,JCCCAT (6) 349-448 (1991)
`
`JOURNAL OF THE CHEMICAL SOCIETY
`
`Chemical Communications
`
`Number 6
`1991
`
`CONTENTS
`
`Andrew Gelling, John C. Jeffery, David C.
`Povey, Michael J. Went
`
`Mark F. Beatty, Clive Jennings-White, Mitchell
`A. Avery
`
`Jos6 Barluenga, Miguel Tomfis, AIfredo
`Ballesteros, Jian-She Kong, Santiago Garcia
`Granda, Enrique P~rez-Carrefio
`Jeffrey H. Byers, Thomas G. Gleason, Kyle S.
`Knight
`Arunabha Datta~ Ashok R. Saple, Ravindra Y.
`Kelkar
`T. Stanley Cameron, Robert C. Haddon, Saba
`M. Matter, Simon Parsons, Jack Passmore,
`Arthur P. Ramirez
`
`Jean-Claude Berthet, Jean=Francois Le Mar~chal,
`Michel Ephritikhine
`
`Andrew D. Abell, John Trent, Ward T.
`Robinson
`
`Joseph V. Smith, Joseph J. Pluth, Russell C.
`Boggs, Donald G. Howard
`R. Galarini~ A. Musco, R. Poutellini, A.
`Bolognesi, S. Destri, M. Catellani, M.
`Mascherpa, G. Zhuo
`Brian F. Go Johnson, Jack Lewis, Paul R.
`Raithby, Vijay P. Saharan, Wing Tak Wong
`
`Wolfgang A. Hoffmann, Rolf W. Albach~
`Joachim Behm
`Simon Parsons, Jack Passmore, Melbourne J.
`Schriver, Peter S. White
`
`Sulur G. Manjunatha, Srinivasachari Rajappa
`Tatsuya Nabesbima, Kazuhiko Moriyama,
`Yumihiko Yano
`Masaru Kimura, Masahiko Shimoyama, Shiro
`Morosawa
`
`David IL G. Crout~ David A. MacManus, Peter
`Critchley
`Alan H. Davidson, Nick Eggleton, Ian H.
`Wallace
`Sabine L. Flitsch, James P. Taylor, Nicholas J.
`Turner
`
`349
`
`351
`
`353
`
`354
`
`356
`
`358
`
`360
`
`362
`
`363
`
`364
`
`365
`
`367
`
`369
`
`372
`373
`
`375
`
`376
`
`378
`
`380
`
`Formation of Novel Bidentate and Crown Thioether Ligands via Dicobalt Alkyne
`Complexes
`
`Stereocontrolled Synthesis of (2S, 3S, 8S, 9S)-3-Amino-9-methoxy-2~6,8-
`trimethyl-10-phenyldeca-4E,6E-dienoic Acid (ADDA),a the Characteristic
`Amino Add of Microcystins and Nodularin
`
`A New Class of Fused 1,4-Diazepines: Synthesis of Substituted 8,Sa-
`Dihydrofuro[2,3-b][1,4]diazepin-2-ones
`
`Hexenyl Radical Cyclization via Phenyl selenide Transfer
`
`Effect of Zinc Incorporation on the Structurb of the Catalyst Precursor
`(VO)2H4P209
`The Synthesis, Characterization, X-Ray Crystal Structure and Solution ESR
`Spectrum of the Paramagnetic Solid, 4,5-Bis(trifluoromethyl)-l,2,3-trithiolium
`Hexafluoroarsenate: Implications for the Identity of ’l,2-Dithiete’ Cations
`(~IS-CsH4SiMe~)3UH: The First Stable Organouranium0v) Hydride
`
`Carboxy to Ketone Dimeric and Catemeric Hydrogen Bonding in a Keto Acid
`Phosphorane: X-Ray Structure of 6-Ethoxycarbonyl-5-oxo-6-
`(triphenylphosphoranylidene)hexanoic Acid
`Tschernichite, the Mineral Analogue of Zeolite Beta
`
`A New Synthetic Route to Polyheteroarenediylvinylenes
`
