1 aldehyde protection

To make (18), we must reduce the ester in the presence of the aldehyde protection is necessary and an acetal the obvious way. 

In general, the methods for protection and deprotection of carboxylic acids and esters are not as convenient as for alcohols, aldehydes, and ketones. It is therefore common to carry potential carboxylic acids through synthetic schemes in the form of protected primary alcohols or aldehydes. The carboxylic acid can then be formed at a late stage in the synthesis by an appropriate oxidation. This strategy allows one to utilize the wider variety of alcohol and aldehyde protective groups indirectly for carboxylic acid protection. 

The specific glove and protection requirements are Chemical type Is aldehyde Protection time requirement In minutes Is 200 Tactlllty requirement Is moderate tactile... 

Since a-branched aldehydes gave rather higher asymmetric induction (Scheme 6.166), Nagasawa et al. extended the biphasic strategy to the diastereoselective Henry reaction of nitromethane with enantiomerically pure (S)-configured N,N -dibenzyl protected a-amino aldehydes and a-hydroxy aldehydes protected as silyl ethers. The screening reaction (Scheme 6.169) demonstrated a match/mismatch... 

As with aldehydes, production of ketones by nonredox processes is not a common synthetic approach. Ketone derivatives having the same oxidation level are usually produced from ketones themselves. Several examples of enol and acetal ketone derivatives are shown below. All are prepared from ketones, all can be readily hydrolyzed back to the ketone in the presence of acidic water, and, with the exception of vinyl acetates, all are very stable to strong bases and nucleophiles. Acetals are often used as ketone (and aldehyde) protecting groups while enol derivatives are versatile synthetic intermediates. 

Chiral pyrrolidine derivatives, proline, and amino acid-derived imidazolidinones mediate the asymmetric epoxidation of ,/i-unsalurated aldehydes. Protected a,a-diphenyl-2-prolinol catalyses the asymmetric formation of 2-epoxyaldehydes, with hydrogen peroxide or sodium percarbonate as the oxygen sources, with 81-95% conversion with up to 96 4 dr and 98% ee.204... 

Ladlow and coworkers recently developed an acid-labile fluorous benz-aldehyde protecting group 43 to facilitate the parallel synthesis of sulfonamides 44 (Scheme 25) [56]. The Suzuki coupling reaction was conducted under microwave irradiation. All the intermediates and the final products were purified by F-SPE. 

Synthesis of aldehyde-protected alcohol compound Structure 16a (Scheme 9.13)... 

An alternate approach, the inversion strategy, is useful for the transformation of ketose to aldose products.35 In this procedure mono-protected dialdehydes were allowed to react with DHAP in the presence of an aldolase to generate ketoses. The ketones are then reduced either chemically or enzymatically. When the aldehyde-protecting group is removed, the aldose is revealed.27 36... 

The alkylation of protected cyanohydrin anions constitutes an excellent method for ketone synthesis. Generally the anions are generated from aliphatic or aromatic aldehyde protected cyanohyd with LDA under nitrogen at -78 C. The addition of an alkyl halide produces the protected ketone cyanohydrin. The carbonyl group is then liberated by successive treatment with dilute acid and dilute aqueous base. This method is applicable for the synthesis of buflomedil. ... 

An interesting approach to the central eight-membered ring of ceroplastol I is based on an intramo-lecnlar Homer-Wadsworth-Emmons reaction employing a diethyl 7-formylalkylphosphonate. The C-7 aldehyde, protected as a 1,3-dioxolane, is obtained in 20% yield by a Michael addition of an alkenyllithium to 2-(diethoxyphosphinyl)cyclopentenone in THF at -78°C. Hydrolysis of the acetal nsing HjO and TsOH in reflnxing acetone yields 89% of the phosphonylated ketoaldehyde (Scheme, 5.56). ... 

Rhodium acetate-assisted cyclization (review [3928]) of an aldehyde (protected as an aminoaziridinehydrazone) which also has a lactam in another ring gives a high yield of the azepine. 

Additions to a,3-dialkoxy aldehydes (protected glyceraldehydes) are complicated by the possibility of chelation involving either the a or 3 alkoxy group. With 2,3-0-isopropylideneglyceraldehyde (62 equations 21 and 22) and Znh as catalyst, a preponderance of the 3-chelated complex (63) was obtained with consequent formation of the C-3,C-4 anti compounds as major isomers (Table 13, entries 1-3 Table 14,... 

