ALBERT

Notes: (R,S)-N-Acetyl-leucine-2-naphthylamide can be resolved into its enantiomers on a (S)-DNBLeucine chiral stationary phase. The mechanism of this separation was investigated using as model complexes the 1:1 S,S- and the 1:1 R,S-cocrystals of the above naphthylamide and N-3,5-dinitrobenzoylleucinemethylamide, a soluble analogue of the stationary phase. The observed enantiomeric elution order can be rationalized from their X-ray data.

Notes: The propensity of the N=N bond to undergo photo [2 + 2] cycloadditions has been further explored. In the specifically designed 1,5-azo/enes 1-3, no [2 + 2] cycloaddition has been observed upon either direct or sensitized excitation with light of various wave lengths at temperatures down to 77 K, in line with expectations based on X-ray (1: d = 2.71 Å, ω = 129°) and PE measurements (1: I1 = 8.00, I2 = 9.05 eV; 2; I1 = 8.00, I2 = 9.25eV). The steric/stereoelectronic demands for the participation of the N=N bond in pericyclic reactions are clearly more stringent than those for the C=C bond.

Notes: The original suggestion that a through-space mechanism was operative in the seven-bond J(P, P) coupling constant of 30.3 Hz observed for 3.3′-bis(1,1-dimethylethyl)-2,2′-[3,3′,5,5′-tetrakis(1,1-dimethylethyl)-1,1′-biphenyl-2,2′-diyl]bis(oxy)}bis[1,3,2-oxazaphospholidine] (1a)) was investigated. In the solid-state CP-MAS 31PNMR spectrum of 1a, two nonequivalent P-atoms were observed; sufficient resolution could not be obtained to determine whether P, P coupling was present. The preparation and spectral data of the N-methyl analogue 1b and of the acyclic N-isopropyl analogue 6 (Scheme 1) provided evidence that a) the essentially exclusive formation (R*, R*,S*)-1ain the reaction of the disodium biphenyldiolate 3a with the phosphorochloridite 4a is the result of significant differences in the free energy of activation (ΔG*) for the formation of the various diastereoisomers due to the steric congestion within the molecule and that b) the magnitude of the observed P,P coupling is dependent upon the degree of conformational freedom within the molecule. In the 31P-NMR spectrum of the P-sulfide 7, which was prepared by the reaction of la with sulfur, 2s resonances were observed that strongly suggested that the lone electrons pair on P are involved in the mechanism for the transmission of coupling data. The (4S,5R)-12 and (4R, 5S)-12 of la were prepared in a three-step reaction sequence starting from the corresponding enantiomerically pure norephredine 8 (Scheme 2). Both (4S, 5R)- and (4R, 5S)-12 were obtained as a diastereoisomer mixture that differ by the configuration of the axis of chirality, i.e., (R*R*,R*)- and (R*,S*,R*)-12 were obtained. The major diastereoisomer was obtained upon recrystallization, and the atropisomers were observed to equilibrate in solution by monitoring the H—C(5) resonance in the 1H-NMR with time (ΔG° = 0.4 kcal/mol; Fig. 2). The process observed corresponds to the restricted rotation about the central single bond of the biphenyl system. The isolation of an atropisomer with only a single ortho substituent on each aryl ring is quite rare. In the 13C-NMR spectrum of both (R*,R*,R*)- and (R*,S*,R*)-12, C(5) is two-bond-coupled to the oxazaphospholidine P-atom (2J(C(5),P((2)) = 8.5 Hz) that is further virtually coupled to the P-atom of the other oxazaphospholidine ring (7J(P(2),P(2′)) = 30 Hz; 9J(C(5),P(2′)) = 0 Hz; δ(P(2)) = δ(P(2′)) = 136 ppm. In the 31P-NMR spectrum of (R*,R*,S*)-12, which was prepared from the racemic chloridite (mixture of three diastereoisomers was obtained), a 7J(P(2),P(2′) of 36 Hz was observed. These observations provide strong evidence that seven-bond P,P coupling occurs in all three diastereoisomers of 12. The observed P,P coupling is both independent of the configuration of the chiral axis and the configuration of the asymmetric P-centers. This independence of P,P coupling upon the configuration on P implies also the independence of the observed coupling upon the orientation of the lone-pair of electrons on P provided that the conformations of the diastereoisomers are similar in solution. The X-ray crystal structure of the complex formed from 1a and dichloro(cycloocta-1,5-diene)platinum(II) was obtained and the solid-state structure discussed. The major diastereoisomer of (4S,5R)-12 was used as a chiral ligand in asymmetric hydrosilylation and hydrogenation reactions (Scheme 3).

