Aldehydes, conjugated from ketones

Double bonds in conjugation with the carbon-hetero multiple bond also lower addition rates, for similar reasons but, more important, may provide competition from 1,4 addition (p. 977). Steric factors are also quite important and contribute to the decreased reactivity of ketones compared with aldehydes. Highly hindered ketones like hexamethylacetone and dineopentyl ketone either do not undergo many of these reactions or require extreme conditions. 

The phenols need to be protected as their methyl ethers 67 and functionalisation by SeC>2, as described earlier in this chapter, gives the keto-aldehyde 68. To get 65 we should have to reduce the ketone in the presence of the aldehyde but the workers at Boehringer discovered a shortcut reductive amination using hydrogenation reduced both the imine (from i-PrNH2 and the aldehyde) and the ketone to give 69 and hence, by deprotection, metaproterenol 64. Notice that the aldehyde in 68 is more electrophilic than the conjugated ketone so it forms the imine needed for reductive amination. 

The overall result of a conjugate addition is the addition of a proton and a nucleophile to the CC double bond. However, this reaction differs greatly from the additions discussed in Chapter 11, in which the electrophile adds first. Here, the nucleophile adds in the first step. This reaction does not occur unless there is a group attached to the double bond that can help stabilize, by resonance, the carbanion intermediate. In many cases this is the carbonyl group of an aldehyde or a ketone. However, other groups, such as the carbonyl group of an ester or a cyano group, also enable this reaction to occur. 

In the presence of suitable catalysts, /3-lactones are formed by the action of ketene on aldehydes and ketones. Many catalysts have been used those preferred for aldehydes include boric acid, triacetyl borate, zinc thiocyanate, and zinc chloride. Ketones require stronger catalysts such as boron ttifluoride etherate. The reactions ate conducted at low temperatures (0-10°) to minimize polymerization of the product. Yields of /6-lactones from formaldehyde and acetaldehyde are 85%. The /3-lactones formed from conjugated olefinic ketones decompose to dienoic acids which isomerize to olefinic S-lactones. ... 

The addition of metalated sulfones to aldehydes or ketones is a reversible reaction and the principal cause of failure in the Julia alkenation results from an unfavorable equilibrium at this stage. The reverse reaction is favored when the P-alkoxy sulfone adduct is sterically encumbered. Adducts derived from ketones are more vulnerable than those derived from aldehydes. Stabilization of the sulfone anion by conjugation with an aromatic ring or chelation with a proximate heteroatom are also important contributors to favoring the reverse reaction. However, by varying the metal counterion, the position of equilibrium can be adjusted. For example, the lithio derivative of the sulfone (61 Scheme 24) failed to... 

Norrish Type I cleavage reactions dominate in the gas phase photochemistry of many acyclic aldehydes and ketones, whereas in the liquid phase this process is less common and alternative pathways (ii, iii, v) dominate. When no suitable C-H bonds are present to allow hydrogen abstraction reactions, however, this process will also constitute an important synthetic method for the cleavage of a-C-C bonds in solution. One important subsequent reaction of the resulting acyl and alkyl radicals is carbon monoxide formation and radical combination. Overall CO extrusion results which represents a versatile method for the formation of C-C single bonds from ketones. When cyclic substrates (cycloalkanones but not conjugated cycloalkenones which exhibit a different photochemistry) are used, ring... 

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