Hydroxy aldehydes, alkylation

In Entry 5, the carbanion-stabilizing ability of the sulfonyl group enables lithiation and is then reductively removed after alkylation. The reagent in Entry 6 is prepared by dilithiation of allyl hydrosulfide using n-bulyl lithium. After nucleophilic addition and S-alkylation, a masked aldehyde is present in the form of a vinyl thioether. Entry 7 uses the epoxidation of a vinyl silane to form a 7-hydroxy aldehyde masked as a cyclic acetal. Entries 8 and 9 use nucleophilic cuprate reagents to introduce alkyl groups containing aldehydes masked as acetals. 

Since ketone R)-16 was prepared in a non-selective way when an achiral imino enolate was alkylated, it was considered whether alkylation of chiral enolates, such as that of oxazoline 18, with benzyl bromide 14, would provide stereoselective access to the corresponding alkylation product 19 with R-configuration at C(8) (Scheme 4). Indeed, alkylation of 18 with 14 gave the biaryl 19 and its diastereoisomer almost quantitatively, in a 14 1 ratio. However, reductive hydrolysis using the sequence 1. MeOTf, 2. NaBH4, and 3. H30", afforded hydroxy aldehyde 20 in 25% yield at best. Furthermore, partial epimerization at C(8) occurred (dr 7.7 1). An alternative route, using chiral hydrazones, was even less successful. 

Reversible Modifications. Reversibility of a modification is frequently a desired characteristic in order to regain the protein in its original native form. A variety of methods (I) is available for this purpose. Sometimes a further intermediate modification is necessary as used recently in the reductive alkylation of amino groups with an a-hydroxy aldehyde or ketone and subsequent removal of the hydroxyalkyl group by periodate cleavage (85) (see Figure 18). 

The alkylation of SAMP/RAMP hydrazones with heteroelectrophiles leads to enantiomerically pure a-silyl aldehydes and ketones (eq 15), a-sulfenyl aldehydes and ketones (eq 16), and a-hydroxy aldehydes and ketones (eq 17). ... 

The third formal total synthesis (Scheme 1.30) to arise from Tsuji s laboratories appears to be a combination of the previous two. The carbonylation reaction between iodide 151 and alcohol 155 gave the expected ester 156 (70%). Intermolecular benzylic alkylation with protected 4-iodobutanol then gave 157 in 90% yield. Hydroxy aldehyde 158 was then obtained in 75% yield following... 

Diese Aldehyd-Synthesen basieren auf dem Prinzip der Meyers-Aldehydsynthese aus 1,3-Oxazinen (s.S. 384). Ausgehend von 2,4-Dimethyl-1,3-thiazol386 oder 2-Me-thyl-4,5-dihydro-l,3-thiazol413 werden 3-Hydroxy-, 2-Alkyl- und 2,2-Dial-kyl-alkanale hergestellt ... 

In addition to phenols, naphthols, their alkyl derivatives and the heterocyclic compounds mentioned above, a large variety of substituted monocyclic as well as condensed phenols have been subjected to the Reimer-Tiemann reaction. Although with a few exceptions the yields are only moderate, the facile reaction conditions, at least on a laboratory scale, have assured the reaction a permanent place among the variety of methods by which an aldehyde group can be attached to an aromatic nucleus. For example, phenolphthalein (1) has been formylated under standard Reimer-Tiemann conditions by van Kampen to yield the o-hydroxy aldehyde in 59% yield (equation 5)."... 

The desired synthon, acetonide 520, is prepared from carbonate 517 by treatment with acetone under acidic conditions. Alkylation of bicyclic lactone 521 with 520 affords 522 as a single isomer. Reduction of the lactone with DIBAL produces an equilibrium mixture of lactol and hydroxy aldehyde 523. Oxidation of the ally lie alcohol and decarbonylation with Wilkinson s catalyst furnishes the crucial enone intermediate 524 common to both natural products. 

Ortho/para directing Meta directing Amino, hydroxy (strongly) alkyl, alkoxy, amido, aryl (weakly) None Halogens Nitro, ammonium, sulfonium (strongly) aldehydes, ketones, acids, (weakly) esters, carboxamides... 

Several homogeneous metal catalysts related to hydroformylation based on Co, Rh, Pt, Pd, or Ir are able to open epoxides (oxiranes) [1]. In the 1980s, Milstein and Bergman [2] could intercept some metal alkyl enolates derived from this reaction. Such complexes can undergo CO insertion to give metal-acyl complexes. By final hydrogenolysis, P-hydroxy aldehydes result. 

Our strategy for the synthesis of (+)-dactylolide (2.217) is outlined in Scheme 2.69. We envisioned that the 20-membered macrolactone in 2.332 could be constructed by intramolecular iV-heterocyclic carbene (NHC)-catalyzed oxidative macrolactonization of co-hydroxy aldehyde 2.333. Intramolecular NHC-catalyzed oxidative esterification reactions have been recognized as an attractive tool and rapidly growing area in the synthetic community. Indeed, several examples of these reactions have recently been reported [208-216], which clearly provide a new opportunity for the development of catalytic acyl transfer agents in macrolactonization reactions of co-hydroxy aldehydes in the presence of oxidants. The substrate for the macrolactonization reaction would be derived firom the cyanohydrin alkylation of 2,6-dr-tetrahydropyran enal 2.335 with dienyl chloride 2.334. 2,6 -di-tetrahydropyran enal would in turn be constructed by employing the 1,6-oxa conjugate addition reaction of co-hydroxy 2,4-dienal 2.336. Despite the... 

Alkylation of aldol type educts, e.g., /3-hydroxy esters, using LDA and alkyl halides leads stereoselectively to erythro substitution. The erythro threo ratio of the products is of the order of 95 5. Allylic and benzylic bromides can also be used. The allyl groups can later be ozonolysed to gjve aldehydes, and many interesting oligofunctional products with two adjacent chiral centres become available from chiral aldol type educts (G. Prater, 1984 D. Seebach, 1984 see also M. Nakatsuka, 1990, p. 5586). 

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