`Syntheses of Linked Ruthenium and Osmium Carbonyl CIusters containing a
`Bridging Oxalato Ligand: X-Ray Structures of [{Osa(~-H)(CO)~0}~(C~O4)] and
`[ {Rus(~I,-H)C(CO) 14}2(C204)]
`Reductive Aggregation of an Organorhenium Oxide: an Unusual Metal Chain
`Structure
`The Kinetics of the Qnantitative, Symmetry Allowed, Reverse Electron Demand
`Cycloadditions of the Pseudo-~,3-Dipole SNS+ with Alkynes and Nitriles; the
`Preparation and X-Ray Crystal Structures of NC~SNS~HAsF6 and ~NSNO-
`C~S(AsF6)2: the Precursor to a New Class of S2N~C-CN;S~’*~ (n = 0,i,2)
`Bicyclics
`
`From N-Nitroacetylproline to Leucylproline
`Rate-acceleratlng Metal Ion Effects on Decarboxylation of ~x-Keto Acids by a
`Thiazolium Ion bearing a Metal Binding Site
`The Formation of Aryltetralin Derivatives in the Photolysis of Two trans-
`Cinnamoyl Moieties at Both Ends of a Polyethylene Glycol Chain in the Presence
`of Lithium Perchloratc
`Stereoselective Galactosyl Transfer to cis~Cyclohexa-3,5-diene-l,2-diol
`
`The Stereoeontrolled Claisen Rearrangement of Tertiary AIlylic Sulphone Esters:
`Stereoselective Formation of Trisubstituted Double Bonds
`Synthesis of’a Novel Acceptor Snbstrate for a Mannosyl Transferase
`
`Lupin Ex. 1005 (Page 1 of 6)
`
`

`
`J. CHEM. SOC., CHEM. COMMUN.~ I991
`
`Lnciano Lattuada, Emanuela Licandro, Stefano
`Maiorana, Antonio Papagni
`
`Nicolaas J. R. van Elkema Hommes, Freidrich
`Bickelhaupt, Gerhard W. Klumpp
`J. F. Bartoli, O. Brigaud, P. Battioni~ D.
`Mansuy
`Michel A. Petit, Marcel Bouvet, Didier Nakache
`
`Masazo Niwa, Tetsu Ya~namoto, Nobuyuki
`Hlgashi
`Stuart R. Batten, Bernard F. Hoskins, Richard
`Robson
`Georg Siiss-Fink, Meinh~rd Langenbahn, Helen
`Stoeckli-I~vans, Dieter Naumann
`
`437
`
`438
`
`440
`
`442
`
`444
`
`445
`
`447
`
`2-Methyl-4-alkenyl-2,3-dihydroflirans by Cleavage of the Metal-Carbon Double
`Bond in e~,[3-Unsaturated 2-Oxacyclopentylidene Pentacarbonyl Chromium
`Complexes
`Dilithium Diphenyhnethanediide; Generation, Redox Relationship with Lithium
`Chlorodiphenylmethanide, Implication with regard to Aggregation
`Hydroxylation of Linear Alkanes Catalysed by Iron Porphyrins: Particular
`Efficacy and Regioselectivity of Perhalogenated Porphyrins
`Electrosynthesis of a New Molecular Semiconductor: Lithium Naphthalocyanine
`Radical
`pH-Responsive Plastic Optical Fibres Modified with Polyion Complexed
`Multibilayers Containing a Poly(methacrylic acid) Segment
`3D Knltting Patterns. Two Independent, Interpenetrating Rutile-related Infinite
`Frameworks in the Structure of Zn[C(CN)3]z
`Room-temperature Activation of Aliphatic C-H Bonds in Cyclohexane and
`Pentane by the System [Oso(CO)n(NCMe)]-Te(CF3)2: X-Ray Crystal Structure
