
Figure 4. Generation of oxy-radicals via peroxy-compounds.
O* O*

DTAP O* O C 16 H33 O O* DTBP R1OOR 2 CPDC MPDC O C14 H29 O O*

DCP BPO O O* O O H TBCPDC O O O* O*

BPIC

Oxidation reactions with organic peroxides

Peroxyacids are mostly used for the epoxidation of unsaturated compounds. Most important are the Baeyer-Villiger reaction of carbonyl compounds, oxidation of nitrogen and sulfur compounds3 (see Fig. 3). It is generally accepted that such oxidations are non-radical reactions.
Figure 3. Oxidation via peroxy-compounds.

An important reaction of alkoxy-radicals is -scission, and of acyloxyradicals decarboxylation, both reactions resulting in the formation of carbon-radicals. In contrast, alkoxycarbonyloxy-radicals do not show decarboxylation.4 (see Fig. 5).
Figure 5. Generation of carbon-radicals via peroxy-compounds.
* C2 H5

* H TBPIB TBPP *

R3N(O)

DTAP
R3N

CH 3*
R2S R2S(O)n=1,2

DTBP R1OOR 2 * BPO LPO

O O
EPOXIDATION

O O H

TBPEH

PEROXY ACID

BTMHP

R1C(O)R 2

* C11H23
R1C(O)OR 2

BAEYER-VILLIGER

Acros Organics Acta 9 - Spring 2002

J. Meijer, A.H. Hogt and B. Fischer Akzo Nobel Polymer Chemicals Laboratory Deventer Zutphenseweg 10, PO Box 10, 7400 AA Deventer, The Netherlands.

Organic Peroxides in Radical Synthesis Reactions

In the presence of a substrate, oxy-radicals (R-H) generate substrateradicals which may undergo combination reactions, addition reactions to unsaturated compounds or atom-transfer reactions. Examples of such reactions in practical applications are (see Fig. 6): combination of phenylisopropyl-radicals to 2,3-dimethyl-2,3-diphenylbutane, applied as flame-retardant synergist,6 addition of methylphosphorous mono-isobutyl ester to vinylacetic acid ethylester, used in the synthesis of the glufosinate herbicide,7 and atom transfer of bromine to a substituted tolyl-radical, yielding a flame retardant.8 In addition, oxy-radicals can be used for the racemization of optically active chrysanthemic acid or its ester used for the synthesis of pyrethrine insecticides.9
Figure 6. Reactions of oxy-radicals with substrates R-H.

Oxy-radicals can add to unsaturated compounds. They may also undergo competitive reactions such as -scission in case of alkoxyradicals, and decarboxylation in case of acyloxy-radicals. The formed carbon-radicals will in most cases also add to the unsaturated compounds.4,10

Concluding remarks
There are several important parameters for the choice of a peroxide for use in chemical syntheses. The physical and chemical stability affects the storage and handling properties, the temperature-dependent rate of decomposition determines the reactivity at the process conditions. The radicals formed after decomposition must be efficient for the desired radical reaction. Peroxides may also be selected for specific rearrangements or specific coupling reactions, which can introduce functional groups into substrates. Decomposition products of the peroxides have to be taken in account during the purification process. Organic peroxides are well established synthetic agents in the manufacture of many pharmaceutical intermediates, herbicides, insecticides and various other fine chemicals. Organic peroxides offer opportunities to reduce the number of reaction steps in synthetic routes applying classical synthetic procedures. Moreover, introduction of functional groups can be achieved by using special organic peroxides. In many cases these reactions are unprecedented in non-radical chemistry. Organic peroxides combine a number of interesting features for the application in organic synthesis: High purity Good solubility on most organic systems, enabling homogeneous reaction conditions Well defined and temperature controlled reactivity High efficiency Favorable cost/performance ratio

R1OOR2

R1O * *OR 2

R-H ABSTRACTION

R-R COMBINATION 2x

R1OH + HOR R*

X-Y

R-X

+
H

Y*

ATOM TRANSFER
Br X H

[Regitz and Giese, 1989-a]

R H

[Tosoh, 1999]

ADDITION
O O P O O

[Meiji Saika Kaisha, 1982]