Notes: Formation of two unknown, tricyclic trimers of diketene, 3 and 4, was observed in diketene solutions containing (CH3)3SiCl/NaI or TsOH.

Notes: Derivatives of the unknown 2-amino-6H-1,3-oxazin-6-one 2 have been synthesized for the first time in two steps and in excellent yields, starting from N-cyanocarbonimidates 3a-c and cyanoacetates. The structures of 2a-c are assigned by NMR-spectroscopic methods and corroborated by an X-ray structure analysis of 2c.

Notes: Bimetallic inclusion complexes have been synthesized by a secondary coordination interaction between the guest complex [Fe(η5-C5H5)(CO)2(NH3)][PF6] and copper(II) complex 1a or nickel(II) complex lb containing crown-ether hosts. The X-ray crystal-structure analysis established that the Cu,Fe inclusion complex 2 crystallize as a centrosymmetric dimer with a Cu—Cu separation of 3.73 Å and a novel out-of-plane Cu—N interaction. The magnetic parameters for 2 were obtained by ESR and ENDOR spectroscopy. ESR susceptibility measurements down to 6 K exclude the presence of any antiferromagnetic coupling interaction between the CuIIcenters of the dimer.

Notes: Thermolysis of steroidal 5α, 8α- peroxides of type 3a-d generates as major products the corresponding diseco compounds containing a 14-membered ring instead of the standard A-B-C-ring skeleton. Depending on the reaction conditions, either the primary products of type 9 or the α, β-unsaturated ketones of type 4, formed by subsequent elimination of AcOH, are isolated. The latter, configurationally uniform compounds undergo epoxidation of the C(9)=C(10) bond followed by a Baeyer-Villiger oxidation to give, as final products, the 15-membered cyclic epoxyenol lactones of type 20 and 21. The structures of the various products were determined by 1H- and 13C-NMR spectroscopy. The conformations of the 14- and 15-membered rings were established by X-ray structure analyses of 7 and 21a. A reaction mechanism for the above transformations is discussed.

Notes: The thermolysis of the steroidal 5α,8β-peroxide 1, under acidic conditions afforded in addition to the expected 5,10:8,9-diseco derivative 2, the rearranged 5α,8β-epoxide 3, the structure of which was determined by NMR spectroscopy and X-ray analysis.

Notes: Synthesis of an Optically Active Penem Intermediate by Asymmetric AmidoalkylationThe amidoalkylation of an optically active, cationic glycine derivative with methyl acetoacetate furnishes an intermediate 10a (Scheme 2) that is transformed in six steps to the optically active, silyl-protected 4-acetoxy-3-(1-hydroxyenthyl)-2-azetidinon 18a, a well known intermediate in penem synthesis.

Notes: The enantioselective copper-catalyzed 1,4-addition of Grignard reagents to α,β-unsaturated carbonyl compounds was studied with the following CuI compounds as catalyst precursor and 1,2:5,6-di-O-isopropylidene-3-thio-α-D-glucofuranose (Hsiig) as chiral ligand: CuI, iodo[bis(dibutylsulfide)]copper(I), [Cu(siig)], [Cu(siig)(pp)] (pp =1,2-bis)(diphenylphosphinoethene), and tetrakis[iodo(tributylphosphine)]copper(I). The addition of BuMg halides to cyclohex-2-en-1-one was tested under several reaction conditions. The chemical yields and regioselectivities for this reaction were, in all cases, larger than 90 and 98%, respectively, and independent of the experimental conditions. The enantioselectivity was strongly dependent on the reaction conditions and reached a maximum of 60%. Several other substrates were also tested in the above reaction. The X-ray crystal structure for [Cu(siig)(pp)] was determined by X-ray crystallography.