`of [Os3(CO)~ {Te(C6H~)2}]
`
`AUTHOR INDEX
`
`Abell, Andrew D., 362
`Albach, Roll W., 367
`Arai, T., 410
`Avery, Mitchell A.,
`Balle~teros, Alfl~edo, 353
`Balm, Simon, 412
`Barco, Achille, 390
`Barluenga, Jos6, 353
`Bartoli, J. F., 440
`Basile, Tiziana, 391
`Batten, Stuart R., 445
`Battersby, Alan R., 384
`Battioni, P., 440
`Baum, Marc M., 431
`Beatty, Mark F., 351
`Bchm, Joachim, 367
`Belal, Arafa A., 402
`Benetti, Simonetta, 390
`Berscheid, Ralf, 414
`Berthet, Jean-Claude, 360
`Bickelhaupt, Freidrich, 438
`Boggs, Russell C., 363 :
`Bolognesi, A., 364
`Bouas-Laurent, Henri, 416
`Bouvet, Marcel, 442
`Brigand, O., 440
`Brotin, Thierry, 416
`Byers, Jeffrey H., 354
`Cameron, T. Stanley, 358
`Cassidy, Mark A., 384
`Catellani, M., 364
`Chang, Kieyoung, 394
`Cheng, Chien-Hong, 423
`Coche-Guerente, Liliane, 386
`Collet, Andre, 435
`Conroy-Lewis, Fiona M., 388
`Consiglio, Giambattista, 421
`Critchley, Peter, 376
`Crockett, Nigel, 384
`Crout, David H. G., 376
`Cunningham, D., 432
`Datta, Arunabha, 356
`Davidson, Alan H., 378
`Denis, J. M., 403
`Dennis, T. John, 4~2
`Deronzier, Alain, 386
`Desiraju, Gautam R., 426
`Destri, S., 364
`Desvergne, Jean-Pierre, 416
`Diseh, Raymond L,, 411
`Domen, K. 410
`
`Drouin, Jacques, 435
`Eggleton, Nick, 378
`Ephritikhine, Michel, 360
`Fages, FrEderic, 416
`Fallis, Ian, 402
`Farrugia, Louis J., 402
`Flitsch, Sabine L., 380, 382
`Foote, Jefferson, 419
`Fujimoto, Takahiro, 428
`Galarini, R., 364
`Gallagher, J. F., 4.32
`Galland, Bruno, 386
`Garcia Granda, Santiago, 353
`Gelling, Andrew, 349
`Gleason, Thomas G., 354
`Graham, Alan, 407
`Guillemin, J. C., 403
`Haddon, Robert C., 358
`Hara, Kenjl, 408
`Hare, Jonathan P., 412
`Herrmann, Wolfgang A., 367
`Higashi, Nobuyuki, 444
`Higgins, T., 432
`Hoskins, Bernard F., 445
`Howard, Donald ~., 363
`Jarvis, John, 419
`Jeffery, John C., 349
`Jennings-White, Clive, 351
`Johnson, Brian F. G., 365
`Kagabn, Shinzo, 408
`Kaneko, Chikara, 434
`Keeler, James, 419
`Kelkar, Ravindra Y., 356
`Kibayashi, Chihiro, 405
`Kimura, Masaru, 375
`King, Margaret A., 400
`Klumpp, Gerhard W., 438
`Knight, Kyle S., 354
`Kochi, J. K., 396
`Kong, Jian-She, 353
`Kong, Kwang-Cheng, 423
`Krote, Harold W., 412
`Labbe, Pierre, 386
`Lacombe, S., 403
`Langenbahn, Meinhard, 447
`Lattuada, Luciano, 437
`Lau, W., 396
`Le Margehal, Jean-Francois,
`360
`Leeper, Finian J., 384
`Lewis, Jack, 365
`
`Li, Can, 410
`Licandro, Emanuela, 437
`Longobardo, Luigi, 391
`Lueht, Brett L., 400
`McArdle, P., 432
`Macdonald, Norman M., 402
`Machinaga, Nobuo, 405
`MacManus, David A., 376
`Maiorana, Stefano, 437
`Manjunatha, Sulur G., 372
`Mansuy, D., 440
`Maruya, K., 410
`Mascherpa, M., 364 .....
