Carbonyl compounds transformations

The usual base or acid catalyzed aldol addition or ester condensation reactions can only be applied as a useful synthetic reaction, if both carbonyl components are identical. Otherwise complicated mixtures of products are formed. If two different aldehydes or esters are to be combined, it is essential that one of the components is transformed quantitatively into an enol whereas the other component remains as a carbonyl compound in the reaction mixture. 

Diene carboxylates can be prepared by the reaction of alkenyl halides with acrylates[34]. For example, pellitorine (30) is prepared by the reaction of I-heptenyl iodide (29) with an acrylate[35]. Enol triflates are reactive pseudo-halides derived from carbonyl compounds, and are utilized extensively for novel transformations. The 3,5-dien-3-ol triflate 31 derived from a 4,5-unsaturated 3-keto steroid is converted into the triene 32 by the reaction of methyl acrylate[36]. 

There has been recent interest in naphtho-fused dithiepines as chiral acyl anion equivalents, particularly since the starting dithiol 128 can be obtained in enan-tiomerically pure form (89TL2575). This is transformed using standard methods into the dithiepine 129, but showed only moderate diastereoselectivity in its addition to carbonyl compounds. On the other hand, as we have seen previously for other systems, formation of the 2-acyl compound 130 and reduction or addition of a Grignard reagent gave the products 131 with much better stereoselectivity (91JOC4467). 

Novel aerobic oxidation method using A-hydroxyphthalimide as a catalyst (transformations of hydrocarbons to alcohols and/or carbonyl compounds) 99YGK24. 

The required nitrite esters 1 can easily be obtained by reaction of an appropriate alcohol with nitrosyl chloride (NOCl). The 3-nitroso alcohols 2 formed by the Barton reaction are useful intermediates for further synthetic transformations, and might for example be converted into carbonyl compounds or amines. The most important application for the Barton reaction is its use for the transformation of a non-activated C-H group into a functional group. This has for example been applied for the functionalisation of the non-activated methyl groups C-18 and C-19 in the synthesis of certain steroids. ... 

In order to allow further transformation to an indole, the carbonyl compound 8 must contain an a-methylene group. The hydrazone 1 needs not to be isolated. An equimolar mixture of arylhydrazine 7 and aldehyde or ketone 8 may be treated directly under the reaction conditions for the Fischer indole synthesis. ... 

The most generally useful method for preparing alkyl halides is to make them from alcohols, which themselves can be obtained from carbonyl compounds, as we ll see in Sections 17.4 and 17.5. Because of the importance of the process, many different methods have been developed to transform alcohols into alkyl halides. The simplest method is to treat the alcohol with HC1, HBr, or HI. For rea-... 

Since double bonds may be considered as masked carbonyl, carboxyl or hydroxymethylene groups, depending on whether oxidative or reductive methods are applied after cleavage of the double bond, the addition products from (E)-2 and carbonyl compounds can be further transformed into a variety of chiral compounds. Thus, performing a second bromine/lithium exchange on compound 4, and subsequent protonation, afforded the olefin 5. Ozonolysis followed by reduction with lithium aluminum hydride gave (S)-l-phenyl-l,2-ethanediol in >98% ee. 

In contrast to other terminal alkynes, the lithiated dimethylaminoethyne 40 does not give the corresponding alkynylcarbene but the cyclopropenylidene complex 41 (Scheme 7) [51]. Further addition of dimethylamine to 41 affords the substitution product 42 in excellent yield. This 2,3-bis(dimethylamino-cyclopropenylidene)pentacarbonylchromium (42) is extremely stable, and it cannot be transformed to the corresponding carbonyl compound, 2,3-bis... 

The oxidation of alcohols to the corresponding carbonyl compounds is one of the key reactions in organic synthesis and nnmerous methods have been developed over the years to accomplish this transformation [16], A general mechanism for Pd-catalysed aerobic oxidation is shown below (Scheme 10.5). 