Abbreviations
Code BPIC BPO BTMHP CPDC DCP DTAP DTBP EHP LPO MPDC TBCPDC TBHP TBPB TBPEH TBPIB TBPP Chemical name* Tert-butyl peroxy isopropylcarbonate (Trigonox BPIC) Dibenzoyl peroxide (Lucidol, Cadet) Bis(3,5,5-trimethylhexanoyl) peroxide (Trigonox 36) Dicetyl peroxydicarbonate (Perkadox 24) Dicumyl peroxide (Perkadox BC) Di-tert-amyl peroxide (Trigonox 201) Di-tert-butyl peroxide (Trigonox B) Bis(2-ethylhexyl) peroxydicarbonate (Trigonox EHP) Dilauroyl peroxide (Laurox) Dimyristyl peroxydicarbonate (Perkadox 26) Bis(4-tert-butylcyclohexyl) peroxydicarbonate (Perkadox 16) Tert-butyl hydroperoxide (Trigonox A) Tert-butyl peroxybenzoate (Trigonox C) Tert-butyl peroxy-2-ethylhexanoate (Trigonox 21) Tert-butyl peroxyisobutanoate (Trigonox 41) Tert-butylperoxy pivalate (Trigonox 25) CAS nr. 2372-21-6 94-36-0 3851-87-4 26322-14-5 80-43-3 10508-09-5 110-05-4 16111-62-9 105-74-8 53220-22-7 15520-11-3 75-91-2 614-45-9 3006-82-4 109-13-7 927-07-1
Acros Organics Acta 9 - Spring 2002

* Cadet, Laurox, Lucidol, Perkadox, Trigonox are tradenames of Akzo Nobel.

J. Meijer, A.H. Hogt and B. Fischer Akzo Nobel Polymer Chemicals Laboratory Deventer Zutphenseweg 10, PO Box 10, 7400 AA Deventer, The Netherlands.

Organic Peroxides in Radical Synthesis Reactions

References
1 Curran, D.P., Porter, N.A., Giese, B., Stereochemistry of Radical Reactions, VCH Verlagsgesellschaft, Weinheim, Germany (1996), pp. 1-22. 2 Ingold, K.U., Rate constants for free radicals in solution, in: Kochi, J.K. (Ed.), Free Radicals, Vol. I, Wiley, New York (1973), Chapter 11, pp. 37-112. 3 Rao, A.S. and Mohan, H.R., in: Burke, S.D. and Danheiser, R.L., Handbook of Reagents for Organic Synthesis, Oxidizing and Reducing Agents, Wiley, Chichester, UK (1999), pp. 84-89. 4 Kochi, J.K., Oxygen radicals, in: Kochi, J.K. (Ed.), Free Radicals, Vol. II, Wiley, New York (1973), Chapter 23, pp. 665-710 (a). 5 Kochi, J.K, Oxidation-reduction reactions of free radicals and metal complexes, in: Kochi, J.K. (Ed.), Free Radicals, Vol. I, Wiley, NY (1973), Chapter 11, pp. 591-684 (b). 6 Regitz, M. and Giese, B. (Eds.), C-Radikale Band E19a, Methoden der Organischen Chemie (Houben-Weyl), Thieme Verlag, Stuttgart (1989), pp. 547-548 (a). 7 Meiji Seka Kaisha, Ltd, European patent EP18415 (1982). 8 Tosoh Corp., Japanese patent JP 11130708 (1999). 9 Sumitomo Chemical Company, Ltd, European patent EP282221 (1992). 10 Regitz, M. and Giese, B. (Eds.), C-Radikale Band E19a, Methoden der Organischen Chemie (Houben-Weyl), Thieme Verlag, Stuttgart (1989), pp. 31-40 (b).

For the full review article by Meijer, Hogt and Fischer covering this as well as discussions on reactivity of organic peroxides and functionalization reactions with organic peroxides you can request your free copy of Acros Organics Review 6.

ORGANIC PEROXIDES FROM ACROS ORGANICS

34988 34993 21178 36131 34996 34974 34994 34977 34983 . . . . . . . . . . . . . . . . . . . . . . . . . .Dicumyl peroxide . . . . . . . . . . . . . . . . . . . . . . .Di-tert-butyl peroxide . . . . . . . . . . . . . . . . . . . . . . . . .Dibenzoyl peroxide . . . . . . . . . . . . .1,1-Di(tert-butylperoxy)cyclohexane . . . . . . . . . . . . . . . . . . . . . . .Cumyl hydroperoxide . . . . . . . . . . . . . . . . . . . . . . . . . . .Lauroyl peroxide . . .3,6,9-Triethyl-3,6,9-trimethyl-1,4,7-triperoxonane . .1,1--Di-(tert-Butylperoxy)-3,3,5-trimethylcyclohexane . . . . . . . . . . . . . . . . .2,2-Di(tert-butylperoxy)butane 34986 17014 34985 34981 34984 34989 34991 34990 18034 . . . . . . . . . . . . . . . . . . . . . .tert-Butyl peroxyacetate . . . . . . . . . . . . . . . . . . . .tert-Butyl peroxybenzoate . . . . . . . . . .tert-Butylperoxy 2-ethylhexyl carbonate . . . . . .tert-Butyl peroxy-3,5,5-trimethylcyclohexane . . . . . . . . . . . .tert-Butylperoxy isopropyl carbonate . . . . . . . . . . . .di(tert-butylperoxyisopropyl)benzene . . . . . . . . . . . . . . . . . . . . .tert-Butyl cumyl peroxide . . . . . . .2,5-Dimethyl-2,5-di(tert-butylperoxy)hexane . . . . . . . . . . . . . . . . . . . . .tert-Butyl hydroperoxide