`Mattar, Saba M., 358
`Motet, MaSsilno, 421
`Moriyama, Kazuhiko~ 373
`Morosawa, Shiro, 375
`Moutet, Jean-Claude, 386
`Musco, A., 364
`Nabeshima, Tatsuya, 373
`Nakache, Didier, 442
`Naumann, Dieter, 447
`Neuhaus, David, 419
`Niwa, Masazo, 444
`Onishi, T., 410
`Ozaki, Shoichiro, 428
`Papagni, Antonio, 437
`Parsons, Simon, 358, 369
`Passmore, Jack, 358,369
`Peacock, Robert D., 402
`Pearson, Anthony J., 392,394
`Pdrez-Carrefio, Enrique, 353
`Petit, Michel A., 442
`Pfiste>Guillouzo, G., 403
`Pisano, Carmelina, 421
`Pluth, Joseph J., 363
`Pollini, Gian P., 390
`Pontellini, R., 364
`Poss, Mitchell J., 400
`Povey, David C., 349
`Pu, Lyong Sun, 429
`Raithby, Paul R., 365
`Rajappa, Srinivasachari, 372
`Ramirez, Arthur P., 358
`Raln6n, Diego J., 398
`Reverdy, Gilbert, 386
`Richmond, Thomas G., 400
`,Robinson, Ward T., 362
`Robson, Richard, 445
`Saharan, Vijay P., 365
`Sakaki, Jun-ichi, 434
`
`Sakane, Kazuo, 425
`Sakata, Y., 410
`Sankararaman, S., 396
`Saple, Ashok R., 356
`Sato, Masayuld, 434
`Schnik, Wolfgang, 414
`Sehriver, Melbourne J., 369
`Schulman, Jerome M., 411
`Sheerin, D., 432
`Shimoyama, Masahiko, 375
`Shinohara, Tomoichi, 428
`Simpson, Stephen J., 388
`Sironi, Angelo, 421
`Smith, Edward H., 431
`Smith, Joseph V.; 363
`Spalluto, Giampiero, 390
`Srinivasan, Kumar, 392
`Stoeckli-Evans, Helen, 447
`Sugita, Yoshiaki, 434
`Sttss-Fink, Georg, 447
`Tagliavini, Emilio, 39i
`Takahashi, Junko, 408
`Taylor, James P., 380, 382
`Taylor, Roger, 412
`Titman, Jeremy J., 419
`Tomfis, Miguel, 353
`Trent, John, 362
`Trmnbini, Claudi.o, 391
`Turner, Nicholas J., 380, 382
`Umani-Ronehi, Aehille, 391
`UtermOhlen, Ralf, 416
`van Eikema Hommes,
`Nicolaas J. R., 438
`Vidal, Jo~lle, 435
`V6gtle, Fritz, 414
`Wahab Allaf, A., 412
`Wallace, Ian H., 378
`Walton, David R. M., 412
`Watanabe, Yutuka, 428
`Went, Michael J., 349
`White, Peter S., 369
`Williams, D, .Lyn H., 407
`Wong, Wing Tak, 365
`Yamamoto, Tetsu, 444
`Yano, Yumihiko, 373
`Yasuda, Nobuyoshi, 425
`Yus, Miguel, 398
`Zanirato, Viniclo, 390
`Zhuo, G., 364
`
`COPYRIGHT THE ROYAL SOCIETY OF CHEMISTRY, 1991
`
`iii
`
`Lupin Ex. 1005 (Page 2 of 6)
`
`

`
`The Royal Society of Chemistry
`Journal of the Chemical Society, Chemical Communications
`
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`
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`
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`
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`
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`For Notice to Autho,’s, see Issue No. 1, pp. 1--5,
`
`Lupin Ex. 1005 (Page 3 of 6)
`
`

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`426
`
`J. CHEM. SOC., CHEM. COMMUN., 1991
`
`c*-attack
`
`~-attack
`
`l
`
`, ,
`
`°
`
`R
`
`o
`
`0 :~ ’~_NH OR
`
`Fig. 2 Reaction pathway for novel oxycarbonyl rearrangement
`
`orientation of nucleophilic attack of the flee nitrogen. In order
`to determine this orientation, we attempted an MNDO
`conformational analysis. In the case of attack at the c~-
`carbonyl carbon, a chair-like conformer (A), containing the
`bulky isopropyl moiety (Pri) in a pseudoequatorial orienta-
`tion, is the most favoured conformation and leads to the
`R-ester, In the case of attack at the ~-carbonyl carbon, a
`chair-like conformer (B) containing Pri in a pscudoaxial
`orientation is the preferred one and leads to the S-ester. Their
`MNDO-ealeulated optimized conformations and heats of
`formation are shown in Fig. 3 (a) and (b). As a result, A is the
`most favoured conformation, and the energy difference
`between A and B was calculated to be 0.942 kcal reel-t (1 cal
`= 4.184 J). This energy difference corresponds well with the
`stereoselectivity (ca. 80% at room temp.) in this reaction.
