Alkylative cyclizations

N-benzylaniline with phosgene, and then with sodium azide to produce carbonyl azide 52. On heating, nitrogen is evolved and a separable mixture of nitrene insertion product 53 and the desired ketoindazole 54 results. The latter reaction appears to be a Curtius-type rearrangement to produce an N-isocyanate (54a), which then cyclizes. Alkylation of the enol of 54... 

Scheme 3.7. Samarium(ll)iodide-induced domino radical cyclization/alkylation procedure...

In another process, a dialkyl a-methyldiglycolate (formed from an alkyl lactate and an alkyl monochloroacetate) is reacted with dialkyl oxalate in the presence of a sodium alkoxide and dimethylformamide. The reaction product is cyclized, alkylated, hydrolyzed, and decarboxylated [187]. 

Fig. 17 Total synthesis of methyl curcurbate 76 and methyl epijasmonate 77 via a radical-polar 5-exo cyclization/alkylation sequence...

From these discoveries branched his work in hydrogenation (both organic and inorganic), isomerization, polymerization, condensation, cyclization, alkylation, and related reactions... 

The reagents used for the completion of the purine heterocycle are essentially the same as those used for the Traubc synthesis. The purine ring is formed by condensation with derivatives of formic acid or other carboxylic acids. Alternatively, formylation of the amino group is accomplished by a mixture of formic acid and acetic anhydride followed by cyclization. Alkyl esters or trialkyl ortho esters are also versatile synthons for ring closure. Moreover, heating in formamide or cyclization with urea or thiourea provides a satisfactory route. Condensations with isothiocyanates show unusual versatility leading to 2-sulfanylpurin-6-ols. From carbonic acid derivatives, cyclization is reported with chlorocarbonic esters, diethyl carbonate or carbon disulfide. 

In this single cyclization/alkylation cascade, two C - C bonds, one C - N bond, a carbonyl group, a tertiary and a quaternary stereocenter have been generated. 

Superacids such as HF-SbFs have been used to cyclize alkyl phenyl ketones to the corresponding tetralone derivatives in good yield, as shown by the example in equation (111), ... 

II,A,1, Scheme 2) by cyclization/alkylation in a one-pot reaction then the reaction is... 

Reaction of 1,3-diones with propargylic alcohols leads to 3-acylfurans. Using other Lewis acids such as FeCU the reaction stops short of cyclization. Alkylation by alkenes (styrene, norbornene, cyclopentadiene, dihydropyran,. ..) affords moderate yields of the adducts.Again, InCU appears to show a special catalytic activity, as AICI3, TiCU, MnCl2, Bids are ineffective. 

The rapid reaction of LiMe2Cu with trityl halides in ether produces trityl radicals, as shown by ESR. The reaction with a cyclizable alkyl halide, 6-iodo-l-heptene, produced the cyclic coupled product. Both results are strongly indicative of the intermediate radical formation by a singleelectron transfer pathway. 

In 2007 we developed a one-pot cyclization-alkylation reaction of a cyanoether to generate tetrahydropyrans (Scheme 37.22). The process involves the treatment of 90 with large excess of lithium 1,1,1,3,3,3-hexamethyldisila-zide (or lithium bis(trimethylsilyl)amide) (LiHMDS)... 

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