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Please check our website http://www.acros.com for additional events where we will be present. A list of current events can be found on the event page. Meet Acros Organics at following events:
Event name
Informex ACS National Meeting Drug Discovery Technology Drug Analysis 2002 SECO 39 11th Fechem Conference Heterocycles in Bio-Organic Chemistry 27th European Peptide Symposium 14th International Symposium on Chiralty

Location
New Orleans (LA) Orlando (FL) Stuttgart Brugge Saint Jean de Monts Barcelona Sorrento Hamburg

Country
USA USA Germany Belgium France Spain Italy Germany

Date
26 February - 1 March 2002 8 - 10 April 2002 15 - 18 April 2002 21 - 25 April 2002 26 May - 1 June 2002 9 - 12 June 2002 31 August - 6 September 2002 8 - 12 September 2002

Are you organising a conference or an event that you would like Acros Organics to attend? Send your request to marketing@acros.com and we will get in touch with you.
8
Acros Organics Acta 9 - Spring 2002

A. Avenozaa, C. Cativielab, F. Corzanaa, J. M. Peregrinaa, D. Sucunzaa and M. M. Zurbanoa

(a) Departamento de Qumica, Universidad de La Rioja, Grupo de Sntesis Qumica de la Rioja, UA-CSIC, 26001 Logroo, Spain; (b) Departamento de Qumica Orgnica, Instituto de Ciencia de Materiales de Aragn, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain

(S)- and (R)-N-Boc-N,O-Isopropylidene--methylserinals

Preparation and Synthetic Applications
This report describes two procedures for the synthesis of (S)- and (R)-N-Boc--methylserinal acetonides 1 and 4. The application of both compounds as valuable chiral building blocks in the asymmetric synthesis of -methylamino acids 2 and 3 is also reported.

CHO

O NB oc 1

HO 2 C H2N 2

CO 2H NH 2 3

OHC

O BocN 4

Introduction
Over the last decade, there has been sustained interest in the development and use of chiral N-protected--amino aldehydes due to their wide utility in organic synthesis (1). While the (S)-N-Boc-N,O-isopropylidene serinal 5, Garner's aldehyde (2), and its enantiomer 6 are well known as chiral building blocks in stereocontrolled organic synthesis, it is only very recently the synthesis of their homologues 1 and 4 have become appreciated and their chemistry investigated (scheme 1).
Scheme 1

The AD reaction of Weinreb amide of 2-methyl-2-propenoic acid in the presence of AD-mix-a proceeded with excellent e.e. to yield the diol 7. The amide group of diol 7 was converted into the methyl ester group to obtain the corresponding diol in two steps: basic hydrolysis with LiOH/MeOH and subsequent esterification with AcCl in MeOH. This diol was transformed into its 2,3-cyclic sulfite 9 with thionyl chloride (scheme 2).
Scheme 2

O N O AD-mix- O N O O N
S

AD-mix-
S

CHO R NBoc

OHC R R BocN

O
R

O HO

OH OH 8

1: R = Me 5: R = H

4: R = Me 6: R = H

HO

In this context, and taking into account the special role that ,dialkylamino acids have played in the design of peptides with enhanced properties, we have focused our attention on the stereoselective synthesis of a-methylamino acids. Indeed, (S)- and (R)-methyl derivatives 1 and 4 can be regarded as ideal precursors for the synthesis of quaternary -methylamino acids.

1. LiOH 2. AcCl, MeOH 3. SOCl 2, CCl4 MeO 2C

R CO 2Me O S O O 9

10 1. NaN3 , DMF 2. chromatography

O O S O

Synthesis
The first synthesis (3) of the homologue of serinal 5, the (S)--methyl derivative 1, was achieved on a milligram scale starting from (S)-methylserine and using a similar procedure to that described for the synthesis of Garner's aldehyde (2). Furthermore, we described a new and more convenient synthesis procedure for (S)- and (R)--methylserinals 1 and 4 on a gram scale starting from (R)-2-methylglycidol (4). Nevertheless, the best method to achieved these serinals on a multigram scale starts from the Weinreb amide of 2-methyl-2-propenoic acid (5), which is easily obtained from the commercially available 2-methyl-2-propenoic acid (6)- and uses a stereodivergent synthetic route, that involves a Sharpless asymmetric dihydroxylation reaction (AD) (scheme 2).
S

