Jorma Mattinen

Stereochemical studies 130 saturated heterocycles 132: Synthesis and ring-chain tautomerism of stereoisomeric 1,3-oxazines condensed with the cyclopentane ring

Abstract Through condensation of cis -2-hydroxymethylcyclopentylamine ( 3 ) and cis -2-amintimethylcyclopentanol ( 5 ) with aromatic aldenydes, tautomeric mixtures of 1,3-oxazines and open-chain Schift bases were obtained. The two series of compounds ( 4a - f , 6a - f ) gave satisfactory linear correlations corresponding to log Kx = kσ+ + log Kx=w(k = 0.76 ±0.04 as shown earlier2). The ring form of the corresponding trans derivatives is present in a fairly low amount, because of the strain in the trans fusion of the cyclopentane and the six-membered hetero ring. N -Methyl substitution makes the ring form in the latter compounds stable, resulting in oxazines 12 and 14 . All the cyclizations in question occurred stereospecifically.

A new aspect of the leuckart reaction: Synthesis of 1-methyl and/or 3-hydroxymethyl-1,3-heterocycles

Abstract Cis - and trans -1-methyl-3-hydroxymethyl- and 1,3-dimethylperhydroquinazolinones ( 3a , b , 4a , b ) and-hydroxymethyl-1,3-perhydrobenzoxazinones ( 6a , b ) were synthesized by using a formaldehyde-formic acid mixture for reductive methylation, condensation and hydroxymethylation.

Conformational Analysis. 30-A1H and13C NMR Stereochemical Study onN-Methyl-Substitutedcis- andtrans-Fused Octahydro-2H-1,3- and -3,1-benzoxazines

The 1H and 13C NMR spectra of cis‐ and trans‐fused N‐methyloctahydro‐2H‐1,3‐ and ‐3,1‐benzoxazines and their 2‐methyl derivatives were analysed. All trans‐fused derivatives studied existed in biased double chair conformations with roughly equal contributions of the equatorial and axial N‐methyl groups. Of the cis‐fused isomers, both N‐methyl‐octahydro‐2H‐1,3‐benzoxazine and its 2‐methyl derivative attain exclusively the O‐in conformation, whereas N‐methyloctahydro‐2H‐3,1‐benzoxazine is not conformationally homogeneous but a ca. 3:1 mixture of the N‐in and N‐out forms at 198 K and a 7:3 mixture at ambient temperature. Similarly, the 2‐methyl derivative of N‐methyloctahydro‐2H‐3,1‐benzoxazine was found to be a ca. 3:2 mixture of C‐2 epimers with the N‐in and N‐out conformations, respectively.

Saturated heterocycles, 1371. Synthesis and steric structure of stereoisomeric 2-p-nitrophenylperhydroquinazolin-4-ones

Abstract Ethyl cis - and trans -2-aminocyclohexanecarboxylate (4) were used as starting material to prepare ( r -4a, t -2,_ t -8a)-, ( r -4a, c -2, c -8a)- and ( r -4a, t -2, c -8a)-2-p-nitrophenylperhydroquinazol-in-4-one and their 3-methyl-substituted derivatives in stereospecific or stereoselectlve syntheses. The relative configurations of the quinazolones were assigned via DNOE measurements. Crystal structure determinations of cis - 7a and cis - 8a were also performed by X-ray diffraction.

