Alkyl appendages

Tricyclic molecules having 10 carbon atoms are converted to adamantane with Lewis acids. Additional carbon atoms become alkyl appendages ... 

Corey has reported a novel method for the introduction of two alkyl appendages at the carbonyl carbon of ketones. Ketones react with the anion of diethyl allylthiomethylphosphonate (155) to give vinyl allyl sulphides such as (156) heating in the presence of mercury(ii) oxide induces a thio-Claisen rearrangement to yield the aldehyde (157), which can be further elaborated by various oxidation-reduction sequences to give, for example, the spiro-enone (158). 

The metal-based preparations of conjugated dienes represent the majority of the strategies employed to attain stereoselectively 1,3-dienes connected to aryl and/or alkyl appendages. The starting material can be stereodefined when double bonds or enynes are engaged. When alkynes or allenols are employed, two double bonds are generated in a stereoselective manner. 

The Y appendage of 2-cyclohexenone 191 cannot be directly disconnected by an alkylation transform. (y-Extended enolates derived from 2-cyclohexenones undergo alkylation a- rather than y- to the carbonyl group). However, 191 can be converted to 192 by application of the retro-Michael transform. The synthesis of 192 from methoxybenzene by way of the Birch reduction product 193 is straightforward. Another synthesis of 191 (free acid) is outlined in... 

Removal of the unsaturated side-chain appendage from C-8 in 22 provides diol lactone 23 and allylic bromide 24 as potential precursors. In the synthetic direction, a diastereoselective alkylation of a hydroxyl-protected lactone enolate derived from 23 with allylic bromide 24 could accomplish the assembly of 22, an intermediate that possesses all of the carbon atoms of PGF2o- It was anticipated that preexisting asymmetry in the lactone enolate would induce the... 

Chloromethylphosphonamide 104 has been alkylated with diastereoselectivities up to >95%. The corresponding azido compounds 106 were obtained by nucleophilic displacement, with partial to full stereospecificity <2000HA528>. This two-step process can lead to aminophosphonic acids after reduction of the azido group and hydrolysis of the chiral appendage (Scheme 7). 

One facile entry to intermediates possessing the y-lycorane skeleton involved the alkoxide-catalyzed cyclization of the isocarbostyril 34b, which was readily accessible by the N-alkylation of 34a, to provide the y-lycorane derivative 35 (104). The amino derivative 36 was available in three steps from the isocarbostyril 37 by a similar sequence of reactions, but several attempts to prepare the p-unsubstituted enone lactam 38 by this approach resulted in the loss of the N-(4-oxobutyl) appendage by a retro-Michael reaction and were unsuccessful. 

Alkylation of the corresponding dianion of acid 32 was very convenient and led to numerous 9-alkyl products. For example, analogue 58 was prepared via the LDA-generated dianion of 32, which was alkylated with f-butyl bromoacetate to provide acid-ester 64. Crude vinylsilane 64 was submitted to successive ozone addition and acidification. The resultant tetracyclic peroxide 65 was subsequently treated with trifluoroacetic acid to cleave the f-butyl ester to the free the acetic acid appendage of target 58 in 20% overall yield from 64 (Eq. 15). 

Access to analogues with higher substitution was easily achieved. From either the propionate ester 193 or acetic acid 188, we previously made the propionic acid appendaged 189, which was in turn alkylated to the gem-dimethyl acid 194 in 76% yield (93% based on recycled starting material). The vinylsilane of 194 underwent addition of ozone to eventually afford hydroperoxide 195, and final ring closure was accomplished with trifluoroacetic acid and acetone to afford gem-dimethyl analogue 169 in 19% overall yield from 194 (Eq. 20). 

It is now widely accepted that alkyl groups attached to heterocycles are not mere nonfunctional appendages but do undergo many reactions and do have important steric and electronic effects on the reactivity of the molecule as a whole. In the pyrazine series, alkyl groups have an additional interest because even quite simple... 

A milder alternative to the classical Gabriel synthesis, which allows the appendage of a protected primary amine to a secondary alkyl group, exploits the Mit-sunobu inversion2 as illustrated in Scheme 8.15.27 The method can also be adapted to the synthesis of -protected hydroxylamines [Scheme 8,16)22... 

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