Dimethylallyl substituents

Streptocarpus (Gesneriaceae), e.g. catalponone (compare Figure 4.56), and this can be transformed to deoxylapachol and then menaquinone-1 (Figure 4.58). Lawsone is formed by an oxidative sequence in which hydroxyl replaces the carboxyl. A further interesting elaboration is the synthesis of an anthraquinone skeleton by effectively cycliz-ing a dimethylallyl substituent on to the naph-thaquinone system. Rather little is known about how this process is achieved but many examples are known from the results of labelling studies. 

This group contains carbazoles with a dimethylallyl substituent attached to C-l or C-4, as well as those derived as a result of cyclization of this dimethyallyl group with a phenolic group at the ortho position. Girinimbilol (66), C18H19NO, mp 106°C, an alkaloid isolated from the stem bark of... 

Only very few flavones of this type exist, in most cases showing various other types of substituents as well. (9-prenylation is known to occur at position 6, 7, or 4 -OH. Most of the substituents are 3,3-dimethylallyl structures. Whereas epoxyprenyl derivatives have been reported from the aerial parts of Achyrocline flaccida (Asteraceae), a new compound with 4 -0-dimethylallyl substitution was later reported from the leaves of Ficus maxima (compound 128, Table 12.3). There is no indication of external accumulation in any of the plants listed. Millettocalyxin B (compound 129, Table 12.3) from the stem bark of Millettia ery-throcalyx represents an example of a mixed structure (methylenedioxy- and (9-prenylsubstitu-tion). Similarly, ovalifolin (compound 131, Table 12.3) has a furano-substitutent in addition and is being reported for two new sources of Fabaceae. The name ovalifolin (published 1974) has priority for this furanoflavone its use for a structurally different compound from Ehretia ovalifolia is, therefore, obsolete. 

In allylic systems, favorable overlap of the p orbitals of the n system should require a coplanar arrangement of the three sp2 carbons and their five substituent atoms evidence that such a structure is indeed preferred comes, for example, from proton magnetic resonance observations that demonstrate barriers to bond rotation in the isomeric dimethylallyl ions 21, 22, and 23. These ions form stereo-specifically from the three dimethylcyclopropyl chlorides (Section 12.2), and barriers to rotation about the partial double bonds are sufficiently high to prevent interconversion at low temperature. At — 10°C, 21, the least stable isomer,... 

Despite the success in the 1,3-diphenylallyl system, use of many of these ligands in the alkylation of 1,3-dialkylallyl system as Equation 8E.4 has produced mixed results, as summarized in Table 8E.5. With the phosphinooxazoline-type ligands, good selectivities (>90% ee) are still obtained from the reactions of substrates possessing bulky allylic substituents such as isopropyl groups (entries 8-10), but smaller substrates such as 1,3-dimethylallyl derivatives give only a modest level of enantioselectivities (entries 1 -7). The disparity between these results appears to be sterically derived as the enhanced preference of syn versus anti orientation in the 7t-allyl structure by the bulky phenyl or isopropyl groups may not be present with the smaller substrates. 

D-ring modifications most often entail variation of the N- substituent. In this series the pattern of activity is much the same as that in other rigid opioids. Groups such as n-propyl, allyl, dimethylallyl, and CPM afforded antagonists... 

In all of the preceding series profound effects on pharmacological responses were exerted when the substituent on nitrogen varied (p. 29). Groups such as allyl, dimethylallyl, CPM, and CBM tend to endow the molecule with antagonist properties, whereas N-Me and IV-phenethyl afford agonist properties. 

A parallel trend is observed for MgBr2-promoted additions of cis- and trans-crotyl tributylstannanes to a-benzyloxy aldehydes but the effect is much smaller (Table 9) [18], In such reactions the orientation of the allylic stannane and the chelated aldehyde is governed by steric effects in which the vinylic y-hydrogen orients over the five-membered chelate (Fig. 4). Support for this picture is provided by competition experiments in which y3,)8-dimethylallyl tributyltin was found to be markedly slower than the crotyl or allyl derivatives in additions to a-benzyloxypropanal. The observed rate decrease was attributed to the disfavored relationship of a vinylic methyl substituent with the chelate ring resulting in unfavorable steric interactions. 

Because of the low reactivity of the tertiary alcohol, alkylation of the 014-hydroxyl with alkyl halides such as propyl or isoamyl halides was unsuccessful [Schmidhammer H, unpublished observations]. Therefore, allylic halides were employed to introduce 14-O-alkenyl substituents using similar conditions as described above [ 43—461. Catalytic hydrogenation afforded the corresponding 14-O-alkyl derivatives [43 -5]. Thus, 14-hydroxy-5-methylcodeinone (20) was treated with 3,3-dimethylallyl bromide in DMF in the presence of NaH to give compound 21, which underwent catalytic hydrogenation to yield 14-O-isoamyl-substituted morphinan 24 (Scheme 5) [43]. Similarly 14-phenylpropoxymorphinans 25 and 26 were prepared from 14-hydroxycodeinone (3) and 21, respectively, via intermediates 22 and 23, which were obtained by alkenylation using cinnamyl bromide (Scheme 5) [44, 45],... 

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