HO

CO 2Me

MeO 2 C

OH

N3 11 1. H2, Pd-C 2. (Boc)2O, Na2CO3 3. DMP, BF3Et2O 4. LiAlH4 5. Swern 1

N3 12

4
Acros Organics Acta 9 - Spring 2002

A. Avenozaa, C. Cativielab, F. Corzanaa, J. M. Peregrinaa, D. Sucunzaa and M. M. Zurbanoa (a) Universidad de La Rioja, Grupo de Sntesis Qumica de la Rioja, UA-CSIC, 26001 Logroo, Spain; (b) Instituto de Ciencia de Materiales de Aragn, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain

(S)- and (R)-N-Boc-N,OIsopropylidene--methylserinals Preparation and Synthetic Applications

Reaction of sulfite 9 with NaN3 in the presence of DMF as a solvent gave a mixture of azido esters with a regioselectivity of 20/80 in favour to -azido ester 11. Once separated, -azido ester 11 was readily hydrogenated in the presence of Pd-C to give the corresponding amino ester, which was subsequently treated with (Boc)2O in a basic medium to get the N-Boc amino alcohol. This compound was converted into the corresponding oxazolidine by the use of 2,2dimethoxypropane (DMP) with BF3Et2O and the required building block (S)--methylserinal 1 was obtained from this oxazolidine in two steps involving a reduction-oxidation sequence (26% overall yield from olefin Weinreb amide, using 8 steps) (scheme 2). The other enantiomer, the (R)--methylserinal 4, was obtained using the same strategy described above and also starting from Weinreb amide of 2methyl-2-propenoic acid, but changing the chiral catalytic ligand to AD-mix- in the AD reaction (scheme 2).

Scheme 3

1 Ph 3PCH 3Br, KHMDS , THF

R

O NB oc 13 H2/Pd-C, AcOEt
R

O BocN 14

Et

Et

O NB oc 15 Sc(TfO)3 CH3 CN/H2O HOCH 2 Boc HN 17 1. Jones oxidation 2. HCl (conc.)/THF 3. Propylene oxide, EtOH HO 2C H2N 19
R R

O BocN 16

Synthetic applications
In order to demonstrate that (S)- and (R)-N-Boc--methylserinal acetonides 1 and 4 are valuable chiral building blocks in the enantioselective synthesis of -methyl -amino acids, we have recently reported their use as starting material in the preparation of enantiomerically pure -substituted alanines by transformation of the aldehyde group into ethyl, vinyl or ethynyl groups. In this methodology, the oxazolidine ring contributes the amino acid moiety and the stereogenic centre was already created in the starting material. However, more recently we also explored the fact that this oxazolidine ring can behave as an excellent chiral inductor to create another new stereogenic centre in the asymmetric Grignard addition reactions to aldehydes. In this way, the synthetic utility of both -methylserinals 1 and 4 as chiral building blocks has been proved in the synthesis of the four enantiomerically pure -methyl--phenylserines.
1. Reactivity of aldehyde group without generation of new stereogenic centres

Et

Et

CH 2OH NHBoc 18

Et

Et

CO 2H NH 2 20

Starting from (S)--mehylserinal 1 and (R)--methylserinal 4, and using five steps, we obtained both enantiomers of Iva 19 and 20 with an overall yield of 61% (scheme 3) (7). Olefination of aldehyde group was carried out under salt-free Wittig conditions using methyltriphenylphosphonium bromide and potassium bis(trimethylsilyl)amide (KHMDS) as base, obtaining olefin 13, which was hydrogenated using Pd-C to give oxazolidine 15. The cleavage of the acetonide moiety of 15 was achieved using Sc(OTf)3 (10 mol%) to obtain compound 17, which was converted into (R)-Iva 19 as follows. It was oxidized by treatment with Jones reagent to give the corresponding protected amino acid, which was then subjected to hydrolysis using a mixture of concentrated HCl and THF. Liberation of the amino acid from its hydrochloride salt was then achieved by treating with propylene oxide in ethanol to furnish (R)-Iva 19 in high yield. The enantiomer of (R)-Iva: (S)-Iva 20 was obtained using the same strategy but starting from 4 (scheme 3).

We have also developed a methodology that offers a straightforward route to the synthesis of ,-unsaturated -methyl -amino acids. Indeed, we have achieved the synthesis of four interesting quaternary -amino acids in enantiomerically pure form: (R)- and (S)-vinylalanines 23 and 24 and (R)- and (S)-ethynylalanines 29 and 30 (7). Starting from olefin 13, we carried out acid hydrolysis, obtaining the cleavage of the acetonide moiety and the hydrolysis of the N-Boc. The corresponding aminoalcohol hydrochloride was then protected with Boc2O to give 21. The transformation of this compound into the quaternary amino acid (R)--vinylalanine 23 was achieved according to the protocol described above to transform alcohol 17 into amino acid 19. The enantiomer (S)--vinylalanine 24 was obtained using the same strategy but starting from olefin 14 (scheme 4).

