Ketones medium-sized

The chemical properties of cycHc ketones also vary with ring size. Lower members (addition reactions, than corresponding acycHc ketones. The Cg—C 2 ketones are unreactive, reflecting the strain and high enol content of medium-sized ring systems. Lactones are prepared from cycHc ketones by the Bayer-ViUiger oxidation reaction with peracids. S-Caprolactone is manufactured from cyclohexane by this process ... 

Cyclic enamines with an isomeric position of the double bond have been obtained by the addition of Grignard reagents to five- (78-81), six- (82-86), seven- (87-90), and thirteen- (89-91) membered lactams, whereas other medium-sized (92,93) lactams furnished amino ketones. The reaction has been extended to substituted lactams (94-98), and iminoethers (99,100). 

The direct comparison of 1 and 2 in a variety of RCM reactions also indicates a presumably close relationship between these catalysts (Table 1) [6]. Both of them give ready access to cycloalkenes of almost any ring size > 5, including medium sized and macrocyclic products. Only in the case of the 10-membered jasmine ketolactone 16 was the yield obtained with 2a lower than that with lc this result may be due to a somewhat shorter lifetime of the cationic species in solution. However, the examples summarized in Table 1 demonstrate that the allenylidene species 2 exhibit a remarkable compatibility with polar functional groups in the substrates, including ethers, esters, amides, sulfonamides, ketones, acetals, glycosides and even free hydroxyl groups. 

Three-cmbon ring expansionThe cyclic p-keto esters 1 with a 4-oxopentyl group at the a-position do not undergo the expected aldol condensation on treatment with KOC(CH3)3 in DMSO, but undergo ring expansion to medium-size ketones (2). The reaction may involve aldol and retro-aldol condensation. A similar... 

Azacyclanones,2 The usual syntheses of medium-sized azacyclanones involve Dicckmann or acyloin cyclization conducted under high dilution. An interesting new approach involves hydroboration-cyanidation (4, 446-447 5, 606-607) of a diunsaturated carbamate such as 1. llydroboration of I with thexylboranc followed by cyanidation under standard conditions gives the cyclic ketone 2 in moderate yield in one step. The product can be rcductivcly cyclizcd to the indoliz.idinc alkaloid 5-coniceine (3). 

Sometimes, aldehydes or ketones resulting from Dess-Martin oxidation are attacked intramolecularly by nitrogen atoms belonging to diverse functionalities, when such attack results in aminals inside stable medium-sized rings.82 Sometimes, these aminals suffer dehydration to enamines. 

An effect of the ring-size in addition to that observed in the elimination taking place in the reduction of vicinal dibromides, has been observed for medium-sized ring compounds which carry the electro-active group either in the side-chain or directly attached to the ring. The half-wave potentials of cycloalkyl bromides can be correlated with the half-wave potentials of cyclic ketones and their derivatives (Fig. 29). The observed relation indicates that the relative effect of ring-size on the reactivity is similar in all the reaction series compared. 

The partial steps of the conjugate addition in aminocatalytic reactions are in dynamic equilibrium, and thus products are formed under thermodynamic control. This fact is translated also in the geometry of the enamine intermediates, leading to the product, which can be either E or Z (Fig. 2.9). The geometry of the enamine depends on the catalyst structure and also on the substrate. Whilst proline-catalyzed reactions form preferentially, with a-alkyl substituted ketones, the. E-isomer, enamines derived from pipecolic acid afford an approximate 1 1 mixture of the E and Z isomers [6], In turn, small- and medium-sized cyclic ketones afford the E isomer. 

Scheme 10.3 Free radical retrosynthetic disassembly of bond d in 7. Advantages it does not necessitate the construction of a functionalised medium-sized ring. It forms the bicyclooctane ring system by a favourable 5-exo-trig pathway. Conformational and steric bias will allow the stereochemistry of the methyl a to the ketone to be controlled.

In this connection, transannular cyclization reactions between the ketonic carbonyl group and the amino nitrogen atom in medium-sized rings are of great interest. Cryptopine (10) is the most usual example, but not the best investigated case, of this kind. The appropriate inter-... 

The electrochemical reduction of y-oxoesters like 115, synthesized via the cyclopropane route, results in cyclization with participation of the olefinic unitn>. This reaction provides interesting cyclopentanol derivatives, which can be transformed to the corresponding cyclopentenes. Alternatively a fragmentation to medium sized ketones like 116 occurs after saponification and anodic oxidation 77>. 

The formation of no more than 20% of the conjugated ketone is due to a medium-sized ring effect. 3-Cyclohexenone contains a normal ring instead of a medium-sized ring, and it would be converted completely to 2-cyclohcxcnonc under equilibrium conditions.)... 

The formation of the twelve-membered lactone, IX/52, from the eight-mem-bered ketone, IX/51, prepared by alkylation of the aldehyde, IX/50, can be explained as an enlargement of a medium-sized ring. The driving force is probably the resonance stabilisation of the secondary nitro group in base (nitro-nate), compared to the tertiary nitro group in the starting material (Scheme IX/9) [29],... 

The carbonyl group is also normally ketonic when the nitrogen is no longer permanently held very close by being part of a medium-sized ring base CCV is an example of this (112). 

The two-carbon ring expansion which involves the [2 + 2] cycloaddition of enamines of cyclic ketones with electron-deficient acetylenes followed by thermal rearrangement of the resulting fused cyclobutenes (see Section II.E) has been successfully used in the synthesis of medium-size heterocycles. Examples include the preparation of compounds 407246, 408247 and 409248. 

Medium-sized cyclic ketones. A method for synthesis of 8-12 membered cyclic ketones is formulated in equation 1. ... 

Medium-sized cyclic ketones have been enantioselec-tively alkylated via their chiral lithioenamines to yield 2-alkylcycloalkanones in 80-100% ee. This procedure has also furnished a,a -dialkyl cyclohexanones in good enantiomeric excess (eq 2). Based on this protocol, regiospecific deutera-tion of 3-methylcyclohexanones has been achieved with good enantioselectivity. ... 

In contrast with medium-sized cyclic ketones, alkylation of macrocyclic ketones can afford either optical antipode depending on whether the lithioenamine is formed via kinetic ( -) or thermodynamic conditions (Z-enamine) (eq 3). Optically active a-alkyl macrocyclic ketones have been formed in 30-82% enantiomeric... 

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