Subject intramolecular alkylation

Interest in the total synthesis of the Aspergillus terreus derived quadrone fi06), an antitumor agent has been very intense. Success was first realized in Danishefsky s laboratory Once 601 was reached, its sidechain was elaborated and ring closure effected (Scheme LII). Condensation of 602 with 1-tert-butoxy-l-tcrt-butyl-dimethylsiloxyethylene in the presence of titanium tetrachloride and subsequent desilylation resulted in introduction of an angular acetic acid moiety. The two sidechains were next connected by intramolecular alkylation and the resulting keto add was subjected to selenenylation in order to produce 603. The a, P-unsaturated double bond was used to force enolization to the a position. Indeed, 604 was... 

When the benzene-insoluble residue obtained at 200° C was subjected to nonreductive alkylation (33) the solubility was restored to 80%, and this strongly implies that the generation of new functional groups is responsible for the lower solubility at this temperature. However, in view of inter- or intramolecular alkylations that may accompany the cleavage reactions, it is not possible to correlate the extent of degradation with changes in the molecular weights. 

There are a few examples of intramolecular alkylation and related processes involving N-1. Base-catalyzed cyclization of the appropriate 2-substituted thioacid derivatives have given (62) and (63). In addition cyclization of a series of ketones (64) gives the tertiary alcohols (65) which are subject to dehydration (Scheme 21) (74CRV279). 

A slightly different approach to 850 takes advantage of an intermolecular carbenoid displacement and intramolecular alkylation to construct the pyrrolizidine ring (Scheme 128) [193,194]. The precursor is prepared from 875 (R==OH — OEt —> SPh) and, for convenience, the protecting acyl group is replaced with a MOM group, which gives 876 as an 8 1 mixture of trans and cis phenyl sulfides. The major ra 5-sulfide is subjected to a carbenoid dis-... 

The preparation of 620, a tricyclic intermediate suited for elaboration into quadrone, has been reported by Monti and Dean Following introduction of the proper C5, stereochemistry by alkylation of 618 under kinetically controlled conditions, diketone 619 was subjected to acid-catalyzed rearrangement. After functional group manipulation, a tandem intramolecular aldol-pinacol rearrangement gave 620. 

Theoretically, the regioselectivity observed in photochemical [2 + 2] cycloaddition of 56 with 1,1-dimethoxyethene is in good agreement with experimental results and has been explained on the basis of pertubational molecular orbital theory." Hartke and co-workers" described an interesting contrast in the reactivity of tropolones in an intramolecular Diels-Alder reaction (Scheme 6.18). Thus, alkylation of 64a and 64b with 65 gave 66a and 66b, respectively, that were subjected to cyclization in refluxing toluene. Whereas 66a decomposed under the reaction conditions, 66b afforded 67b in high yield. 

When the alkyl hydroperoxide has been fully formed, only one half of the oxidizing power of the oxygen has been utilized. Alkyl hydroperoxides are therefore unstable, the stability being dependent upon the structure. Tertiary hydroperoxides are the most, and primary hydroperoxides the least, stable. The degradation reaction, which is essentially a second stage in the oxidation, may be either inter- or intramolecular the degradation may be either bi- or monomolecular. The rate of degradation is a function of the temperature and is easily subject to catalysis. 

The intramolecular nitrogen-trapping protocol used by Banwell has also been successfully exploited in the assembly of spirocyclic frameworks relating to the aromatic erythrina alkaloids.24 However, when it was applied to the synthesis of nonaromatic spirocycles, as found in histrionicotoxin, the flexible alkyl tether proved to be problematic.25 In this study, gem-dichlorocyclopropane substrate 37 was initially subjected to silver(I) salts under a variety of conditions only to provide solvolysis and elimination products without any indication of trapping by the pendent... 

Gutman,50 in his process route, which did not report any yields, hydrogenated the pyridine ring first to access the piperidine moiety and constructed the indanone ring system via an intramolecular Friedel-Crafts acylation (Scheme 5). Hydrogenation of diester 31, obtained from condensation of 4-pyridine carboxaldehyde and dimethyl malonate, followed by benzylation of the piperidine intermediate afforded A-benzylated piperidine 32. Alkylation of 32 with 3,4-dimethoxybenzyl chloride (33) and subsequent hydrolysis gave dicarboxylic acid 34. Subjection of 34 to strong acid resulted in intramolecular Friedel-Crafts acylation and in situ decarboxylation to provide 3. 

In view of these many precedents it is surprising that the intramolecular displacement of the sulfur function of methionine derivatives has not been utilized for selective cleavage of methionine peptides. The method has only recently been applied to a number of methionine peptides which according to the following scheme (CXX-CXXIII) were first converted to sulfonium salts and then subjected to intramolecular (imino) lactonization and hydrolysis by short heating in water (Lawson et al., 1961). Table XV shows the strong influence of the nature of the added alkyl group on the yield in... 

SnCU-promoted intramolecular additions of allylsilanes to /3-lactones proceed smoothly to give differently substituted cyclopentanes (Eq. 61) [94], When the a-ben-zyloxy-/3-lactone is subjected to standard cyclization conditions, the expected cyclopentane product is only obtained as a minor product the major product, isochroman, is derived from a Friedel-Crafts alkylation (Eq. 62). 

Lewis acid catalyzed reactions of silyl enol derivatives of esters (ketene acetals) with 5n1-reactive alkylation agents are well known, but space limitations have prevented coverage of this subject here. The reaction shown in equation (11), which was employed by Pattenden and coworkers in their synthetic studies on forskolin, provides an example of an intramolecular Mukaiyama reaction of a silyl enol ester derivative. 

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