Reaction of the carbanion of chloromethyl phenyl sulphoxide 409 with carbonyl compounds yields the corresponding 0-hydroxy adducts 410 in 68-79% yield. Each of these compounds appears to be a single isomer (equation 242). Treatment of adducts 410 with dilute potassium hydroxide in methanol at room temperature gives the epoxy sulphoxides 411 (equation 243). The ease of this intramolecular displacement of chloride ion contrasts with a great difficulty in displacing chloride ion from chloromethyl phenyl sulphoxide by external nucleophiles . When chloromethyl methyl sulphoxide 412 is reacted with unsymmetrical ketones in the presence of potassium tcrt-butoxide in tert-butanol oxiranes are directly formed as a mixture of diastereoisomers (equation 244). a-Sulphinyl epoxides 413 rearrange to a-sulphinyl aldehydes 414 or ketones, which can be transformed by elimination of sulphenic acid into a, 8-unsaturated aldehydes or ketones (equation 245). The lithium salts (410a) of a-chloro-/ -hydroxyalkyl... 

Reaction of optically active a-sulphinyl acetate 298a with prochiral carbonyl compounds proceeds with a high asymmetric induction - , the degree of which depends on the nature of substituents at the carbonyl group (equation 252 Table 22) . The jS-hydroxy sulphoxides 422 formed may be transformed to optically active p-hydroxycarboxylic esters 423 (equation 253) and optically active long-chain lactones 424 99 (equation 254). Corey and coworkers have used this method to introduce a chiral centre at C-3 in their synthesis of maytansin °°, and Papageorgiou and Benezra for the synthesis of chiral a-hydroxyalkyl acrylates 425 ° (equation 255). 

Silyl enol ethers and silyl ketene acetals also offer both enhanced reactivity and a favorable termination step. Electrophilic attack is followed by desilylation to give an a-substituted carbonyl compound. The carbocations can be generated from tertiary chlorides and a Lewis acid, such as TiCl4. This reaction provides a method for introducing tertiary alkyl groups a to a carbonyl, a transformation that cannot be achieved by base-catalyzed alkylation because of the strong tendency for tertiary halides to undergo elimination. 

For internal olefins, the Wacker oxidation is sometimes surprisingly regioselective. By using aqueous dioxane or THF, oxidation of P,y-unsaturated esters can be achieved selectively to generate y-keto-esters (Eq. 3.18).86 Under appropriate conditions, Wacker oxidation can be used very efficiently in transforming an olefin to a carbonyl compound. Thus, olefins become masked ketones. An example is its application in the synthesis of (+)-19-nortestosterone (3.11) carried out by Tsuji (Scheme 3.5).87... 

A mixture of 1,4-dioxane and water is often used as the solvent for the conversion of aldehydes and ketones by H2Se03 to a-dicarbonyl compounds in one step (Eq. 8.117).331 Dehydrogenation of carbonyl compounds with selenium dioxide generates the a, (i-unsaturated carbonyl compounds in aqueous acetic acid.332 Using water as the reaction medium, ketones can be transformed into a-iodo ketones upon treatment with sodium iodide, hydrogen peroxide, and an acid.333 Interestingly, a-iodo ketones can be also obtained from secondary alcohol through a metal-free tandem oxidation-iodination approach. 

Copper hydride species, notably Stryker s reagent [Ph3PCuH]6, are capable of promoting the conjugate reduction of a,( >-unsalurated carbonyl compounds [42], Taking advantage of this trustworthy method, Chiu et al. demonstrated in 1998 an intramolecular reductive aldol reaction in the synthesis of novel terpenoid pseudolaric acids isolated from Chinese folk medicine (Scheme 28) [43]. Two equivalents of [Ph3PCuH]6 enabled cycli-zation of keto-enone 104 to provide the bicyclic diastereomers 105 (66%) and 106 (16%). The reaction also was applied to the transformation of 107... 

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