João Alifantes

Evaluation of lipase from Candida rugosa in the resolution of endo-(±)-1,8,9,10,11,11-hexachloropentacyclo[6.2.1.13,6.02,7.05,9]dodecan-4-alcohol

Abstract endo -(±)-1,8,9,10,11,11-Hexachloropentacyclo[6.2.1.1 3,6 .0 2,7 .0 5,9 ]dodecan-4-ol (±)- 7 and exo -(±)-1,8,9,10,11,11-hexachloropentacyclo[6.2.1.1 3,6 .0 2,7 .0 5,9 ]dodecan-4-ol (±)- 4 have been prepared and the enantiomeric enrichment capacity of the lipase from Candida rugosa in the transesterification with vinyl acetate of these compounds was evaluated. It was verified that the lipase recognize only the alcohol (±)- 7 , producing endo -(+)-1,8,9,10,11,11-hexachloropentacyclo[6.2.1.1 3,6 .0 2,7 .0 5,9 ]dodecan-4-yl acetate (+)- 8 with ee >95% and conversion of 44% as the only product.

Structures of half-cage pentacyclododecane derivatives: skeletal deformations due to steric compression-decompression

Abstract Hexachlorinated half-cage isomer acetates may be obtained from isodrin in acetic acid under the proper conditions and separated in highly pure form. The X-ray crystal structure of the “inside” acetate shows that it is still more sterically congested than the previously reported “outside” one. Bond lengths and angles for both isomers reveal large deviations from those normally found in saturated systems providing interesting models for the investigation of steric effects on chemical bonding.

Skeletal and chlorine effects on 13C-NMR chemical shifts of chlorinated polycyclic systems

Com o objetivo de realizar uma analise comparativa do efeito de compressao anelar e do Cl no deslocamento quimico dos carbonos clorados tencionados, foram analisados os deslocamentos quimicos de 27 estruturas policiclicas cloradas e nao cloradas derivadas dos inseticidas “aldrin” (5) e “isodrin” (14). Os compostos foram divididos em quatro grupos de acordo com a conformacao e numero de aneis: tetraciclododecanos endo-exo, tetraciclododecanos endo-endo, pentaciclododecanos e hexaciclododecanos. A comparacao do deslocamento quimico de carbono-13 entre compostos clorados e nao-clorados mostrou que, quando C-9 e C-10 sao carbonos olefinicos, ocorre um deslocamento para baixa frequecia de 0.5-2.4 ppm para os tetraciclododecanos endo-endo e de 4.7-7.6 ppm para os tetraciclododecanos endo-exo. Para C-11, a variacao do deslocamento quimico atinge valores de 49-53 ppm para os tetraciclicos endo-exo e endo-endo, de 54 ppm para o pentaciclico e de 56-59 ppm para os hexaciclicos. A partir desses dados foi possivel observar a influencia da compressao anelar no deslocamento quimico. In order to establish a comparative analysis of chemical shifts caused by ring compression effects or by the presence of a chlorine atom on strained chlorinated carbons, a series of the chlorinated and dechlorinated polycyclic structures derived from “aldrin” (5) and “isodrin” (14) was studied. Compounds were classified in four different groups, according to their conformation and number of ring such as: endo-exo and endo-endo tetracyclics, pentacyclics and hexacyclics. The 13 C chemical shift comparison between the chlorinated and dechlorinated compounds showed that when C-9 and C-10 are olefinic carbons, it occurs a shielding of 0.5-2.4 ppm for endo-endo tetracyclics and of 4.7-7.6 ppm for endo-exo tetracyclic. The chemical shift variation for C-11 reaches 49-53 ppm for endo-exo and endo-endo tetracyclics, 54 ppm for pentacyclic and 56-59 ppm for hexacyclic compounds. From these data, it was possible to observe the influence of ring compression on the chemical shifts.

MOLECULAR STRUCTURE OF HALF-CAGE: X-RAY DIFFRACTION AND SEMIEMPIRICAL CALCULATIONS OF EXO-(±)-1, 8, 9, 10, 11, 11-HEXACHLOROPENTACYCLO [6.2.1.13,6.02,7.05,9]DODECAN-4-ALCOHOL

The crystal structure of exo-(±)-1, 8, 9, 10, 11, 11-hexachlorop-entacyclo-[6.2.1.13, 6.02, 7.05, 9]dodecan-4-alcohol (half-cage 1) was determined by a single crystal X-ray diffraction at 293 K. The crystal parameters of this compound are as follows: triclinic, space group P , a = 8.0709(9), b = 8.3721(9), and c =, 11.4812(9) Å, α = 86.571(8)º β = 87.360(8)º γ = 62.815(10)º R = 3.28% and wR 2 = 8.01%. MNDO-PM3, AM1, and MNDO semiempirical methods were performed to establish one comparison between X-ray and theoretical data in order to verify what theoretical method calculations best reflect the molecular structure.

