Aldehydes Organic Syntheses procedures

The conversion of primary or secondary nitro compounds into aldehydes or ketones is normally accomplished by use of the Nef reaction, which is one of the most important transformations of nitro compounds. Various methods have been introduced forthis transformation (1) treatment of nitronates with acid, (2) oxidation of nitronates, and (3) reduction of nitroalkenes. Although a comprehensive review is available,3 important procedures and improved methods published after this review are presented in this chapter. The Nef reaction after the nitro-aldol (Henry reaction), Michael addition, or Diels-Alder reaction using nitroalkanes or nitroalkenes has been used extensively in organic synthesis of various substrates, including complicated natural products. Some of them are presented in this chapter other examples are presented in the chapters discussing the Henry reaction (Chapter 3), Michael addition (Chapter 4), and Diels-Alder reaction (Chapter 8). 

Sml2, which can be prepared conveniently from samarium powder and 1,2-diiodoethane in THF, finds application as a versatile one-electron reducing agent in organic synthesis. Two typical synthetic procedures mediated by Sml2 are the pinacol coupling of aldehydes and the Barbier reaction, as shown in the following schemes ... 

The corresponding silyl ethers are stable under the usual conditions employed in organic synthesis for the deprotection of silyl groups and were deprotected using photolysis at 254 nm in yields ranging from 62-95%. Therefore, the hydrosilylation of ketones and aldehydes followed by this deprotection procedure is formally equivalent to the reduction of carbonyl moieties to the corresponding alcohols. 

This new style of synthetic catalysis will of course not replace all normal synthetic methods. For many purposes, the standard methods and rules - e.g. aldehydes are more easily reduced than are ketones - will continue to dominate organic synthesis. However, when we require a synthetic transformation that is not accessible to normal procedures, as in the functionalization of unactivated carbons remote from functional groups, artificial enzymes can play a role. They must compete with natural enzymes, and with designed enzyme mutants, but for practical large-scale industrial synthesis there can be advantages with catalysts that are more rugged than proteins. 

The addition of an organomagnesium compound to an aldehyde is an excellent general method for preparing secondary alcohols, and the side-reactions referred to above are a problem only in particularly unfavourable cases. Large numbers of examples have been tabulated [A] and examples from Organic Synthesis are listed in Table 6.1. a,[3-Unsaturated aldehydes normally undergo mainly or exclusively 1,2-addition, as in the examples in Table 6.1. The following experimental procedure is typical. 

There has been considerable research into the electrolytic reduction of aromatic carboxylic acids to the corresponding aldehydes. A general procedure has been described in which key elements are the use of the ammonium salt of the acid, careful control of the pH and the presence of an organic phase (benzene) to extract the aldehyde and thus minimize overreduction. The method appears to work best for relatively acidic substrates for example, salicylaldehyde was obtained in 80% yield. Danish workers have shown that, under acidic conditions, controlled electrolytic reductions are possible for certain pyridine-, imidazole- and thiazole-carboxylic acids. In these cases, it is thought that the product aldehydes are protected by geminal diol formation. A chemical method which is closely related to electrolysis is the use of sodium amalgam as reductant. Although not widely used, it was successfully employed in the synthesis of a fluorinated salicylaldehyde. ... 

Since the discovery of thermally promoted allylation of aldehydes [9], allylstannanes have been widely used in organic synthesis as stable and stereodefined reagents for C-C bond formation. Although it had been reported that activated aldehydes [10] or allylstannanes with chloride on the tin [11] could be used for allylation, remarkably innovative technology for allylation was advanced by Naruta and by Sakurai and Hosomi [12]. They disclosed that allylation was promoted by addition of a Lewis acid this substantially expanded the versatihty of the aUylstaimane procedure. Because many allylation reactions have already been documented [1], the most recent progress in this field will be described after brief description of fundamental aspects. 

Abstract The possible utilization of room temperature ionic liquids (RTILs), instead of volatile organic compounds (VOCs), in the electrochemical procedures of organic synthesis has been discussed. The synthesis of p-lactams, the activation of carbon dioxide and its utilization as renewable carbon source and the carbon-carbon bond formation reactions via umpolung of aldehydes (benzoin condensation and Stetter reaction) and via Henry reaction have been selected as typical electrochani-cal methodologies. The results, related to procedures performed in RTILs, have been compared with those performed in VOCs. The double role of RTILs, as green solvents and parents of electrogenerated reactive intermediates or catalysts, has been emphasized. 

This procedure (Scheme 3.52) exhibits a very high degree of selectivity for the oxidation of primary alcohols to aldehydes, without any noticeable overoxidation to carboxyl compounds and a high chemoselectivity in the presence of either secondary alcohols or of other oxidizable moieties. An optimized protocol, published in Organic Synthesis for the oxidation of nerol (125) to nepal (126) (Scheme 3.53), is based on the treatment of the alcohol 125 solution in buffered (pH 7) aqueous acetonitrile with PhI(OAc)2 and TEMPO (0.1 equiv) atO°Cfor 20 min [145]. 

A recent review on the uses of bromodimethylsulfonium bromide ([Mc2S Br]Br, BDMS) in organic synthesis opened a subject of BDMS application for the one-pot synthesis of a-haloacrylates from stabilized phosphorus ylides and aldehydes in high Z/E ratios, together with other reactions.The procedure is suggested to involve a rapid in situ formation of mixed phosphonium-sulfonium ylides followed by conversion into a-halo-phosphonium yUde, e.g. Ph3P=C(Br)COOR, and subsequent Wittig reaction. 

To facilitate the use of p-amino-aldehydes or -alcohols, obtained through asymmetric Mannich reactions, List et al. provided a procedure to use N-Boc-protected, preformed imines (21, 22) (Scheme 5.13a). While this method requires the formation of the imines, it provides products that can be deprotected under mild conditions, as compared to the widely used and robust PMB-protection in these reactions. Even acetaldehyde is applicable as aldehyde source (Scheme 5.13b). The p-amino-aldehydes (23, 24) obtained from this transformation are extremely valuable building blocks in organic synthesis, making this discovery one of the most useful applications of proline catalysis to date. 

Enolates are powerful carbon nucleophiles and addition of enolates to carbonyl groups (aldol reactions) serve as a useful method for C-C bond formation. The Mukaiyama aldol reactions involving fluoride ion-promoted addition of silyl enolates to aldehydes are very popular and are frequently employed in the construction of carbon skeletons in organic synthesis [ 1 ]. The Mukaiyama aldol reaction with the silyl enol ether of cyclohexanone and 4-bromobenzaldehyde can be performed based on the electroosmotic flow (EOF) technique with a four-chaimel microstructured flow reactor (charmel dimensions 100 x 50pm). The reactor was prepared using a standard fabrication procedure developed at the University of Hull [2, 3]. Based on GC-MS analysis, quantitative conversion of the starting material was achieved in 20 min, whereas in the case with a traditional batch system a quantitative yield was obtained only when an extended reaction time of 24 h was employed (Figure 5.1). 

Aldehydes and ketones have a central role in organic synthesis, and efficient procedures for their preparation are of great importance. Such compounds are synthesized in a number of ways, including hydration or hydroboration-oxidation of alkynes (Eqs. 16.10 and 16.11, respectively, and Chap. 11) and reaction of carboxylic acids or their derivatives with organometallic reagents or reducing agents... 

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