10

Acros Organics Acta 9 - Spring 2002

A. Avenozaa, C. Cativielab, F. Corzanaa, J. M. Peregrinaa, D. Sucunzaa and M. M. Zurbanoa (a) Universidad de La Rioja, Grupo de Sntesis Qumica de la Rioja, UA-CSIC, 26001 Logroo, Spain; (b) Instituto de Ciencia de Materiales de Aragn, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain

(S)- and (R)-N-Boc-N,OIsopropylidene--methylserinals Preparation and Synthetic Applications

Scheme 4

13 1. HCl 2. Na2 CO3 , Boc2O, H 2O-THF HOCH 2 Boc HN 21 1. Jones oxidation 2. HCl (conc.)/THF 3. Propylene oxide, EtOH HO 2C H2N 23
R R

14

CH 2 OH NHBoc

The synthesis of (R)- and (S)--ethynylalanines 29 and 30 also starts from (S)- and (R)--methylserinals 1 and 4, respectively, and involves seven steps with an overall yield of 32% (scheme 5). The aldehyde-toacetylene conversion was undertaken in two steps using a dibromovinyl intermediate (the Corey-Fuchs strategy). Methylserinals 1 and 4 were converted into the corresponding alkynes 27 and 28, using the vinyl intermediates 25 and 26 (scheme 5). The conversion of compounds 27 and 28 into (R)- and (S)-ethynylalanines 29 and 30 was achieved in the same way described above for the preparation of amino acid 19 from alcohol 17 (scheme 5).
2. Reactivity of aldehyde group with generation of a new stereogenic centre

22

CO 2H NH 2

24

In order to demonstrate the synthetic utility of both -methylserinals 1 and 4 as chiral building blocks in asymmetric synthesis with generation of a new stereogenic centre, we tried the reaction of these aldehydes with phenyl nucleophiles under different conditions (scheme 6) (8).
Scheme 6

Scheme 5

H
S

OH
R

Ph

1 CH Br3, tBuOK, PP h3, PhMe Br

R

4
S

CHO

phenyl nucleophile

NB oc 31 + HO
S

O NBoc

H
S

Br

Br

Br
S

1 O

Ph

NBoc

O NB oc 25 1. BuLi, THF, -78 C 2. HCl. 3. Na 2CO3, Boc2O, H2O-THF HOCH 2 Boc HN 27 1. Jones oxidation 2. HCl (conc.)/THF 3. Propylene oxide, EtOH HO 2C H2N 29
R S R S

O BocN 26

32

In general, the results obtained indicate that the model proposed to explain the diastereoselectivity observed in the nucleophile additions is similar to that described for Garner aldehyde (9). The only difference observed is a significant increase of diastereoselectivity in favor to 31. Starting from enantiomerically pure 31, which was obtained by the attack of PhMgBr on -methylserinal 1, we synthesised (2R,3R)-methyl--phenylserine 35 with an overall yield of 54% (8), using four steps: intramolecular cyclization in compound 31, promoted by the attack of the alkoxide ion on the carbonylic carbon of the Boc group to give the bicyclic compound 33, selective deprotection of the acetonide moiety of 33 by the action of BF32AcOH to give the corresponding oxazolidinone, subsequent Jones oxidation and acid hydrolysis. Liberation of the amino acid 35 from its hydrochloride salt was achieved by the propylene oxide method. The diastereoisomer (2R,3S)--methyl--phenylserine 36 was also obtained (8) starting from 31 but now by a different type of intramolecular cyclization that uses triflic anhydride to give the bicyclic compound 34, with inversion of configuration at the benzylic carbon.

CH 2OH NHBoc 28

CO 2H NH 2 30

Acros Organics Acta 9 - Spring 2002

11

A. Avenozaa, C. Cativielab, F. Corzanaa, J. M. Peregrinaa, D. Sucunzaa and M. M. Zurbanoa (a) Universidad de La Rioja, Grupo de Sntesis Qumica de la Rioja, UA-CSIC, 26001 Logroo, Spain; (b) Instituto de Ciencia de Materiales de Aragn, Universidad de Zaragoza-CSIC, 50009 Zaragoza, Spain

(S)- and (R)-N-Boc-N,OIsopropylidene-a-methylserinals Preparation and Synthetic Applications

Using the same strategy explained to prepare amino acid 35 from 33, the amino acid 36 was obtained from compound 34 in a 43% yield (scheme 7) (8).
Scheme 7

