Dihydroxyl aldehyde

The hydroxyalkoxy radicals formed in pathway (k) can take place isomerization by intramolecular shift of H-atom via a six-membered ring as in the case of the alkoxy radical in the previous paragraph. Dihydroxyl aldehyde is then formed in pathways (q), (r), (s) though dihydroxyl radicals which has two OH groups in a molecule. The formation of dihydroxyl aldehyde has been confirmed in the laboratory experiment, and the yield of dihydroxyl aldehyde (3,4-dihydroxyl butanal) is 0.04 for 1-butene but it is as high as 0.6 for 1-octene (Kwok et al. 1996b). Under the low NOx concentrations, a part of hydroxyperoxy radicals react with HO2, and is known to produce hydroxyhydroperoxy butane (pathways (f), (m)) (Hatakeyama et al. 1995 Tuazon et al. 1998). 

Scheme 20. Synthesis of aldehyde 68 the diastereoselective dihydroxylation of 82 and synthesis of 87.

Alternatively, epoxides can be formed with concomitant formation of a C-C bond. Reactions between aldehydes and various carbon nucleophiles are an efficient route to epoxides, although the cis. trans selectivity can be problematic (see Section 9.1.4). Kinetic resolution (see Section 9.1.5.2) or dihydroxylation with sequential ring-closure to epoxides (see Section 9.1.1.3) can be employed when asymmetric epoxidation methods are unsatisfactory. 

Previous syntheses of terminal alkynes from aldehydes employed Wittig methodology with phosphonium ylides and phosphonates. 6 7 The DuPont procedure circumvents the use of phosphorus compounds by using lithiated dichloromethane as the source of the terminal carbon. The intermediate lithioalkyne 4 can be quenched with water to provide the terminal alkyne or with various electrophiles, as in the present case, to yield propargylic alcohols, alkynylsilanes, or internal alkynes. Enantioenriched terminal alkynylcarbinols can also be prepared from allylic alcohols by Sharpless epoxidation and subsequent basic elimination of the derived chloro- or bromomethyl epoxide (eq 5). A related method entails Sharpless asymmetric dihydroxylation of an allylic chloride and base treatment of the acetonide derivative.8 In these approaches the product and starting material contain the same number of carbons. 

Entry 10 was used in conjunction with dihydroxylation in the enantiospecific synthesis of polyols. Entry 11 illustrates the use of SnCl2 with a protected polypropionate. Entries 12 and 13 result in the formation of lactones, after MgBr2-catalyzed additions to heterocyclic aldehyde having ester substituents. The stereochemistry of both of these reactions is consistent with approach to a chelate involving the aldehyde oxygen and oxazoline oxygen. 

For this purpose, the chiral acid (R)-(-)-22 was chosen as the starting material and converted to the spirolactam 25. Condensation with benzylamine followed by catalytic dihydroxylation and oxidation gave aldehyde 23. 

In studies directed toward the total synthesis of tedanolide [38], the addition of y-substituted ketene acetal 60 to aldehyde 84 generated unsaturated ester 85 in 62% yield (Scheme 30). The resulting double bond could be further functionalized by applying Sharpless asymmetric dihydroxylation conditions. Hence diol 86, which represents the mismatched case due to unfavorable... 

However, oxidation processes like epoxidation or dihydroxylation reactions are important transformations in solid support chemistry, because they allow the synthesis of ketones [226], aldehydes [227, 228] and even sulfoxides and sulfones [229]. 

Abstract This chapter covers one of the most important areas of Ru-catalysed oxidative chemistry. First, alkene oxidations are covered in which the double bond is not cleaved (3.1) epoxidation, cis-dihydroxylation, ketohydroxylation and miscellaneous non-cleavage reactions follow. The second section (3.2) concerns reactions in which C=C bond cleavage does occur (oxidation of alkenes to aldehydes, ketones or carboxylic acids), followed by a short survey of other alkene cleavage oxidations. Section 3.3 covers arene oxidations, and finally, in section 3.4, the corresponding topics for aUcyne oxidations are considered, most being cleavage reactions. 