Ab initio and density functional study of the 5-pentacyclo[6.2.1.13.6.02.7.04,10]dodecyl cation. A symmetrical μ-hydride bridged carbocation

Abstract MP2/6-31g(d,p) and B3LYP/6-31g(d,p) calculations for the pentacyclo[6.2.1.1 3,6 .0 2,7 .0 4,10 ]dodecyl cation reveal two minima on the potential energy surface. The most stable minimum is the μ-hydride bridged cation 2 . The second minimum is the two-electron three-center bonded structure 3 . At MP2/6-31g(d,p) 2 is only 0.2 kcal/mol more stable than 3 , but at B3LYP/6-31g(d,p) this energy difference increases to 3.3 kcal/mol. The energy difference between 2 and 3 is only 3.8 kcal/mol. Solvent effect does not affect these numbers significantly. This low energy barrier may account for the product distribution observed on solvolysis of pentacyclic derivatives.

Asymmetric synthesis of half-cage alcohol compounds

Abstract To obtain enantiopure pentacyclic chlorinated and dechlorinated alcohols, we evaluated various synthetic routes. Enantiopure acetate (−)-5 (ee >95%) was obtained from an enantioselective inversion of a stereogenic center of the pentacyclic acetate (+)-4 in an acidic medium. Conversely, enantiopure alcohols (+)-11 and (+)-15 were obtained by the kinetic resolution of alcohol (±)-11 by transesterification using lipase from Candida rugosa. It was verified that the lipase recognized alcohol (±)-11, producing the alcohol (+)-11 (ee >98%) and acetate (−)-13 (ee >99%) with a high degree of enantioselectivity (E >100) and a conversion of 50% after only 1 h.

Study of the kinetic resolution of (′)-10-exo-hydroxy-pentacyclo[6.2.1.13,6.02,7.05,9]dodeca-4-one by lipase catalysis and the intramolecular racemization of the pure enantiomer by thermal dyotropic reaction

Abstract In this work, the modified synthesis of (±)-10- exo -hydroxy-pentacyclo[6.2.1.1 3,6 .0 2,7 .0 5,9 ]dodeca-4-one (±)- 10 as well as its resolution by lipase-catalyzed transesterification with vinyl acetate is described. A thermal racemization process of (+)- 10 to (±)- 10 was observed. A mechanism involving racemization of (+)- 10 through dyotropic intramolecular hydrogen migration is proposed and supported by computational analysis.

Co-crystallization of pentacyclododecane acetate rotamers of opposite chirality: effects of steric interactions and negative hyperconjugation on molecular structure

Abstract Under proper conditions, half-cage isomers of systems that have been used as model compounds in a number of studies on structure and reactivity may be obtained and separated in highly pure form. Comparison of the X-ray crystal structures of ‘inside’ and ‘outside’ hexachlorinated acetates reveals that while the inside acetates give rise to single-crystals of a unique optical isomer, two conformers of the outside compound with opposite chirality crystallize together in a centrosymmetric space group. As predicted by ab initio calculations of these systems, they correspond to minima for rotational isomers for which factors such as steric interactions and negative hyperconjugation may account for the observed differences in bond lengths and angles. Association of chiral forms of the outside isomer may be responsible for the difference in its response to enzymatic conversion as compared to that of the inside isomer.

Use of chiral lanthanide shift reagents in the elucidation of NMR signals from enantiomeric mixtures of polycyclic compounds

1 H and 13C NMR is used to study the effects on a set of racemic polycyclic compounds of the application of the chiral shift reagents europium(III) tris[3-(trifluoromethylhydroxymethylene)-(+)-camphorate] and europium(III) tris[3-(heptafluoropropylhydroxymethylene)-(+)-camphorate]. The study compares the chiral shift reagents to find the conditions resulting in optimum enantiomeric (ΔΔδ) and spectral resolution (Δδ). Of the two reagents Eu(hfc)3 proved to be the more efficient. In addition, the effect of the achiral lanthanide shift reagent Eu(fod)3, used in combination with the chiral lanthanide shift reagents, was investigated.

On the mechanism of skeletal rearrangements in the acid catalysed acetylation of isodrin

1,8,9,10,11,11-Hexachlorotetracyclo[6.2.1.13,6.02,7]dodec-9-en-4-exo-yl acetate, tetracyclic1; 1,2,2,3,10,11-hexachloropentacyclo[5.4.1.03,10.04,12.05,9]dodecan-8-exo-yl acetate, half-cage2; 1,2,2,3,10,11-hexachloropentacyclo[5.4.1.03,10.04,12.05,9]dodecan-8-endo-yl acetate, half-cage3 and 1,9,10,11,11,12-hexachlorohexacyclo[5.4.1.02,6.03,10.04,8.09,12]dodecane, birdcage4 were obtained from acid catalysed acetylation of isodrin. It was observed that the intramolecular rearrangement control is highly dependent on reaction time. The equilibria involved in these rearrangements were determined by gas chromatography. Semiempirical calculations at the PM3-MNDO, AM1 and MNDO levels have been performed to obtain the optimized geometry of the reagent, products, intermediates and transition states for the rearrangement mechanism. The results of the calculations are in good agreement with the experimental data. On the basis of the theoretical and experimental investigations we propose a revised mechanism which involves a new transition state and a new non-classical reaction intermediate.