Scheme 8

4 Ph MgBr HO H
S

NaH, D MF

31

Tf2O

O Na H, DMF 37

Ph Tf 2O

NB oc
Ph O
S

H H O
S

Ph
S

N O 33

N O 34 1. BF32AcOH 2. Jones oxidation 3. HCl (conc.)/THF 4. Propylene oxide, EtOH

H O
R

Ph Ph O
R

H
R

N O 38

N O 39 1. 2. 3. 4. BF3 2AcOH Jones oxidation HCl (conc.)/THF Propylene oxide, EtOH Ph HOOC H2N 41
S R

Ph HOOC H2 N 35
R R

H OH HOOC H2N
R

H
S

Ph OH

H HOOC
S S

Ph OH

H OH

36

The enantiomers (2S,3S)- and (2S,3R)--methyl--phenylserines 40 and 41 were obtained using the same strategy described above in scheme 7, but starting from (R)--methylserinal 4 (scheme 8) (8).

H 2N 40

References
(1) Jurczak, J.; Golebiowski, A. Chem. Rev. 1989, 89, 149. (2) Garner, P.; Park, J. M. Org. Synth. 1992, 70, 18. (3) Alas, M.; Cativiela, C.; Daz-de-Villegas, M. D.; Glvez, J. A.; Lapea, Y. Tetrahedron 1998, 54, 14963. (4) Avenoza, A.; Cativiela, C.; Corzana, F.; Peregrina, J. M.; Zurbano, M. M. J. Org. Chem. 1999, 64, 8220. (5) Avenoza, A.; Cativiela, C.; Corzana, F.; Peregrina, J. M.; Sucunza, D.; Zurbano, M. M. Tetrahedron: Asymmetry 2001, 12, 949. (6) Nahm, S.; Weinreb, S. M. Tetrahedron Lett. 1981, 22, 3815. (7) Avenoza, A.; Cativiela, C.; Peregrina, J. M.; Sucunza, D.; Zurbano, M. M. Tetrahedron: Asymmetry 1999, 10, 4653. (8) Avenoza, A.; Cativiela, C.; Corzana, F.; Peregrina, J. M.; Zurbano, M. M. Tetrahedron: Asymmetry 2000, 11, 2195. (9) Williams, L.; Zhang, Z.; Shao, F.; Carroll, P. J.; Joulli, M. M. Tetrahedron 1996, 52, 11673.

Conclusion
We report a large scale and stereodivergent synthesis of the (S)- and (R)--methylserinals 1 and 4, starting from commercially available (R)-2-methylglycidol 7. These compounds have proved to be valuable starting materials in a new approach to the synthesis of different quaternary -methylamino acids. We have also developed the asymmetric synthesis of the four stereoisomers of -methyl--phenylserines, via the highly diastereoselective Grignard addition reactions of PhMgBr on the chiral aldehydes 1 and 4. Indeed, the oxazolidine ring of 1 and 4 has been exploited as the precursor of the amino acid moiety and, moreover, as chiral auxiliary to create another new stereogenic centre in the asymmetric reactions.

ADDITIONAL CYCLOPROPANE CARBOXYLIC ACIDS AND DERIVATIVES

16831 15127 21947 18977 19467 15695 11563 36389 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methacrylic acid (2-Methyl-2-propionic acid) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Acetyl Chloride, 98% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Acetyl Chloride, p.a. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Di-tert-butyl dicarbonate, 97% [(Boc)2O] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Di-tert-butyl dicarbonate, 99% [(Boc)2O] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Methyltriphenylphosphonium bromide, 98% . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .2,2-Dimethoxypropane, 98% [DMP] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .Scandium (III) trifluoromethanesulfonate [Sc(OTf)3]

12

Acros Organics Acta 9 - Spring 2002

INTERVIEW
with Professor Ken Seddon on Green Chemistry / Ionic Liquids

What is green chemistry all about ?

Green chemistry is all about reducing the number and amount of harmful chemicals that are used and/or generated in research and industry, by developing harmless, green chemicals and/or processes. This new field is all about minimising the amount of waste till the point where you end up with no waste at all.

Of course, it will take time. Some look at green chemistry as a very expensive approach, which is quite a narrow way to view the subject. Indeed, the opposite should be true. There is much more to it than that. If I look at the reactions I get whenever I give a lecture on green chemistry, it gives me a feeling that we will see the interest in this matter grow rapidly in the near future.

Where does green chemistry stand now ?

The green chemistry principle is still very much in its infancy, it has not yet penetrated the mainstream chemical lab in research or industry and is not yet part of the curriculum in the education of young chemists. However, there are good omens today that green chemistry is starting to pick up speed. For instance, the Royal Society of Chemistry in the U.K. now has a journal that is dedicated to this issue it is called quite aptly Green Chemistry. The April 2002 issue will be devoted to ionic liquids, for example. In addition, papers on the subject are being well cited, which is a good meter for the interest in the subject.