`We thank Dr Akito Tanaka for conformational analyses by
`the MNDO method and Dr Toshiji Tada for the single crystal
`analyses.
`
`Re¢eived, 1st October 1990; Com. 0/04411C
`
`References
`1 Y. Kuroda, M. Okuhara, T. Gore, M. Yamashita, E. [guchi, M.
`Kohsaka, H. Aoki and H. Imanaka, J. Antibiot., 1980, 33,259.
`2 Y. Kuroda, M. Okuhara, T. Goto, M. Okamoto, M. Yamashita,
`M. Kohsaka, H. Aoki and H. Imanaka, J. Antibiot., 1980, 33,267.
`3 L. Chaiet, B. H. Arisen, R. L. Monaghan, J. P. Spinge, J. L. Smith
`and S. B. Zimmerman, J. Antibiot., 1984, 37, 207.
`4 C. R. Johnson and T. L. Marten, Tetrahedron Lett., 1987, 28, 27.
`5 M. Fujino, S. Kobayashi, M. Obayashi, T. Fukuda, S. Sh~nagawa
`and O. Nishimura, Chem. Pharm. Bull., 1974, 22, 1857.
`
`AfH =-190.253 kcal mol-I
`(b) :
`
`AfH = -189.311 kcal mol-~
`Fig. 3 (a) Stereoview of conformer A; (b) stereoview of conforlne~ B
`(MNDO calculations)
`
`highly stabilized carbanion, which would be immediately
`prot0nated from the resultant oxycarbonylammonium
`species, as shown in Fig, 2. Therefore, the stereochemistry at
`the newly formed Chiral centre would be determined by the
`
`Hydration in Organic Crystals: Prediction from Molecular Structure
`
`Gautam R. Desiraju
`School of Chemistry, University of Hyderabad, P.O. Central University, Hyderabad 500 134, India
`
`The proportion of non-ionic, metal free, organic compounds that crystallise as hydrates increases, within the class,
`with an increase in the number of hydrogen-bond accepter groups with respect to the donor groups.
`
`The inclusion of water within organic crystals is a matter of
`both fundamental and practical importance and is quite unlike
`the inclusion of other solvents of crystallisation. Because of its
`small size and excellent hydrogen bonding ability, water is
`almost never an innocuous bystander in an organic crystal
`
`structure. With the recent impetus in crystal engineering,1
`there has been much interest in the prediction of crystal
`packing2-4 and hydrogen bond patternss using simple mol-
`ecular descriptors. Such efforts have been greatly facilitated
`by the existence of machine-readable databases such as the
`
`Lupin Ex. 1005 (Page 4 of 6)
`
`

`
`J. CHEM. SOC., CHEM, COMMUN., I99I
`
`427
`
`80
`75
`70
`65
`60
`55
`50
`45
`40
`35
`30
`25
`20
`15
`10
`5
`
`Fig. 1 Hydrogen bonding schemes for hydrated acid 1 (a) and
`anhydrous acids 2, 3 and 4 (b). In acid 1, the water molecules are also
`hydrogen bonded to nitro groups which are not shown here.