Kinetics and mechanism of tetrazole-catalyzed phosphoramidite alcoholysis

Kinetics of the tetrazole-catalyzed reaction of diisopropyl N,N-diisopropylphosphoramidite (1b) with tert-butyl alcohol has been studied by 31P NMR spectroscopy in THF, and the results obtained have been compared to those observed for the possible partial reactions involved, viz. the formation of diisopropyl tetrazolylphosphite (2b) and its subsequent alcoholysis. The stoichiometry of the processes was first examined with dimethyl N,N-diisopropylphosphoramidite (1a) in MeCN. The tetrazole-promoted disappearance of 1b is as fast in the absence and in the presence of the alcohol: the alcoholysis of 1b is zero-order in the concentration of alcohol and second-order in the concentration of tetrazole. The reaction of 1b with tetrazole is independent of the concentration of the tetrazolide anion and second-order in that of tetrazole, while the reverse reaction, aminolysis of 2b is first-order in the concentration of the amine. The alcoholysis of 2b is, in turn, first-order in the concentration of alcohol and second-order in that of tetrazole, but it also proceeds, although slowly, in the absence of tetrazole. The time-dependent product distribution of the alcoholysis of 1b shows intermediary accumulation of 2b, but at a lower level than could be predicted by applying the rate constants determined independently for the assumed partial reactions. Accordingly, tetrazole-catalyzed alcoholysis of 1b is shown to proceed at least mainly via 2b, but an additional pathway not involving 2b as an intermediate is proposed. Mechanisms of the partial reactions are discussed on the basis of the formal kinetics observed.

Multinuclear and 2D NMR structural study of methyl-substituted 1,3-dioxadecalanes

Abstract The configurations and conformations of 11 1,3-dioxadecalane derivatives were determined by multinuclear and 2D NMR spectroscopy. No conformational equilibria were found even in the 2,2-dimethyl substituted compound. In one case (9) only the O-out conformation prevails. The values of the methyl substituent effects on the 13C NMR chemical shifts of 1,3-dioxane were found useful in the present case, too. The 17O NMR chemical shifts were also helpful in both conformational and configurational assignments.

Direct NMR spectroscopic proof for the ring-chain tautomerism in the thiazolidine system

Abstract 2-(2′-Hydroxy-5′-bromophenyl)-benzothiazoline exists as a ring-chain tautomeric mixture in CDCl3 and DMSO-d6 as proved by NMR spectroscopy.

Stereochemical studies 136. saturated heterocycles 141.1 synthesis and conformational study of stereoisomeric 2,2-disubstituted-5,6-tri- and -5,6-tetramethylene-tetrahydro-1,3-oxazin-4-ones

Abstract Diastereomers of 2,2-disubstituted-5,6-tri- and 5,6-tetramethylenetetrahydro-1, 3-oxazin-4-ones ( 5a,b-12a,b ) were synthesized from cis-2-hydroxycyclopentane and -cyclohexanecarboxamides ( 3, 4 ) by condensing them with 2-butanone, 3-methyl-2-butanone, 3,3-dimethyl-2-butanone or acetophenone. The stereoselectivity of the ring closure depends on the steric requirements of the C-2 geminal substituents, although the predominant conformation ( o - in ) remains the same in both sets of the heterocycles.

Configurations and conformations of isomeric 3-methyl-2,4-dioxabicyclo [3.3.1]nonanes - their preparation and multinuclear and 2d nmr study

Abstract Both 3α- ( 1 ) and 3 β-methyl-2,4-dioxabicyclo[3.3.1] nonanes ( 2 ) have been prepared and their configurations and conformations clarified with the aid of high-field 1H, 13C, and 17O NMR study. The β-isomer ( 2 ) was obtained by isomerizing the α-isomer ( 1 ) on Kieselguhr in the gas phase. At 400 MHz in C6D6 all of the 1H signals for 1 ,and 2 could be detected. For the assignment of the 1H and 13C signals heteronuclear shift correlated 2D measurements were used. The vicinal and several long-range coupling constants which were determined with the aid of homonuclear 1H-1H shift correlations (COSY) and several decoupling experiments allowed together with some NOE and ASIS effects as well as with some other NMR data the unambiguous deduction of the configurations and conformations of 1 and 2 .

Zur Stereoisomerie der 2,6-Dichlor-4-methoxyheptane

Abstract2,6-Dichloro-4-methoxy-heptanes may exist as 2 optical active isomers and 2 meso compounds. By double addition of α,α-dichloro-dimethylether to propene a mixture of these stereoisomers was obtained. They were separated by HPLC. Using1H- and13C-NMR-spectroscopy their configuration could be established.