How did you get involved with

green chemistry?
The whole concept of green chemistry comes from Prof. Paul T. Anastas of the White House Office of Science & Technology Policy (OSTP). He wrote all the key textbooks on the subject and defined the terms we currently use. Anastas is also the one who defined the 12 basic principles of green chemistry. We owe him a lot. Another person that played an important role in the development of this subject is certainly Professor Roger Sheldon. He is currently the chairman of the editorial board of the Green Chemistry journal.

What does QUILL stand for?

QUILL is an acronym for the Queens University Ionic Liquids Laboratory. It is an industry-university collaborative research centre focusing on ionic liquids. It consists of a consortium of 20 industrial companies to support research on ionic liquids.

What do you think the influence

of green chemistry will be on organic chemistry ?
Well, I am pretty sure that it will revolutionise the way we are doing chemistry now. It is a new vision that creates lots of new challenges. For instance, it is much more difficult to selectively oxidise an organic substrate with O2, but it is possible, although it requires new approaches.

For a free copy of the new Ionic Liquids Handbook, fill in the fax form on page 16 or the registration form on the Internet: www.acros.com

NEW RESINS FROM ACROS ORGANICS FOR SOLID SUPPORTED CHEMISTRY

Solid Phase Synthesis
The use of polymer supports in organic synthesis is becoming well established as demonstrated by the massive increase in the number of publications referring to it.The key reported advantages for solid-phase synthesis being faster and simplified procedures for the generation of a large number of compounds (use of automation/ ease of purification of intermediates and products/ use of excess starting material). At Acros Organics, we understand that for a solid phase synthesis procedure to fulfill its advantageous promises, it is crucial to select the correct resin matrix and linker(s) for the reaction under consideration. A selection of polystyrene and TentaGel resins for solid phase synthesis with a broad variety of linker groups and narrow-range loading capacities has been recently introduced to our stock.

Solution Phase Synthesis

Solution phase synthesis, where a reactive, functional group specific scavenger, a reagent, a ligand, or catalyst is attached to a polymer support, has been a fast growing area of synthesis. This methodology takes advantage of new developments within the field of solid phase synthesis and adapts them to the existing vast repertoire of chemical reactions.A wide range of resins for solution-phase synthesis have been introduced to Acros Organics to respond to the needs of the organic chemist adopting solution-phase strategies in his synthesis.

A wide range of resins for Solid Phase and Solution Phase Synthesis have been introduced by Acros Organics.Visit www.acros.com for the latest additions.

New Ligands & Catalysts

NEW catalysts for Hydrolytic Kinetic Resolution: (R, R) and (S, S)(Salen)Co(III) acetate 1
Complexes 1 catalyze the kinetic resolution of racemic, terminal epoxides. This is a highly desirable reaction leading to the formation of a chiral diol and the unreacted epoxide enantiomer.1,2,3 The Co (III) acetate complexes are generated in situ from the corresponding salen Co (II) complexes 32995 and 32996 by reaction with 1-2 eq. of acetic acid and exposure to air.
O R

from Acros Organics

+ N O Co

+ N

O OAc

OH O R R + OH

(R,R) -1 H2O

NEW

H + N Co O

+ N O

H + N Co O

H + N O

32995

32996

References 1 Furrow, M. E.; Schaus, S. E.; Jacobsen, E. N. J. Org. Chem. 1998, 63, 6776. 2 Tokunaga, M.; Larrow, J. F.; Kakiuchi, F.; Jacobsen, E. N. Science 1997, 277, 936. 3 Jacobsen, E. N. Acc. Chem. Res. 2000, 33, 421.

To order a copy of the new Drug Discovery brochure, fill in the fax form on page 16 or the registration form on the Internet: www.acros.com

New offerings
We are pleased to announce that research quantities of the ChiroTech product range are now available exclusively through Acros Organics. These products can be ordered through your local Acros Organics distributor or via the internet at www.acros.com. Through this collaboration with ChiroTech, Acros Organics is able to provide an unmatched product offering and service level to assist you in your drug design and discovery research.

for drug discovery and research

Over 182 products have been introduced to our product range, including high added value building blocks, intermediates, and advanced intermediates such as multi-functional single diastereomer scaffolds suitable for elaboration into potential drug-like compounds. All compounds are offered with the assurance of robust scaleable processes to make larger quantities of material available at minimal lead times as your hit compound makes it from discovery to development.
NEW

A sample of NEW functionalized cyclopentane and piperidine scaffolds

ChiroTech is a registered trademark of Chirotech Technology Limited.