`
`Cambridgc Structural Database (CSD).6"Accordingly, this
`communication deals with the prediction of the likelihood of
`an organic molecule to crystallise as a hydrate.
`Water is incorporated into organic crystals far more
`frequently than other conrmon solvents. Of the 69 691 entries
`in the 1988 (3.1) version of the CSD, 33 886 do not contain any
`metal atom and of these, 3696 are solvates. It is appropriate to
`consider only those entries without metal atoms since water
`enters the coordination sphere of transition metal ions so
`readily. Even when these ’pure’ organics are surveyed, the
`number of entries having water of crystallisation is far in
`excess of the number having other solvents. The following
`statistics were obtained: water (2566); methanol (306); diethyl
`ether (175); benzene (173); ethanol (168); acetone (108);
`chloroform (102); others (98). These figures are striking
`because water is not a particul..arly good solvent for organic
`compounds and also because of the possibly comparable
`frequencies with which any of the above common solvents
`were used for crystallisation.
`This study was prompted by the observation that 3,5-
`dinitrosalicylic acid 1 crystallises as a monohydrate while the
`related compounds salicylic acid 2, 5-nitrosalicylic acid 3 and
`3-amino-5-nitrosalicylic acid 4 form anhydrous crystals.7 In all
`four structures, the phenolic hydroxy group is intramol-
`ocularly hydrogen bonded to the carbonyl oxygcn of the
`carboxy group and does not seem to play any differentiating
`role. The crystal structure of 1 is unusual in that, unlike 2, 3
`and 4, the molecules do not form centrosymmetric hydrogen
`bonded dimers but rather form hydrogen bonds along a
`catemer in which water molecules connect carbonyl and
`carboxy oxygen atoms (Fig. 1). These water molecules act in
`effect as hydrogen bond donors to the former (O . . , O 2.92
`A_) and as hydrogen bond acceptors from the latter (O . . . O
`2.52 A). Normally the catemer motif is not accessible to
`aromatic carboxylic acids for steric reasons,s In the structure
`of 1, however, water molecules acts as spacers so that the
`aromatic rings move sufficiently apart to avoid repulsive
`contacts with the catemer itself, Now, the interesting question
`is why this unusual structure is adopted at all. A possible
`rationale is obtained by considering that the number of
`hydrogen bond donors (two) and acceptors (seven) in acid 1 is
`quite unbalanced, It has been stated that all good proton
`donors and acceptors are used in hydrogen bonding.S If this is
`the case, three-centre interactions9 would appear inevitable in
`order that the maximum number of acceptors be included in
`the hydrogen bonding scheme. However, an alternative
`possibility to redress the donor : acceptor imbalance is by the
`
`0.2
`
`1.2 1.4 1.6 1.8 2.0
`Donor / Acceptor Ratio (d/a)
`
`Fig, 2 Histogram of donor/acceptor ratios (d/a) for 413_ hydrated
`crystal structures. Compounds are metal-free and not salts.
`
`inclusion of one or more water molecules. In the present case.,
`the 2:7 donor:acceptor ratio becomes a 4:8 ratio in the
`monohydrate. This possibility is an attractive one since
`stronger hydrogen bonds would be formed; this is so because
`not as many of them need be of the three-centre type.
`The next step in the analysis was to extend the argument
`with the CSD. From the 2566 hydrates mentioned above, salts
`and cyclodextrins were excluded. It is not surprising that
`charged species should crystallise as hydrates, while it may be
`easy for water molecules to _enter the large cavities of the
`cyclodextrins. Since, at this stage, the structures had to be
`examined manually (and individually) in order that the
`number of hydrogen bond donors and acceptors in the
`molecular structure be counted, a smaller group of 411
`structures was selected. To avoid any bias the structures were
`chosen according to journal.~"
`The following groups were defined as proton donors (d): 1°
`(primary) amine (2 donors); 2° amine (1); 1° amide (2); 2°
`amide (1); imine (!); alcohol, phenol, carboxylic acid,
`sulphonic acid (1). The following were defined as proton
`acceptors (a): N in amine, amide, imine (1); O in hydroxy and
`carboxy (1); sp30 in ethers and esters (1); sp20 in carbonyl
`compounds (1); O in nitro (2); N in nitrile and isonitrile (1); F
`in a C-F bond was not included as a proton acceptor.
