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A very effective strategy has been devised for the synthesis of 3-substituted pyrroles based on the use of the triisopropylsilyl (TIPS) moiety as a sterically demanding nitrogen substituent to obstruct the attack of electrophilic reagents at the a positions. 1 -(Triisopropylsilyl) pyrrole (1) undergoes highly preferential kinetic electrophilic substitution at the ß position with a variety of electrophiles (Br+, I+, N02+, RCO+, etc.) and fluoride ion induced desilylation of the products provides the corresponding 3-substituted pyrroles in good overall yields. Competitive trifluoroacetylation experiments demonstrate that substitution of TIPS-pyrrole at the a positions is decelerated by a factor of >104, vs pyrrole at the same sites, without affecting reactivity at the ß positions. l-(Triisopropylsilyl)-3-bromopyrrole ( 2) is readily converted into the 3-lithio compound 44 by bromine-lithium interchange with alkyllithium reagents. This previously unavailable, formal equivalent of 3-lithiopyrrole is itself an excellent source of a wide range of /3-substituted pyrroles, many of which would not be directly preparable from 1.TIPS-pyrrole can be 3,4-dihalogenated and these compounds undergo sequential halogen-metal interchange trapping reactions. This process is exemplified by an efficient, three-step synthesis of the antibiotic verrucarin E (63) from the dibromo compound 5. * Contribution no. 792.

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Driving innovation and creativity has relied heavily on new information technologies in the last decade. Human capital has certainly had its importance, but how to coordinate human capital in order to push productivity in research and development without compromising individual initiative is still not well understood. In this paper, we provide results showing that geometry of workspace has indeed an impact on communication patterns and may thus be used as a means to drive both innovation and efficient research. In order to be creative, new knowledge has to be created. Communication facilitates knowledge creation. We try to close the bridge between areas of creation of tacit knowledge and transfer of knowledge highlighted by authors like Nonaka, Takeuchi, Konno, von Krogh and von Hippel with the area of communication patterns pioneered by Allen, Hatch, and Stryker, by considering face-to-face (FTF) communication as a first step for socialization, socialization as a means for knowledge creation. In this article, we compare two different office environments within the same site, same activity, same hierarchical level and same company: a traditional cell office area and a new multi-space office, used by people who used to work in cell offices. We observed FTF communication patterns during 120 h in two areas and measured over 2,000 communication events. We found that people communicate three times more often in a multi-space area than in a cell-space area. We also found that the mean duration of communication events decreased from 9 to 3 min when transferring collaborators from a cell-space to a multi-space. Finally time spent without communication increased from 5% to 29% when going from cell-offices to multi-space areasleaving more time for people to work and think on their own. And we found that most communication events during work time in the multi-space took place at the work place and seldom or never in soft sitting areas installed for the purpose of communication.

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Enantiomerically pure cis-and trans-5-alkyl-l-benzoyl-2-(tert-butyl)-~~-methylimidazolidin-4-ones (1, 2, 11, 15, 16) and trans-2-(terf-butyl)-3-methyl-5-phenylimidazolidin-4-one (20). readily available from (S)-alanine, (S)-valine, (S)-methionine, and (R)-phenylglycine are deprotonated to chiral enolates (cf. 3, 4, 12, 21). Diastereoselective alkylation of these enolates to 5,5-dialkyl-or 5-alkyl-5-arylimidazolidinones (5, 6, 9, 10, 13a-d, 17, 18, 22) and hydrolysis give a-alkyl-a-amino acids such as (R)and (S)-a-methyldopa (7 and 8a, resp.), (S)-amethylvaline (14) and (R)-a-methyl-methionine (19). The configuration of the products is proved by chemical correlation and by NOE 'H-NMR measurements (see 23, 24). In the overall process, a simple, enantiomerically pure a-amino acid can be a-alkylated with retention or with inversion of configuration through pivalaldehyde acetal derivatives. Since no chiral auxiliary is required, the process is coined 'self-reproduction of a center of chirality'. The method is compared with other a-alkylations of amino acids occurring without racemization. The importance of enantiomerically pure, a-branched a-amino acids as synthetic intermediates and for the preparation of bio~ogicdl~y active compounds is discussed.In [l], we have shown that simple amino acids such as (S)-alanine, (S)-valine, (R)-phenylglycine, (S)-phenylalanine, and (S)-methionine can be converted selectively to imidazolidinones such as 1 and 2 of either cis-or trans-configuration. We now show that these imidazolidinones are deprotonated to synthetically useful chiral enolates.A) Reactions of the Chiral Imidazolidinone Enolates with Electrophiles. -As a first example, the preparation of ( R ) -or (S)-a -methyldopa ( =I 2-amino-2-methyl-3-(3,4-di-hydroxypheny1)propionic acid) from (S)-alanine is described (Scheme I). Solutions of the imidazolidinones (1 or 2) in THF were treated at dry-ice temperature with a slight excess of lithium diisopropylamide (LDA). Bright orange-red-colored solutions of the enantiomeric enolates (3, 4) were formed, which were combined with 3,4-dimethoxybenzyl bromide. Rapid decolorization indicated the progress of the alkylation step furnishing the enantiomeric 5,5-disubstituted imidazolidinones (5, 6, ca. 60 YO). We did not detect more than one diastereoisomer by HPLC of the crude products. Within experimental error, the two isomers 5 and 6 had identical physical properties such as melting points, IR, and NMR spectra, but an opposite sense of specific rotation.The heterocyclic ring and the phenolic methyl-ether groups of the enantiomer 6 were cleaved by heating for 4 hours in 6~ HC1 at 180" in a sealed tube. Isolation of the a-methyldopa thus produced caused considerable problems due to the known [2a] sen-') 2,Part of the projected Ph. D. theses of J.

Strong bases (lithium diisopropylamide (LDA) or BuLi) convert cyclosporin A (CS) to a hexalithio derivative containing a Li alkoxide, four Li azaenolate, and one Li enolate units. The Li, compound is solubilized in tetrahydrofuran (THF) by addition of excess LDA or LiC1. Reactions with electrophiles (alkyl halides, aldehydes, CICO,R, C02, (RS),, D,O) at low temperatures give products containing new side chains in amino-acid residue 3 of the cyclic undecapeptide (see 1-13, Schemes I and 2, and Figx. I and 2) in moderate to high yields and, with Reor Si-selectivities, depending upon the conditions of lithiation of up to 7: 1. Pure CS derivatives (Scheme 2, Table I