ALBERT

Notes: On acid-catalyzed hydrolysis, the tricyclic compounds 2 and 10, incorporating cyclopropyl-silyl-ether moieties undergo rearrangement to the cis-decalones 3 and 7, respectively. Hydrolysis of 2 and 10 in the presence of oxygen leads additionally to the formation of the 1,2-dioxolan-3-ols 9 and 13, respectively, which involves an electron-transfer oxygenation process as could be demonstrated by photooxygenation of the silyl ether 10 and the cyclopropanol 14 in the presence of 9,10-dicyanoanthracene. The configurations of 3 and 9 were assigned by X-ray analysis of the latter compound as well as of the p-nitrobenzoate 8 of 3.

Notes: The synthesis and photolysis of the title compound 3 is described. Irradiation (λ 〉 280 nm, MeCN) of the di-epoxyketone 3 leads predominantly to γ-H abstraction. Cyclization furnishes the cyclobutanols 22-24, while cleavage gives compound 25, presumably via the allene-oxide intermediate 36. Further, products 27 and 28 are formed by Norrish fragmentation and by initial cleavage of the C(α)—O bond of the oxirane, respectively. The structures of the products 22-25, 27, and 28 were assigned on the basis of the spectral data of the photolysis products of the 13C-labelled diepoxyketone[6,6-dimethyl-13C2]-3 and by X-ray analysis of the compounds 24 and 35, the latter being the p-nitrobenzoate of 22.

Notes: The titanates derived from α,α,α′,α′-tetraaryl-1,3-dioxolane-4,5-dimethanols (TADDOLs, prepared from tartrate) act as catalysts for enantioselective additions of dialkylzinc compounds to aldehydes. For the standard reaction chosen for this investigation of the mechanism, the addition of diethylzinc to benzaldehyde, there is very little change of selectivity with different aryl substituents on the TADDOLate ligands (Tables 2-4, examples). With 0.02 to 0.2 equiv. of the chiral titanates, selectivities above 90% are observed only in the presence of excess tetraisopropyl titanate! According to NMR measurements (Fig. 2), the chiral bicyclic titanate and the achiral titanate do not react to give new species under these conditions. From experiments with different stoichiometries of the components, and with different achiral or chiral OR groups on the Ti-atom of the seven-membered ring titanate, it is concluded (i) that a single chiral titanate is involved in the product-forming step, (ii) that the bulky TADDOLate ligand renders the Ti-center catalytically more active than that of (i-PrO)4Ti, due to fast dynamics of ligand exchange on the sterically hindered Ti-center (Table 5, Fig. 3), and (iii) that the role of excess (i-PrO)4Ti is to remove - by ligand exchange - the product alkoxides (R*O) from the catalytically active Ti-center (Scheme 4, Table 6). Three new crystal structures of TADDOL derivatives (two clathrates with secondary amines, and a dimethyl ether) have been determined by X-ray diffraction (Figs. 5-7), and are compared with those previously reported. The distances between the C(aryl)2O oxygen atoms in the C2- and C1-symmetrical structures vary from 2.58 to 2.94 Å, depending upon the conformation of their dioxolane rings and the presence or absence of an intramolecular H-bond (Fig. 8). A single-crystal X-ray structure of a spiro-titanate, with two TADDOLate ligands on the Ti-atom, is described (Fig. 9); it contains six different seven-membered titanate-ring conformations in the asymmetric unit (Fig. 10), which suggests a highly flexible solution structure. The structures of Ti TADDOLate complexes are compared with those of C2-symmetrical Ru, Rh, and Pd disphosphine chelates (Table 7). A common topological model is presented for all nucleophilic additions to aldehydes involving Ti TADDOLates (Si attack with (R,R)-derivatives, relative topicity unlike; Fig. 11). Possible structures of complexes containing bidentate substrates for Ti TADDOLate-mediated ene reactions and cycloadditions are proposed (Fig. 12). A simple six-membered ring chair-type arrangement of the atoms involved can be used to describe the result of TADDOLate-mediated nucleophilic additions to aldehydes and ketones, with Ti, Zr, Mg, or Al bearing the chiral ligand (Scheme 6). A proposal is also made for the geometry of the intermediate responsible for enantioselective hydrogenation of N-(acetylamino)cinnamate catalyzed by Rh complexes containing C2-symmetrical diphosphines (Fig. 13).