`B arring a single structure,~0 all the selected hydrates contain
`grodps capable of participating in hydrogen bonding. Fig. 2 is
`a histogram of the uumber of structures as a function of the
`donor : acceptor ratio (d/a). Thcrc arc hardly any structures
`where d/a is greater than unity but this is not surprising; fi’om
`the definitions of donor and acceptor used here, only a few
`types of compounds such as 1° amines and some of their
`derivatives would be expected to have d > a. The vast majority
`of hydrogen bonded compounds (hydrated or otherwise)
`would probably have d/a ratios in the range 0.5-3_.0. What is
`significant, however, is that 65% of the hydrated structures
`have d/a <0.5 with 16% of them having d/a <0,1. In many of
`these hydrates therefore, the number of hydrogen bond donor
`groups is far less than the number of acceptors, There are a
`number of reasons why such a correlation should be indistinct:
`the existence of three-centre bonds; the possibility of water
`hydrogen bonding to itself rather than to the organic
`compound and water performing a space-filling role within the
`lattice of an awkwardly-shaped molecule. Indeed all these
`situations were encountered among the 400-odd structures
`
`]" Structures were selected if they appeared in any of the following
`journals: J, Chem. Soc. (all sections); Ac~a Chem. Scan&; Acta
`Crys~allogr, (prior ~o bifurcation); Angew. Chem.; Bull. Chem. Soc.
`Jpn.; J, Chem. Phys,; J. Am. Chem. Soc.; J. Org. Chem.; Tetra-
`hedron; Tetrahedron Lett.
`
`Lupin Ex. 1005 (Page 5 of 6)
`
`

`
`428
`
`examined and water seems to occur in organic cyrstals in many
`ways.11.12 Other factors are probably also important: several
`categories of compounds containing only acceptor groups
`(nitrohydrocarbons, ethers, esters) perhaps do not crystallise
`as hydrates because o[ their very low water solubility. What is
`amazing is that in spite of these reasonable alternative
`possibilities, the correlation is as pronounced as is observed
`here.
`I thank G. Sirisha for enumerating the donor and acceptor
`groups [or the compounds in this study.
`
`Received, 1st October 1990; Corn 0/04418K
`
`References
`1 G. R. Desiraiu, in Crystal Engineering. The Design of Organic
`Solids, Elsevier, Amsterdam, 1989.
`
`CHEM. SOC., CHEM. COMMUN., I99I
`
`2 G. R. Desiraju and A. Gavezzotti, J. Chem. Soc., Chem.
`Commun., 1989, 621,
`3 G. R. Desiraju and A. Gavezzotti, Acta Crystallogr., Sect. B,
`1989, 45,473,
`4 A. Gavezzotti, J, Am. Chem. Soc., 1989, 111, 1835.
`5 M. C. Etter, Ace. Chem. Res., 1990, :~3,120.
`6 F. H, Allen, S. Bellard, M. C. Briee, B. A. Cartwright, A.
`Doubleday, H, Higgs, T. Hummelink, B. G. Hummelink-Peters,
`O. Kennard, W. D. S. Motherwell, J. R. Rodgers and D, G.
`Watson, Acta Crystallogr., Sect. B, 1979, 35, 2331.
`7 G. R, Dg~iraju and R. L. Harlow, unpublished results.
`8 L. Leiser0witz, Aeta Crystallogr., Sect. B, 1976, 32, 775.
`9 R. Parthasarathy, Acta Crystallogr,, Sect. B, 1969, ZS, 509.
`10 F. Shafiee, K. J. Haller and R. West, J. Am. Chem. Sot., 1986,
`1118, 5478.
`11 R. Parthasarathy, S. Chaturvedi and K. Go, Proc. Natl. Acad. Sci.
`USA, 1990, 87,871.
`12 H. L. Carrell, D. E. Zacharias, J. P. Glusker, R. C. Moschel,
`W. R. Hudgins and A. Dipple, Carcinogenesis, 1982, 3,641.