In the ensuing discussion we consider first of all those oxidations which do not involve cleavage of the C=C bond (epoxidation, Section 3.1, c/x-dihydroxylation 3.1.2 and ketohydroxylation 3.1.3, other non-cleavage oxidations 3.1.3.4). Cleavage reactions follow in 3.2 with formation of aldehydes or ketones (3.2.1) and acids (3.2.2). 

Stilbene diols such as 3 are gaining prominence both as synthetic intermediates and as effective chiral auxiliaries. While the diols can be prepared in high by Sharpless dihydroxylation, it would be even more practical to prepare them by direct asymmetric pinacol coupling. N. N. Joshi of the National Chemical Laboratory in Pune reports (J. Org. Chem. 68 5668,2003) that 10 mol % of the inexpensive Ti salen complex 2 is sufficient to effect highly enantioselective and diastereoselective pinacol coupling of a variety of aromatic aldehydes. Most of the product diols are brought to >99% by a single recrystallization. 

Important extensions of proline catalysis in direct aldol reactions were also reported. Pioneering work by List and co-workers demonstrated that hydroxy-acetone (24) effectively serves as a donor substrate to afford anfi-l,2-diol 25 with excellent enantioselectivity (Scheme 11) [24]. The method represents the first catalytic asymmetric synthesis of anf/-l,2-diols and complements the asymmetric dihydroxylation developed by Sharpless and other researchers (described in Chap. 20). Barbas utilized proline to catalyze asymmetric self-aldoli-zation of acetaldehyde [25]. Jorgensen reported the cross aldol reaction of aldehydes and activated ketones like diethyl ketomalonate, in which the aldehyde... 

Oxidative cleavage of the olefin is accomplished by the method of ijemieux-Johnson.12 The process begins with dihydroxylation of the double bond using osmium tetroxide (see Chapter 3)T leading to a cis diol and osmium(VI) oxide. The added periodate has two functions first, it reoxidizes the osmium(VI) species to os-mium(VIII), but it also cleaves the glycol oxidatively to an aldehyde. This is the reason for utilizing several equivalents of periodate. The periodate is in turn reduced from the +VH to the +V oxidation state. 

The diol (43) obtained from dihydroxylation of acrolein benzene-1,2-dimethanol acetal (entry 11) is a masked glyceraldebyde and has the potential to be a very useful synthon. Although the enantiomeric purity of the crude diol formed in this reaction is 84% ee, one recrystallization from ethyl acetate improves it to 97% ee in 55% recovery yield. The masked glyceraldehyde 43 is converted via the tosylate 44 to the masked glycidaldehyde 45 in an overall yield of 85%. Both these masked aldehydes are superior to the free aldehydes in terms of handling ease, stability, and safety. The aldehydes can be released from the acetal under the mild conditions of catalytic hydrogenolysis [45]. 

In the dihydroxylation of cyclohexene by Me3N+—O-, catalysed by OsC>4, aromatic amines and aliphatic chelating (TMEDA) or bridging (DABCO, hexamine) amines were found to retard the oxidation, owing to the formation of amine adducts of the dioxomonoglycolatoosmium(VI) ester intermediates, which are more resistant to the further oxidation required for product formation.98 Alkenes derived from Gamer s aldehyde, A-Boc-/V,0-acctonide of the aldehyde of L-serine, may be dihydroxylated by OsC>4 with excellent selectivities that may be explained by A1,3 strain.99... 

Os04-mediated dihydroxylation of 59 followed by an oxidative cleavage of the formed diol with NaI04 gave the aldehyde, which was decarbonylated with RhCl(PPh3)3 to yield 8-methyl derivative 60 (06OBC1587). Wacker oxidation of 59 provided 8-(2-oxopropyl) derivative 61. 

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