A-Phenylseleno aldehydes

Rearrangement of 2-kydroxy-3-trimethylsilylpropyt selenides (2). These selenides (2), prepared as shown from a-phenylseleno aldehydes (1), rearrange in the presence of SnCl2, usually to allylic selenides.1... 

Phenylpropane-l-ol, 438 Phenyl propargyl seienide, 365 Phenylselenoacetaldehyde, 365-366 a-Phenylseleno aldehydes, 25, 29 up-Phenylselenocarboxylic acids, 496 Phenylselenoetherification, 26 a-Phenylseleno ketals, 29 a-Phenylseleno ketones, 25 Phenylselenolactones, 26 Phenylselenomethyl ketones, 365-366 N -Phen y Iselenopht halim ide, 366-367 N-Phenylselenosuccinimide, 366-367 Phenylselenotrimethylsilane, 373 Q -Phenylseleno-Q ,/3-unsaTurated ketones, 28... 

OL-PhenylseUno aldehydes. Oxidation of allylic f-butyldimethylsilyl ethers remits in a-phenylseleno aldehydes, which on desilylation give a-phenylseleno-a,/9-unsaturated enals. A typical example is formulated in equation (I). 

Allyl methyl ethers of the type shown in equation (II) are also oxidized to a-phenylseleno aldehydes. 

A new convenient method of synthesis of a-phenylseleno-aldehydes and -ketones involves the reaction of phenylselenyl bromide and enol silyl ethers. ... 

Dicarbonyl Compounds.— 2,3-Dihydroxy-l,4-dioxan functions as a stable synthetic equivalent to glyoxal, particularly in the synthesis of a variety of heterocycles. The dioxan overcomes the prerequisite preparation of pure glyoxal immediately prior to its use (because of its tendency to polymerize) and offers an alternative available for reaction under non-aqueous conditions. Monoprotected a-keto-aldehydes are seldom available by selective derivatization of the parent dicarbonyl compound. However, 1,1,2,2-tetramethoxy-alkanes, readily prepared from a,a-dichloro-aldehydes, undergo regioselective hydrolysis to give l,l-dimethoxyalkan-2-ones. The sequence from the dichloro-aldehyde may be carried out without isolation of the tetramethoxylated intermediate. a,a-Bis(phenylseleneno)-aldehydes may be prepared from aldehydes or the intermediate a-(phenylseleno)-aldehyde by treatment with morpholinophenyl-selenenamide. a-(Arylseleno)-ap-unsaturated aldehydes result from the electrochemical oxidation of 3-hydroxyalkynes in the presence of a diaryl diselenide [equation (42)]. Treatment of a,a -dibromo-ketones with primary... 

One of the standard methods for the preparation of aldehydes involves the reduction of acid halides. A variety of stoichiometric reducing systems are available for this transfomiation, which include NaAlH(OBu-r)3, LiAlHfOBu-O.i, NaBHfOMe). Catalytic hydrogenation with H2 and Pd on carbon is also a popular method. In contrast, methods based on the radical reduction of acyl halides are synthetically less important. Radical reduction methods involve generation and subsequent hydrogen abstraction as key steps, which is complicated by decarbonylation of the intermediate acyl radicals. The first example in Scheme 4-1 shows that this competitive reaction is temperature dependent, where an acyl radical is generated from an acyl phenyl selenide via the abstraction of a phenylseleno group by tributyltin radical [5]. 

In the synthesis of aspyrone (994), an antibiotic isolated from the culture broth of Aspergillus species, lactaldehyde 990 supplies the asymmetric centers of the epoxide in the side chain (Scheme 134). The molecule is assembled convergently by addition of the lithium enolate of D-rhamnose-derived a-phenylseleno- -lactone 991 to aldehyde 990. After an initial aldol-type reaction, the intermediate alkoxide displaces tosylate to provide epoxide 992 with >99.8% stereoselectivity. Peroxide-induced elimination of phenylselenide furnishes TBS-protected aspyrone 993 in 61% overall yield from 990. 

Phenylpropargyl selenide is converted into a-phenylseleno-a/S-unsaturated aldehydes and ketones by a reaction sequence outlined in Scheme 58. The corresponding selenium-free enone can be obtained by using excess hydrogen peroxide in methanol as the oxidant in the final step. ... 

The same enamine activation strategy was later applied to develop the first successful catalytic asymmetric a-selenylation of aldehydes by Melchiorre, Marini, and co-workers [79]. Aldehydes were reacted with A-(phenylseleno)phthalimide in the presence of 5 mol% loading of O-TMS diaryl prolinol 17a and / -N02C6H5C02H as co-catalyst. Selenyl alcohols were selectively recovered, after in situ reduction, in high yield and excellent enantioselectivity (Scheme 14.28). 

The a-selenylation of carbonyl compounds is in its first preliminary stage. In fact, there are only few examples, in which different aldehydes reacted with A -(phenylseleno)phthalimide 78 to yield the expected a-functionalized aldehyde in the presence of 4-imidazolidinone 58, with very moderated results. This result could be slightly improved by the use of 2-(tosylaminomethyl)pyrrolidine 21b (Ar=4-MeCgH ) up to 60% ee [112]. A similar reaction using cyclohexanone gave the expected a-seleno cyclohexanone with a good chemical yield but very low enantioselectivity (88%, 18% ee). 