Notes: The substituted 1,2,3,4,4a,9,10,10a-octahydrophenanthrene-4,9-dione 2, synthesized from the cyclohexanone 8 and quinone 11 (Scheme 2), was found by X-ray analysis adn 1H-NMR studies to be the isomer with cis-junction of the saturated rings. The cis-fusion could also be determined from the 1H-NMR data of the related compound 17 (Scheme 4), which was previously considered to be trans-fused. In contrary to previous argumentations, the interaction of the C(4)-carbonyl O-atom of trans-fused octahydrophenanthenes is more severe with a 5-methoxy than with a 5-methyl substituent.

Notes: A variety of model compounds for the pyrimidinediyl-based rigid-rod polyamide poly[imino-(pyrimidine-2,5-diyl)-imino-tetraphthaloyl] (PPYMT) was prepared, in order to compare their conformations to several model compounds of the related, fully aromatic polymer poly(p-phenyleneterephthalamide) (PPTA). In particular, the structures of N-(2-pyrimidyl)benzamide (PYMB) and its complexed form bis[(N-pyrimidin-2-yl)benzamide]nickel(II) dichloride (NiPYMB) were determined by X-ray diffraction. The molecular packing in these crystals provides us with a model for the possible ‘cross-linking’ of PPYMT fibers. The structures of the trimer model compounds N,N′ -bis(2-pyrimidyl)terephthalamide (PYTA) and N,N′ -bis(benzoyl)-2,5-diaminopyrimidine (BDAP) yield information about the conformation of PPYMT chains and are compared to analogous model compounds of PPTA.

Notes: The isomers 6-methyl-2-propionyl- and 3-methyl-2-propionylbenzoic acid were synthesized and separated by DCC (droplet counter-current) chromatography. The crystal structure analyses showed that these compounds are hydroxylactones in the solid state.

Notes: The X-ray structures of fifteen 1, 3-imidazolidine, 1, 3-oxazolidine, 1, 3-dioxan-4-one, and hydropyrimidine-4(1H)-one derivatives are described (Table 2) and compared with known structures of similar compounds (Figs. 1-20). The differences between structures containing exocyclic N-acyl groups and those lacking this structural element arise from the A1,3 effect of the amide moieties. Even t-Bu groups are forced into axial positions of six-ring half-chair or into flag-pole positions of six-ring twist-boat conformers by this effect (Figs. 16-20). In the N-acylated five-membered heterocycles, a combination of ring strain and A1, 3 strain leads to strong pyramidalizations of the amide N-atoms (Table 1) such that the acyl groups wind up on one side and the other substituents on the opposite side of the rings (Figs. 4-9 and Scheme 3). Thus, the acyl (protecting!) groups strongly contribute to the steric bias between the two faces of the rings. Observed, at first glance surprizing stereoselectivities of reactions of these heterocycles (Schemes 1 and 2) are interpreted (Scheme 3) as an indirect consequence of the amide A1, 3 strain effect. The conclusions drawn are considered relvant for a better understanding of the ever increasing role which amide groups play in stereoselective syntheses.

