Overriding normal Friedel-Crafts regiochemistry in cycliacylation. Regiospecific carbodesilylation and Parham cyclization routes to 7-methoxy-1-indanols

Strategies Based on Aryllithium and N‐Acyliminium Ion Cyclizations for the Stereocontrolled Synthesis of Alkaloids and Related Systems

“…[27] In this context, bismuth(III) triflate has been found to promote the formation of cyclic acyliminium ions in remarkably low amounts (1 mol-%), suitable for both inter- and intramolecular reactions. [28] As depicted in Scheme 12, Bi(OTf) 3 -catalyzed intramolecular cyclizations of the acetoxylactams 39, obtained from the imides 38, took place in acetonitrile at room temperature, in an improvement on the results previously obtained for these substrates with TFA. [29] Although the Bi(OTf) 3 is tolerant towards the presence of an N,O-acetal functionality in 39 (X = O) and also of methoxy groups (R = OCH 3 ), substrates containing an S,N-acetal function (X = S) undergo cleavage of the S-C linkage under the reaction conditions.…”

“…[52] High diastereoselectivities were found in cyclizations of N-(1-alkoxyalkyl)-N-phenethyllactams to tetrahydroisoquinolines with substituents at the C-3 or C-4 positions. Reversal of diastereoselection was observed on changing from phenyl to cyclohexyl or tert-butyl substituents, which was attributed to a balance of syn-axial and A (1,3) interactions. In this context, additions of organolithium compounds to the chiral nonracemic l-DOPA-derived succinimide 97a (Scheme 30) yielded the oxo amides 98 and 99, which were cyclized diastereoselectively upon treatment with BF 3 ·OEt 2 , to afford the 5,10b-trans-pyrroloisoquinolones 100 and 101 with high ees (99 %) but in only moderate overall yields (34-36 %).…”

“…In most cases described in the literature, the most favored transition state would minimize A (1,3) strain, according to Hart's model. [57] Thus, for intramolecular cyclizations of π-nucleophiles on N-acyliminium ions with substituents adjacent to the nitrogen atom, an axial orientation is preferred in order to avoid A (1,3) strain between the substituent and the carbonyl function of the N-acyl group (conformation II). This results in the preferred formation of cis diastereomers when R 1 is hydrogen and a Lewis acid is used, as has been described in a number of examples.…”

“…The 6,11b relative stereochemistry obtained for these products can be explained in terms of the attack of the aromatic ring in a conformation such as A (Figure 2), which minimizes A (1,3) strain between the hydroxymethyl group, which would be complexed with the Lewis acid, and the lactam carbonyl group in the transition state. The hydroxymethyl substituent thus controls the relative stereochemistry of the C-11b stereogenic center.…”

“…When the internal electrophile is a carboxylate derivative, this anionic cyclization could be considered an anionic Friedel-Crafts equivalent, with the advantage that it lacks the electronic requirements of the classical reaction. Although it is possible to use carboxylic acids [3] or esters, [4] carbamates have proven to be much more effective internal electrophiles in Parham cycliacylations.[5] Amides are also useful electrophiles in Parham cyclizations, and it has been reported that in some cases there is an influence of the natures of the substituents at the nitrogen atom on the course of the cyclization reaction. [6,7] [a] Departamento In connection with our interest in aromatic lithiation, we have developed an anionic cyclization approach directed towards the construction of the pyrrolo[1,2-b]isoquinolone core based on N-(o-halobenzyl)pyrrole-2-carboxamides, showing that Weinreb amides and morpholine amides function as excellent internal electrophiles.…”