Alternatively, a,a-diaryl prolinol catalysts 22 (5 mol%) in combination with /1-nitrobenzoic acid or catalyst 15a (20 mol%) could be used to promote the a-selenenylation of aldehydes using A-(phenylseleno)phtalimides as electrophile [113]. For this reaction, toluene was the solvent of choice and the in situ reduction of the obtained product to the corresponding alcohol was needed in order to preserve the achieved levels of enantioselectivities (Scheme 4.15). A wide range of aldehydes, including alkyl, alkenyl and heterosubstituted aldehydes were suitable substrates, affording the expected products 79 with excellent enantioselectivities. 

Precursor y-halogeno alcohols are frequently prepared by the classic sequence of addition of hydrogen halide to a,/3-unsaturated aldehydes, ketones, acids or esters, followed by Grignard reaction or hydride reduction. Recently a novel and general synthesis of 3-methoxyoxetanes from 3-phenylseleno-2-propenal was reported. This method comprises a sequence of Grignard addition to the aldehyde function, treatment with two equivalents of MCPBA, and then reaction with methanolic sodium hydroxide (equation 78) (80JOC4063). 

From a- or 0- substituted aldehydes or ketones by elimination reactions Benzeneselenenyl trichloride, 27 Methanesulfonyl chloride-4-Di-methylaminopyridine, 176 9-(Phenylseleno)-9-borabicyclo-[3.3.1]nonane, 245 By oxidation of allylic substrates Pyridinium chlorochromate-Benzo-triazole, 262 By other methods Alumina, 14... 

Selenenamides (23) are obtained by the substitution of selenenyl halides with amines or by the metathesis of the former compounds with Af-silylamines. N-(Phenylseleno)phthalimide (24) is similarly obtained using potassium phthalimide (Scheme 10). These compounds can be isolated but are prone to hydrolyze when exposed to moisture. Selenenamides react with aldehydes or jS-dicarbonyl compounds to afford a-seleno derivatives (as in the process shown in equation 11), and add to activated double and triple bonds, as in the example in equation (19). The imide (24) is a useful alternative to PhSeCl in various selenenylation reactions, and to ArSeCN in the conversion of alcohols and carboxylic acids to selenides and selenoesters (8), as shown in Scheme 3. 

In a series of elegant studies, Paquette and coworkers demonstrated the potential of the Claisen rearrangement for the stereocontrolled total synthesis of natural products. Dehydrative coupling of (2)-3-(trimethylsilyl)-2-propen-l-ol with cyclohexanone (51) under Kuwajima s conditions, followed by rearrangement of enol ether (52) in decalin, led in excellent stereoselectivity (>99 1) to aldehyde (53 Scheme 8). Concise construction of the eight-membered core of acetoxycrenulidine was achieved by intramolecular phenylseleno etherification of lactone (54), introduction of the exocyclic vinyl ether double bond by selenoxide elimination and subsequent Claisen rearrangement (Scheme 9, 66% from 54). ... 

C, 1-phenylseleno- and 1-methylseleno-l-alkenyllithiums in almost quantitative yields (Scheme 101). The stereochemistry of the reaction is not well defined and the only available results are those concerning the stereochemistry of the compounds resulting from further reaction of these organo-metallics with electrophiles. Both stereoisomers are formed if the methylselenoalkenyllithium is hydrolyzed or reac with an aldehyde or a ketone, whereas only one stereoisomer of an a, -un-saturat carbonyl compound is found from l-methylseleno l-alkenyllithiums and and from the... 

P-Hydroxy selenides are conveniently prepared from epoxides by treatment with sodium phenylse-lenide (Scheme 32) and by the addition of benzeneselenenic acid and its derivatives to alkenes (Scheme 33), - -" although in some cases these reactions are not regioselective. Useful phenylseleno -etherification and -lactonization reactions have been developed which can be regioselective (equation 42 and Schemes 34 and 35). -" " Selenide- and selenoxide-stabilized carbanions have been used in addition reactions with aldehydes and ketones, - and the reduction of a-seleno ketones also provides a route to P-hydroxy selenides. ... 

Photocleavage of benzyl-S bonds appears to proceed neither by an electron transfer pathway nor with participation of an exciplex. A meta effect seems to operate in these reactions as evidenced by the influence of 3-methoxy and of 3-cyano substituents on the efficiency of the cleavage process. Photolysis of 1,2-bis(phenoxymethyl)-, l,2-bis(phenylthiomethyl)-, and l,2-bis(phenylseleno-methyl)benzene induces a two-photon process to give o-quinonedimethane, which in the presence of dienophiles undergoes a cycloaddition reaction, and 4,8,10-trithiadibenzo[cd,ij]azulene 8-oxides gives the corresponding aldehydes and ketones together with 4,8,9-trithiacyclopenta[def]phenanthrene. The two... 

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