Notes: Cyclic Oligomers of (R)-3-Hydroxybutanoic Acid: Preparation and Structural AspectsThe oligolides containing three to ten (R)-3-hydroxybutanoate (3-HB) units (12-through 40-membered rings 1-8) are prepared from the hydroxy acid itself, its methyl ester, its lactone (‘monolide’), or its polymer (poly(3-HB), mol. wt. ca. 106 Dalton) under three sets of conditions: (i) treatment of 3-HB (10) with 2,6-dichlorobenzoyl chloride/pyridine and macrolactonization under high dilution in toluene with 4-(dimethylamino)pyridine (Fig. 3); (ii) heating a solution (benzene, xylene) of the β-lactone 12 or of the methyl ester 13 from 3-HB with the tetraoxadistanna compound 11 as trans-esterification catalyst (Fig. 4); (iii) heating a mixture of poly(3-HB) and toluene-sulfonic acid in toluene/1,2-dichloroethane for prolonged periods of time at ca. 100° (Fig. 6). In all three cases, mixtures of oligolides are formed with the triolide 1 being the prevailing component (up to 50% yield) at higher temperatures and with longer reaction times (thermodynamic control, Figs. 3-6). Starting from rac-β-lactone rac-12, a separable 3:1 to 3:2 mixture of the l,u- and the l,l-triolide diasteroisomers rac-14 and rac-1, respectively, is obtained. An alternative method for the synthesis of the octolide 6 is also described: starting from the appropriate esters 15 and 17 and the benzyl ether 16 of 3-HB, linear dimer, tetramer, and octamer derivatives 18-23 are prepared, and the octamer 23 with free OH and CO2H group is cyclized (→6) under typical macrolactonization conditions (see Scheme). This ‘exponential fragment coupling protocol’ can be used to make higher linear oligomers as well. The oligolides 1-8 are isolated in pure form by vacuum distillation, chromatography, and crystallization, an important analytical tool for determining the composition of mixtures being 13C-NMR spectroscopy (each oligolide has a unique and characteristic chemical shift of the carbonyl C-atom, with the triolide 1 at lowest, the decolide 8 at highest field). The previously published X-ray crystal structures of triolide 1, pentolide 3, and hexolide 4 (two forms), as well as those of the l,u-triolide rac-14, of tetrolide ent-2, of heptolide 5, and of two modifications of octolide 6 described herein for the first time are compared with each other (Figs. 7-10 and 12-15, Tables 2 and 5-7) and with recently modelled structures (Tables 3 and 4, Fig. 11). The preferred dihedral angles τ1 to τ4 found along the backbone of the nine oligolide structures (the hexamer and the larger ones all have folded rings!) are mapped and statistically evaluated (Fig. 16, Tables 5-7). Due to the occurrence of two conformational minima of the dihedral angle O—CO—CH2—CH (τ3 = + 151 or -43°), it is possible to locate two types of building blocks for helices in the structures at hand: a right-handed 31 and a left-handed 21 helix; both have a ca. 6 Å pitch, but very different shapes and dispositions of the carbonyl groups (Fig. 17). The 21 helix thus constructed from the oligolide single-crystal data is essentially superimposable with the helix derived for the crystalline domains of poly(3-HB) from stretched-fiber X-ray diffraction studies. The absence of the unfavorable (E)-type arrangements around the OC—OR bond (‘cis-ester’) from all the structures of (3-HB) oligomers known so far suggests that the model proposed for a poly(3-HB)-containing ion channel (Fig. 2) must be modified.

Notes: The enolate generated from S-phenyl (S)-1-benzyl-2-azetidinecarbothioate is converted into racemic products 2 by treatment with electrophiles. The bicyclic oxazolidinone derivative 12 has been prepared from trimethylsilyl (S)-1-(trimethylsilyl)-2-azetidinecarboxylate (11) and pivalaldehyde without racemization. Addition of 12 to aldehydes and hydrolysis gives the products 13 a-h. The structure of the adduct 13 h from 4-pyridinecarbaldehyde was determined by X-ray crystal structure analysis, proving that the trigonal centers of the bicyclic enolate and of the aldehyde have combined with relative topicity unlike. Thus, the reaction resembles that of the homologous proline derivative described previously, and the novel products are formally D-allo-threonines with an ethylene bridge between the nitrogen and the adjacent carbon atoms (Scheme 4) and with absolute configuration R,R. The mechanism of the C — C bond-forming reaction is discussed.