Reactions with Keto-Compounds

Hydroxy(tosyloxy)iodo]benzene and Its Analogues Reactionswith Alkenes and Allenes. Reactions with Alkynes and Alcohols. Reactions with Keto Compounds. Reactions with Nitrogen, Sulfur, and Other compounds. 

Reaction of a-phenylsulfinyl acetate or ethyl a-(t-butylsulfmyl)acetate with one equivalent of ethylmagnesium bromide or iodide was shown to give the corresponding Grignard reagent 129 or 132, which upon reaction with carbonyl compounds afforded the corresponding adducts. Thus Nokami and coworkers prepared ethyl / -hydroxycarboxylates 130167, jS-keto esters 131168, a,/J-unsaturated esters 133169 and other derivatives by this method. 

The following types of compounds undergo coupling reactions with diazo compounds (a) Phenols, (b) Enolizable keto compounds of an aliphatic character, having a reactive methylene group which may be part of an open chain or a ring system, either homocyclic or heterocyclic. This group of compounds may be represented by the formula ... 

Oxazolones undergo Friedel-Crafts reactions with aromatic compounds to give keto intermediates which, under the reaction conditions, cyclodehydrate to give 5-aryl-oxazoles (Equation 7) <2005JOC4211>. 

Mixed coupling reactions, using two different carbonyl compounds, can be effected, but they generally lead to mixtures of products and are of limited use in synthesis. Intramolecular reactions with dicarbonyl compounds, on the other hand, provide a good route to cyclic alkenes. The keto-aldehyde 80, for example, gave the cyclic diterpene kempene-2, despite the presence of a saturated ketone... 

Figure 15. The reaction of p-nitrobenzylhydroxylamine with keto compounds.

The introduction of functionalized two-carbon side-chains, as found in (1) and (4) has received some attention. The usual way is by reaction of a suitable keto-derivative with a vinyl Grignard reagent, followed by functionalization of the vinyl group by way of epoxidation. In this way Fraser-Reid and Walker achieved a synthesis of pillarose (2,3,6-trideoxy-4-C-hydroxyacetyl-D- /zreo-hexose) (5) from the 4-uloside (6). As an alternative method, Brimacombe s group have published details of the use of 1-methoxyvinyl lithium, which reacts with keto-compounds to give a 1-methoxy vinyl side-chain capable of functionalization in various ways. For example, Scheme 2 shows its application to 1,2 5,6-di-0-isopropylidene-a-D-n6o-hex-3-ulose. Reaction of this reagent with methyl... 

These reversible reactions are cataly2ed by bases or acids, such as 2iac chloride and aluminum isopropoxide, or by anion-exchange resias. Ultrasonic vibrations improve the reaction rate and yield. Reaction of aromatic aldehydes or ketones with nitroparaffins yields either the nitro alcohol or the nitro olefin, depending on the catalyst. Conjugated unsaturated aldehydes or ketones and nitroparaffins (Michael addition) yield nitro-substituted carbonyl compounds rather than nitro alcohols. Condensation with keto esters gives the substituted nitro alcohols (37) keto aldehydes react preferentially at the aldehyde function. 

Reaction of the 17-keto compound (54) with potassium acetylide in liquid ammonia gives the 17a-ethynylandrost-5-ene-3) ,I7)5-dioI (55). ° Similar results have been obtained with A-ring aromatic 17-ketones. ... 

The reaction of 17-keto steroids with hydrogen cyanide (or acetone cyanohydrin) to form a mixture of the 17-cyano-17-hydroxy compounds, followed by dehydration and reaction with methyl Grignard reagent, is one of the earliest methods for the conversion of androstanes to pregnanes. 

Similar sulfenylation reactions of the 2-subsdtuted cyclic enamines of -keto carboxylic acid anilides are also possible, The trifluoromethanesulfenyl substitution takes place according to ring size Sulfenylation occurs at positions 2 and 5 with five-membered rings, at posibon 6 with six-membered tings, and at position 7 with seven-membered rings [5J (equation 4) (Table 1). Acid hydrolysis of the enamines proceeds readily to form the corresponding keto compounds. 

In a modified approach, the carbolinyl acetate 393 underwent a Mannich reaction with formaldehyde and acetone to give the keto ester 396 which, with base, cyclized to the diketone 397. This diketone (397) has recently been used to prepare a number of interesting pentacyclic compounds. 

---