OH

OH

MeO2C
N CO2H.H2NBn Boc

NHBoc

MeO2C

NHBoc

N CO2Me Boc

OH

36201

36200

36235

OH 36233

A sample of NEW building blocks and advanced intermediates

O NH
F

NEW
NH2

For further information or for any questions, please contact Acros Organics at chirotech@acros.com For enquiries regarding larger quantities of ChiroTech products, please contact the ChiroTech Sales Administrator on +44 1223 728026, or e-mail sales@chirotech.com

O
MeO2C

OH

CO2H
H2N CO2 H

Me FmocHN

CO2H

36220

36208

36301

36217

36148

Acros Organics Acta 9 - Spring 2002

15

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A selection of peptide grade reagents, formulations, and solvents has been recently added to our product range and are listed below. ReadyMix products are peptide grade reagents and solvents in the most popular formulations used by the peptide synthesis chemists. They are now available from Acros Organics, in ready to use solutions or in kits containing pre-weighed amounts of activating agents and solvents to be mixed immediately prior to use.
Most Peptide grade solvents are available in 1l and 2.5 l bottles Ready Mix kits: convenient pack sizes no tedious preparation prepared with high quality reagents complete range of most popular mixes.

Peptide Grade Reagents, Solvents and Formulations

Product Nr. 35480 35483 0025 0025 Pack. Name 2.5L 2.5L Dichloromethane (DCM), peptide synthesis grade. N,N-Dimethylformamide (DMF), peptide synthesis grade. Specifications H2O (KF) max 0.005%. Residue on evaporation max 0.0005%. Free amines (Kaiser) max 0.0001%. Acidity max 0.001%. Water (KF) max 0.02%. Free amines (Kaiser) max 0.001%. Residue on evaporation max 0.001%. Formaldehyde max 0.002%. Water (KF) max 0.005%. Residue on evaporation max 0.001%. Peroxides (as H2O2) max 0.001%. Free amines (Kaiser) not detected. Water (KF) max 0.02%. Free amines (Kaiser) not detected. Residue on evaporation max 0.0005%. Water (KF) max 0.03%. Residue on evaporation max 0.002%. Free amines (Kaiser) max 0.001%. UV absorbance: 285nm max 0.065 AU. 300nm max 0.035 AU. 325nm max 0.010 AU. 350nm max 0.005 AU. Water (KF) max 0.03%. Residue on evaporation max 0.002%. Free amines (Kaiser) max 0.001%. Water (KF) max 0.01%. Prepared from peptide grade materials. Prepared from peptide grade materials.

35484 35486 35489

0025 1000 0025

2.5L 100ml 2.5L

Methyl sulfoxide (DMSO), peptide synthesis grade. 1,1,1,3,3,3- Hexafluoro-2-isopropanol (HFIPA), peptide synthesis grade. 1-Methyl-2-pyrrolidone, special automatic peptide synthesizer grade.

35490 35487 35491 35481

0025 1000 0010 1000

2.5L 100ml 1L 100ml

1-Methyl-2-pyrrolidone (NMP), peptide synthesis grade. 1,1,1,3,3,3- Hexafluoro-2-isopropanol, 10% in dichloromethane, ReadyMix, peptide synthesis grade. Piperidine, 20% in N-Methyl-2-pyrrolidone, ReadyMix, peptide synthesis grade. N,N'-Dicyclohexylcarbodiimide (DCC) 0.1M solution in Dichloromethane, ReadyMix, peptide synthesis grade. N,N'-Dicyclohexylcarbodiimide (DCC) 1.0M in N-Methyl-2-pyrrolidone, ReadyMix, peptide synthesis grade. HBTU 0.1M in (HOBT 0.45M in DMF) 1:1, ReadyMix, peptide synthesis grade. HOBT 0.5M in N,N-dimethylformamide, ReadyMix, peptide synthesis grade.

35482

2000

200ml

Prepared from peptide grade materials.

35485 35488

2000 2000

200ml 200ml

3 Bottles kit of pure HBTU, HOBT and DMF to be mixed prior to use to give 3.79%HBTU in [6.08%HOBT in DMF]. 2 Bottles kit of pure HOBT and DMF to be mixed prior to use to give 6.76% HOBT in DMF.

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ACROS ORGANICS
Geel West Zone 2 Janssen Pharmaceuticalaan 3a B-2440 Geel, Belgium Tel.: +32(0)14/57.52.11 Fax: +32(0)14/59.34.34

For more information, please contact your local dealer

ACROS ORGANICS USA

500 American Road, Morris Plains, NJ 07950 Tel.: 1-800-766-7000 Fax: 1-800-926-1166 Internet: http://www.fishersci.com (US orders only)

ACROS ORGANICS on-line

Internet: http://www.acros.com E-Mail: info@acros.com