`
`A Short Step Synthesis of Optically Active myo-lnositol l~3,4,5-Tetrakis(phosphate)
`and myo-!nositol 1,4,5-Tris(phosphate) from 1,3,5-Tri-O-benzoyl-myo-inositol
`Yutaka Watanabe,* Takahiro Fujimoto, Tomoichi Shinohara and Shoichiro Ozaki*
`Department of Resources Chemistry, Faculty of Engineering, Eh~rne University, Matsuyama 790, Japan
`
`A short and, practical synthesis of myo-inositol 1,3,4,5-tetrakis(phosphate) and myo-inositol 1,4,5-tris(phosphatel has
`been achieved by direct benzoylation of myo-inositol, enantioselective tartaroylation and removal of acy protecting
`groups with Grignard reagents,
`
`Recently, there have been many reports~ on the synthesis of
`rnyo-inositol 1,3,4,5-tetrakis(phosphate) (IPa, 1) and rnyo-
`inositol 1,4,5-tris(phosphate) (IP~, 2), which are metabolites
`in the phosphoinositide cycle concerning a new intracellular
`signal transduction system.a Chemical synthesis of racemic IP~
`has been achieved in six or seven steps by several groups,
`whereas the synthesis of optically active IP4 took 10 to 13
`steps. This difference is attributed partly to the tedious
`derivatisation steps needed to form diastereoisomers, their
`separation, and removal of the chiral auxiliary. These facts
`have prevented a practical synthesis of optically acuve IPa.
`Recently, we have found an efficient method for obtaining
`optically active inositol derivatives based on an enantioselec-
`tive acylation using a tartaric acid monoester3 instead of
`optical resolution. Coupling this methodology with a straight-
`forward protection of the starting rnyo-inositol.4 a short and
`practical synthesis of IPa has now bccn found. Optically active
`IP3 has been also prepared concisely from the same synthetic
`intermediate. In this communication, these results are de-
`scribed.
`Benzoylation of myo-inositol 3 with benzoyl chloride (2.5
`equiv.) in pyridinc at 90 ~C readily yielded isolablc symmet-
`rical 1,3,5-tri-O-benzoyl-rn3 o-inositol 4:~ the benzoate could
`
`OFI2
`
`OR~
`
`’
`
`R’=R2=H
`~;; R, = Bz, R2 = H
`
`~ ---~O-.sCO2Me
`
`OH
`
`RO .,~..OpOaH2
`
`H2OaPO’"y’"OH
`OPO~H2
`
`1; R = PO3H2
`2; R= H
`
`OR
`
`OBz
`
`~671R=SiEta
`
`(R’CO = tartaroyl)
`
`O$iEta
`
`HO""
`
`""OSiEt3
`
`OH
`
`8;R=H
`11;R=Bz
`
`OSiEt3
`
`R~O"°° y ""OSiEI~
`OR1
`
`10; R
`
`O~
`12; R1 =~I~’--oFP(O)’ R2= Bz
`
`t myo-Inositol (3;0 g), benzoyl chloride (3.9 ml) and anhydrous
`pyridine (100 ml) were stirred together at 90 °C for 1 h; conventional
`work-up and flash chromatography (SiO~, AcOEt : CH~CIa, 1 : 6) gave
`4 (1.2 g) in 15% yield, R~ 0.3 (AcOEt : CHiCle, 1 : 6), m.p. 133 5 °C
`(from benzene).
`
`Scheme 1 Reagents and conditions: i, BzC1 (2.5 equiv,), pyridine; ii, 5,
`MsC1, N-methylmorpholine, dimethylaminopyrldine, tetrahydro-
`furan; tti, Et3SiC1, ilnidazole, dimethylformamide; iv, EtMgBr (for
`8), McMgBr (for 11), EtzO; v, 9, tetrazole, CH2Clz, then m~chloro~
`perbenzoic acid; Bz = PhCO; Ms = MeSO~
`
`Lupin Ex. 1005 (Page 6 of 6)