Syntheses Starting with Ketones or Aldehydes

By three reaction types (5), 4 and (5) in Thble 2-1 of Sect. 2.2, ketones or aldehydes are used as starting materials. Therefore, it is reasonable to treat them together in this section. At the end (Subsection 2.5.4) a related diazomethane synthesis (depicted many decades ago by Staudinger) will be added, although it is not strictly related to this section. From the synthetic point of view, it is not particularly interesting, but mechanistically it is worthy of discussion because nitrilimine, an isomer of diazomethane, is probably formed as a steady-state intermediate in this reaction. 

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Three different routes to the key compounds for the sila-Peterson elimination, the a-alkoxydisilanes 157, are described in the literature, namely A, reaction of silyllithium reagents with ketones or aldehydes B, addition of carbon nucleophiles to acylsilanes C, deprotonation of the polysilylcarbinols. In addition, method D, which already starts with the reaction of 2-siloxysilenes with organometallic reagents, leads to the same products. The silenes of the Apeloig-Ishikawa-Oehme type synthesized so far are summarized in Table 4. 

Show how Wittig reactions might be used to synthesize the following compounds. In each case, start with an alkyl halide and a ketone or an aldehyde. 

Cyclic hemiacetals and acetals are readily formed from y-hydroxyaldchydes," ketones, or acetals.Either the carbonyl compound or the alcohol is deblocked before spontaneous cyclization occurs. Aldehydes are regularly synthesized from alkeiies via ozonolysis or periodate cleavage. Acetal 7. a starting material for nucleoside analogs, is prepared directly by transacctalization of alcohol 6 with 1 % ethanol/hydrogen chloride. 

The ease with which alcohols are oxidized to aldehydes, ketones, or carboxylic acids (depending on the alcohol that you start with and the conditions that you employ), coupled with the ready availability of alcohols, provides the pathway necessary to many successful s)mthetic transformations. For example, let s develop a method for synthesizing ethyl propanoate, using any inorganic reagent you wish but limiting yourself to organic alcohols that contain three or fewer carbon atoms ... 

Starting with alkyl halides, we can prepare the appropriate Grignard reagents and in combination with different aldehydes or ketones, synthesize a series of compounds with branched hydrocarbon chains. 

The 1,3-dithiane anion can be prepared in two steps from the corresponding aldehyde (formation of thioacetal, followed by deprotonation). Another option is to start with formaldehyde. Alkylation of its 1,3-dithiane anion will introduce the required ethyl group. This method can be used to prepare a variety of 13-dithiane compounds, and can even be used to synthesize aldehydes and ketones (one or two alkylation steps, followed by hydrolysis). 

A recent and important example for a N-containing linker system is the hydrazone linker developed by the group of Lazny [253]. This system is useful for the immobilization of aldehydes and ketones via hydrazone bonding. The linker was synthesized starting from commercially available 2-(AT-methylamino)ethanol (or corresponding aminoalcohols) which is nitrosated with t-butylnitrite and subsequently reduced with lithium aluminum hydride... 

Aminopropanols, when reacted with cyanogen bromide, also afford 2-amino-(or imino)-dihydro-1,3-oxazines (Scheme 90) (64ZOB3427), and related thiazines are formed when allylic isothiouronium salts (207) are cyclized with trifluoroacetic acid and stannic chloride. The necessary starting materials are synthesized from aldehydes or ketones by the action of vinylmagnesium chloride and subsequent treatment of the product allyl alcohols (206) first with hydrogen chloride and then with a thiourea (Scheme 91) (77JHC717). 

Since the report by Carboni and Lindsey in 1959 on the cycloaddition reaction of tetrazines to multiple bonded molecules as a route to pyridazines, such reactions have been extensively studied. In addition to acetylenes and ethylenes, enol ethers, ketene acetals, enol esters and enamines, and even aldehydes and ketones have been used as starting materials for pyridazines. A detailed investigation of various 1,2,4, 5-tetrazines in these syntheses revealed the following facts. In [4 + 2] cycloaddition reactions of 3,6-bis(methylthio)-l,2,4,5-tetrazine with dienophiles, which lead to pyridazines, the following order of reactivity was observed (in parenthesis the reaction temperature is given) ynamines (25°C) > enamines (25-60°C) > ketene acetals (45-100°C) > enamides (80-100°C) > trimethylsilyl or alkyl enol ethers (100-140°C) > enol... 

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