Intramolecular F-C alkylation

Scheme 35.25 Intramolecular F-C alkylation and creation of quaternary stereocenters.

It might be pointed out that, in 2007, the concept of SOMO catalysis was employed for F-C alkylation with simple aldehydes. The reaction of octanal with N-Boc-pyrrole afforded the formyl a-arylated product in 85% yield and 84% ee [49]. Following this preliminary encouraging report, intramolecular F-C type a-arylations of simple aldehydes incorporating electron-rich aromatic nuclei were reported in 2009 with proposed mechanisms based on MacMillan s SOMO activation [5, 50b] (see Section 35.4, Scheme 35.29 for detailed examples). 

Recently, the group of Hanessian reported an extension of MacMillan s organocatalytic aromatic alkylation to 3-aminocrotonaldehyde in the concise synthesis of an advanced precursor of a drug prototype for the treatment of migraine headaches [83]. An example that does not involve indoles as aromatic nucleophiles but pyrroles in the synthesis of natural products was reported in 2006 by Banwell and coworkers [84]. They accompHshed, via the common intermediate 94 obtained by means of an intramolecular F-C type alkylation, the syntheses of the alkaloids (—)-rhazinal, (—[-rhazinilam, (—[-leuconolam, and (-l-)-ept-leuconolam via the highly enantioselective creation of a quaternary stereocenter (Scheme 35.25). 

Regioselective F-C acylations of carboxylic anhydrides can be accompanied by other Lewis acid mediated reactions in tandem. Recently, a general method for the Lewis acid mediated intramolecular cyclization of keto ester alkyl substituted arenes to functionalized 1-indanones was reported by Pillion. Thus treatment of Meldrum s acid analogue 23 under a variety of... 

Comito, R. J., Finelli, F. G., MacMillan, D. W. C. (2013). Enantioselective intramolecular aldehyde a-alkylation with simple olefins direct access to homo-ene products. Journal of American Chemical Society, 135, 9538-9361. 

Another type of reaction leading to the incorporation of the Co-C alkyl chain inside the salen ligand set has been developed by Dreos et al. If the dimer 115 was left for a longer time in contact with the reaction mixture, an intramolecular reaction occurred between the chloromethyl group and the equatorial chelate. The unidentate ligands on cobalt can be replaced quantitatively by Af-Melm, leading to a complex 116 in which the / -f -geometry was maintained. If chiral amino acids were used, the diastereoisomers 117 could be separated (Scheme 14). ... 

An alternative approach to thienothienopyridines involves intramolecular electrophilic attack at C-3 of the thiophene ring. In this way, the thienothiophene 82 can be cyclized to the benzothieno[2,3-/]thieno[2,3-c]pyridine 83 upon treatment with polyphosphoric acid (PPA) at 150°C (Equation 3). Similarly, treatment of the amide 84 with POCI3 gives the corresponding 1-alkyl-3,4-dihydro-benzothieno[3,2-g]thieno[3,2-f]pyridine 85 <1999PS(153)401> (Equation 4). 

Recent results on the chemistry of persistent vinyl cations are summarized. / , / -Disilyl-substituted vinyl cations were synthesized by intramolecular addition of transient silylium ions to alkynes. The vinyl cations are stable at ambient temperature and were isolated in the form of their tetrakispentafluorophenylborate and hexabromocarboranate salts. The vinyl cations were characterized by IR and NMR spectroscopy and by X-ray crystallography. The experimental results for the a-alkyl- and a-aryl-substituted vinyl cations confirm their Y-shape structures, consisting of a linear dicoordinated, formally positively charged a-carbon atom and a trigonal planar coordinated /f-carbon atom. In addition, the spectroscopic data clearly indicate the consequences of, / -silyl hyperconjugation in these vinyl cations. Scope and limitations of the synthetic approach to vinyl cations via addition of silylium ions to C=C triple bonds are discussed. 

Type iii-c reaction leads to the formation of (68). In the case of 6-alkenoic acids an intramolecular addition takes place. The Kolbe electrolysis of f)- N-allylamino)alkanoate (83) in the presence of a co-acid (84) gave 3-alkyl-substituted pyrrolidine (85) through an intramolecular... 

Intramolecular ring formation is also found to occur by reaction of the C—H bond of an alkyl group attached directly to the phosphorus. For example, if /ran.s-PtCl2[P(f-Bu)2H-Pr]2 is heated in 2-methoxyethanol solution, the product is thought to be the complex with a five-membered chelate ring (XV) formed by reaction of the terminal methyl of the n-propyl group. 

The C(2)-C(3) olefin of a l,4-benzodiazepin-5-one regiospecifically captured an alkyl radical intramolecularly in a 5-f vo-/r/g-proccss that is the critical step in an approach to the constmction of the fused tricyclic system found in the pyrrolo[2,l-f][l,4]benzodiazepine class of antitumor antibiotic. Treatment of the alkyl bromide 46 with Bu3SnH afforded the tricyclic product 47 in 90% yield, a reaction that proceeded with equal efficiency with the alkoxy aryl ring substituents found in the naturally occurring ( )DC-81 (Scheme 18) <19990L1835>. 

Formation of small amounts of a by-product - F-methylcyclobutane 69 - (in reaction of HFP and TFE) catalyzed by ACF was rationalized as a result of similar intramolecular alkylation reaction of the C=C bond in intermediate carbo-cation 70, and it is probably the first example of electrophilic 2+2 cycloaddition reaction of fluoroolefin ... 

Erom a formal point of view the reaction of kinetically stabilized phosphaalkynes with 1,3-dienes should furnish 1-phosphacyclohexa-l,4-dienes. However, at 90°C with alkyl-substituted phosphaalkynes the primarly formed Diels-Alder adducts have not been detected, because the initial [4-f 2] cycloaddition was followed by an ene-reaction and a final intramolecular [4-1-2] cycloaddition to give diphosphatricyclooctenes. 

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