Stereochemistry methoxylation

In a study of stereochemistry, the half ether (5) of an unsymmetrical diol (6) was required. There is little prospect of making (5) from (6) as chemoselectlvity presents a formidable problem. Grignard disconnection from the tertiary alcohol would leave o-methoxyl ketones (7) or (8). 

Oxostephasunoline (4) was isolated from the roots of Stephania japonica(4). The UV spectrum of oxostephasunoline (4) showed an absorption maximum at 286 nm, and the IR spectrum depicted bands at 3550,3500, and 1670 cm, indicating the presence of a hydroxyl group and a y-lactam. The mass spectrum (Table VI) exhibited the most abundant ion peak at m/z 258, and the H-NMR spectrum (Table II) revealed the presence of three methoxyl and one N-methyl group. The downfield shift (53.06) of the JV-methyl resonance indicated that oxostephasunoline (4) was a y-lactam, which was further supported by the IR band at 1670 cm 1, significant features of the mass spectrum (Table VI), and the 13C-NMR spectrum (Table III). On exhaustive H-NMR analysis similar to the case of stephasunoline (17), the structure of oxostephasunoline (4) including the stereochemistry was practically proved (4). 

The reaction of phenyl-substituted alkenes (2-phenylprop-l-ene, ( )-l-phenylprop-l-ene, 1,1-diphenylethene, 1,1-diphenylprop-l-ene) with F-Teda BF4 (6) in the presence of various alcohols results in the formation of vicinal fluoro alkoxy adducts with Markovnikov-type regioselec-tivity.89,94 The stereochemistry of the fluorination-methoxylation addition reaction is slightly syn predominant in the case of (Z)-stilbene, indene, and dibenzosuberenone, while equal amounts of both diastereoisomers are formed in the case of ( )-l-phenylprop-l-ene and acenaphthylene. 

In the H NMR spectrum of haplophytine 1454] the C(16) methoxyl group protons absorb at unusually low frequency (8 3-00) and the 11 -protons at 8 6-27. The 11 -proton is shielded by the aspidophytine aromatic ring and the 16-methoxyl protons by the haplophytine aromatic ring in the preferred conformation of the molecule. (273) Additional examples of variations in H NMR parameters with stereochemistry are provided by the spectra of the compounds [460]-[468]. In the vindolinine derivatives [460]—[463] (279) the pair of compounds [460] and [461] show the influence of the aromatic ring on... 

The stereochemistry at C-3 in the 1,6-diene series can be determined from the value of J23. In all cases this value is small, about 2 Hz, suggesting that the proton at C-3 is quasi-axial and hence that the methoxyl group is equatorial. This assignment is supported by the observation of diaxial couplings (/3ax 4ax w 10 Hz) between protons at C-3 and C-4 (19-21, 55, 56). 

As in the Erythrina group, the stereochemistry at C-3 may be assigned from coupling constant data however, chemical shift data can also be used as an indicator of stereochemistry. For example, in the schelhammericine (81a) series (35-methoxyl), the methoxyl resonance occurs at <5 2.74 ppm... 

In this bicyclic case the palladium and methoxyl groups are trans to each other 1X>. A cis stereochemistry would have been expected on the basis of the ethylene oxidation mechanism. Trans-addition, however, is unusually favorable in the bicyclic examples. Although addition to the exo positions is generally strongly preferred, it cannot occur here if the favorable chelating effect of the second double bond is to be obtained. As a result, only the solvent methanol can attack from the exo side. The endo cis adduct has not been prepared and it conceivably could rearrange to the trans isomer even if it were formed initially. Clearly, more work needs to be done on the stereochemistry of the addition reactions. 

Methoxyvincamine (vincine, XXXV R = OMe), whose ring A methoxyl is so placed because of its UV-spectrum and a color reaction specific for that position, had properties (Chart III) that paralleled those of vincamine (21). This conclusion was reached independently on the basis of mass spectral comparisons (18). The stereochemistry of both alkaloids is regarded as being the same (21). Tetradehydro compounds (XXXVII) were formed by lead tetraacetate oxidation, and XXXVII... 

Reductive amination of methyl ketoreserpate was studied in detail. The use of re-propylamine in the presence of a palladium-charcoal catalyst led not only to the expected mixture of a- and /3-amino derivatives (X), but also to a methyl 17-demethoxy-18-deoxy-l 8-re-propyl -aminoreserpate (XII). In the last case, no attempt was made to define the stereochemistry at C-16 and C-18. Similar eliminations of the C-17 methoxyl under basic conditions were also encountered with other ketone derivative. Reductive aminations were also effected with secondary amines. Piperidine yielded as the sole insolable product the... 

Development of a carbocation center due to loss of chloride ion can account for the loss of stereochemistry at this carbon. It seems reasonable to write this step after removal of a proton to give the anion because, if chloride loss occurs before anion formation, the carbocation would be expected to react with solvent before the anion could be formed. In that case one might expect to isolate some of the compound in which chloride had been replaced by methoxyl. The effect of the solvent on the stereochemistry of the reaction is due to its ability to solvate the intermediate charged species involved in a stepwise mechanism. 

Regioselectivity and stereochemistry have been studied in the case of the anodic methoxylation of A-acylpiperidines and A-acylmorpholines [234]. Because of steric constraints imposed by the intermediate formation of the planar A-acyhminium ions, substitution is directed to the secondary carbon rather than to the tertiary position. The same reason accounts for the axial methoxylation in this reaction. 

Utley and Yates [276] reported an interesting stereochemistry and regiochemistry of methoxylated prdoucts derived from 4-phenylcyclohexene-2-carboxylic acid ... 

The anodic dimethoxylation of simple cyclic olefins, such as cyclohexenes, results in the predominant formation of ra/w-dimethoxycyclohexanes [303,305]. However, Barba and CO workers [306] reported that the stereochemistry of l,2-dimethoxy-l,2-dihydroace-naphthene derived from acenaphthene is drastically influenced by the anode material. Palasz and Utley [307] have reported that jV-acetylpiperidines are methoxylated via the enamide intermediate species formed by the oxidation. 1,3-Dienes are also 1,4-dimethoxylated in low stereoselectivity [293]. The anodic methoxylation of or-pinene proceeds similarly to the acetoxylation, resulting in the formation of two sets of stereoisomeric products [308]. 

The stereochemistry (cis and trans) of the methoxylated furans has been examined [309]. In most cases the rrawj -isomers are the major products. 

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