Deprotection. Aldehydes protected as a-trichloromethylalkyl TBS ethers by reaction with TBS-Cl and ClsCCOONa are recovered by treatment with TBAF in DMF. ... 

Cyclic enediynes. The realization that a number of antitumor antibiotics contain an enediyne core which is essential for their activity has led to extensive methods for synthesis of this ring system. One approach involves an aldol reaction with an acetylenic aldehyde protected as the Co2(CO)6 adduct. Thus the keto aldehyde 1, prepared in five conventional steps from cyclopcntenc-l,3-dione, on treatment with dibutylboron triflate and N(C2H5)y cydizes to 2 in 69% yield. Attempted dccomplexation with N-methyl-... 

Apart from the technical route described to p-apo-8 -carotenal, readily available vitamin A alcohol (Cjo) has served as an intermediate in the form of the phosphonium salt by reaction with the monodiethyl acetal of a Cio dial (ref. 54). The required Cjo monodiethylacetal was obtained (ref.5, p409) by the reaction of the mono aldehyde-protected derivative, the enol ether of methylmalonaldehyde, (C4) with the acetylenic Grignard reagent from trans 3-methyl-2-penten-4-yn-l-ol (C ) followed by acidic dehydration and partial reduction with Lindlar catalyst to give firstly 8-hydroxy-2,6-dimethylocta-2, 4,6-triene-l-al (Cio). Protection of the hydroxyl group by acetylation in pyridine solution with acetyl chloride and formation of the diethyl acetal with ethyl orthoformate followed by hydrolysis of the acetyl group and oxidation afforded the final CIO aldehyde component (D)shown in Scheme 15a. 

The primary alcohol in 133 was protected as the benzoyl ester 134 before removal of the aldehyde-protecting group in order to prevent hemiacetal formation between the Cn-OH and the C2i-aldehyde functions. The indole amine in 134 was tosylated under basic conditions, accompanied by some epimerization occurring at C-20, to produce the epimeric mixture 136. The aldehyde function in 136 was converted to a silyl enol ether, and then a hydroxy group was introduced at the C-20 position by treatment with... 

Conversion of the aldehyde to protected derivatives at the same level of oxidation (such as ketals, oximes, hydrazones) has been long known. A new hydrazone derived from 4-aminothiomorpholine S,S-dioxide has been carefully investigated [134, 138] and some thiazolidine derivatives have been recently evaluated [136]. C-20 thioketals have been recently introduced, which are especially useful as an aldehyde-protecting group when hydrolysis of the acid-labile mycarose is not wanted their synthesis is accomplished by treatment of the aldehyde with diphenyldisulfide and a trialkylphosphine [134, 139]. The aldehyde has also been transformed into ketones with diazoalkanes [134]. 

A similar transformation (Scheme 12) can be achieved by allowing the carbanion derived from a-chloroethyltrimethylsilane to react with an aldehyde or ketone to give the a/3-epoxysilane, which is readily hydrolysed to the methyl ketone. Similarly chloromethyltrimethylsilane provides aldehydes through homologation of ketones and aldehydes. Direct conversion of the intermediate epoxysilanes into the corresponding aldehyde protected as the ketal or dithioketal is also described. ... 

Organotetracarbonylferrates, [RFe(CO)4], continue to find use in organic synthesis. A new synthesis of a-diketones consists of the reaction of aldehydes with alkyl halides and [Fe(CO)s]. The aldehyde, protected as the ethylenedithioacetal, is treated with butyl-lithium and [Fe(CO)s] to generate the acyltetracarbonylferrate (25) which then reacts with the alkyl halide to give the a-diketone in an overall yield of around 60%. [RFe(CO)4] reacts with Michael-type acceptors to give the expected product in about 90% yield [equation (10)]. ... 

Interesting examples for conjugate additions mediated by chiral amines have been described by Alexakis et al. (Scheme 36), who used the nitroalkene 151 as a Michael acceptor in organocatalytic enamine-catalyzed conjugate addition reactions 149, 150, 153). Michael reaction of 151 with propionaldehyde 60 in the presence of the diamine catalyst 152 (15 mol%) gave 153 as a mixture of four diastereomers in good yield. Subsequent aldehyde protection and conversion of the... 

The two halves of the biaryl are constructed by standard chemistry. The upper half (47) is derived from piperonal by nuclear broniination to (46), followed by aldehyde protection as the acetal. As will be seen below, the state of hybridisation of this group is critical to the success of the synthesis. 

---