Ring extension

The alkaloid rutaecarpine (111) was synthesized from l-oxo-1,2,3,4-tetrahydro-)3-carboline (183 R = H) by condensation with methyl anthranilate in the presence of phosphorous chloride or by heating 

The synthesis of the 1-methyl derivative of sempervirine was achieved by Woodward and McLamore who condensed 1-lithio-methyl-9-methyl-jS-carboline (386) with 2-isopropoxymethylenecyclo-hexanone (387) treatment of the reaction product with hydrochloric acid gave im -W-methylsempervirinium chloride (cf. 388). 

Compounds containing the yohimbine ring skeleton (390) have been synthesized by Hahn and his co-workers ma an intramolecular 

Mannich reaction, and this method has recently been extended and repeatedly applied (see Section IV, B, 2). It involves treating a 1-m-hydroxybenzyl-1,2,3,4-tetrahydro-jS-carboline derivative (389) with formaldehyde at pH 4.4. When the aqueous solution of the hydrochloride of the hydroxymethyl derivative so formed is made basic with sodium carbonate, the pentacyclic base (390) precipitates. 

A number of successful approaches to the indolo[2,3-a]quinolizinium ring system (252) (generally leading to reduced derivatives) have been reported by Swan and co-workers. By treating l-(4 -hydroxybutyl)-l,2,3,4-tetrahydro-j8-carboline (391) with hydrobromic acid followed by base, l,2,3,4-tetrahydro-12jEf-indolo[2,3- ]quinolizinium bromide 

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Ring-erweiterung, /. ring extension, -faser, /. annular fiber. 

Ring extension, to dihydro-1,4-thiazine. 35 to djhydro-1,4-thiazine, 36 Ring fusion, of some 2-methylthiazolium,... 

Table 13. Ring Extension of alicyclic P-hydroxycarboxylic acids by non-Kolbe electrolysis...

Non-Kolbe electrolysis of alicyclic p-hydroxy carboxylic acids offers interesting applications for the one-carbon ring extension of cyclic ketones (Eq. 35) [242c]. The starting compounds are easily available by Reformatsky reaction with cyclic ketones. Some examples are summarized in Table 13. Dimethylformamide as solvent and graphite as anode material appear to be optimal for this reaction. 

Non-Kolbe electrolysis of carboxylic acids can be directed towards a selective fragmentation, when the initially formed carbocation is better stabilized in the y-position by a hydroxy or trimethylsilyl group. In this way the reaction can be used for a three-carbon (Eq. 36) [335] (Table 14, No. 1) or four-carbon ring extension (Eq. 37) [27] (Table 14, Nos. 2-4). Furthermore it can be employed for the stereo-... 

The cationic pathway allows the conversion of carboxylic acids into ethers, acetals or amides. From a-aminoacids versatile chiral building blocks are accessible. The eliminative decarboxylation of vicinal diacids or P-silyl carboxylic acids, combined with cycloaddition reactions, allows the efficient construction of cyclobutenes or cyclohexadienes. The induction of cationic rearrangements or fragmentations is a potent way to specifically substituted cyclopentanoids and ring extensions by one-or four carbons. In view of these favorable qualities of Kolbe electrolysis, numerous useful applications of this old reaction can be expected in the future. 

Consequences of unsaturation. Unsaturation in the macrocyclic ring may have major steric and electronic consequences for the nature of the ring. Extensive unsaturation will result in loss of flexibility with a corresponding restriction of the number of possible modes of coordination. Further, loss of flexibility tends to be reflected in an enhanced macrocyclic effect . For example, if the metal ion is contained in the macrocyclic cavity, the loss of flexibility reduces the possible pathways for ligand dissociation and this tends to increase the kinetic stability of the system. As explained in later chapters, enhanced thermodynamic stabilities will usually also result. 

An application of this reaction to aromatic ring extension is noteworthy. As shown in Eq. 2.43, zirconacydopentadienes couple with diiodobenzene (63) to afford naphthalenes 64. When tetraiodobenzene (65) is used, octasubstituted anthracene derivatives 66 are obtained [7c],... 

The ring rearrangement of 8a-(l-hydroxy-alkyl)-hexahydro-oxazolo[3,4- ]pyridin-3-ones 163 upon treatment with sulfuryl chloride was reported in 2004 activation of the alcohol and ring extension produces 5,6-dihydro-l//-oxazolo[3,4-tf]azepin-3-ones 164 in excellent yields (Scheme 48) <2004H(63)17>. 

However, by considering models of the anti configured ylide (Fig. 3.18), it was concluded that the inclusion of a three-carbon tether forces the reactive centers to be too sterically constrained to suffer intramolecular cycloaddition with an alkyne dipolarophile. Conversely, the syn ylide is able to achieve the correct approach for such a process, despite the steric interaction with the phenyl ring. Extension of the interim chain by one methylene unit using 6-heptynal, introduced a greater degree of flexibility into the system, allowing for the formation of the expected diaster-eoisomers (Scheme 3.101). 

The ring extension Ap — R is faithfully flat (since R is the completion of the strict henselization of, 4p) and we know by Proposition 1.7.2 and the result of Crick mentioned above that the map... 

It is easily seen that R C R is finite flat and that R has only one maximal ideal. The field extension k C k is such that k = (k )p. Thus k k and k has a finite p-basis also. The ring R is Noetherian and complete because the ring extension R C R is finite flat. 

In the course of a total synthesis of resiniferatoxin, an unexpected ring extension occurred, when 1,3-dioxane 236a was treated with an acid in chloroform. The ring extension was confirmed by acid-catalyzed rearrangement of diol 236b into dioxepane 237 (Scheme 70) <20040L4371>. 

Since the rearrangement of silicon azides is known, we looked for some synthetic applications in organometallic chemistry. For example, ring extension reactions involving sila.imines intermediates can be described ... 

The radical cation of [ 1.1.1.1 Jisopagodane could be generated by y-UTadiation in a freon matrix. The corresponding EPR spectrum indicated two H hfc values, one of 0.95 (4 equivalent H) and one of 0.11 mT (4 equivalent H) showing that the D2d symmetry of the parent molecule was reduced to C2v This mirrors a slight ring extension but still a cyclobutanoid conhguration as confirmed by quantum mechanical calculations. 

The radical ring extension of a-alkyl-p-tin substituted cyclohexanones in the presence of azobis(isobutyronitril) (AIBN) and tributyltin hydride in diluted solution results in good to excellent yields of the ring-extended products [83] (Fig. 5). 

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