Aldehydes, addition derivatives

Table 3. (4-Hydroxy-3-methvl-l-alkenyl) Carbamodithioates, Carbamothioates, and Carbamates by Aldehyde Addition to the Respective 2-Alkcnyllithium Derivatives...

Enynes 71 react with aldehydes 61 in the presence of the [Ni(COD)J/SIPr catalytic system to afford two distinct products 72 and 73 (Scheme 5.20) [20b], The enone 72 is derived from aldehyde addition with the alkyne moiety while the adduct 73 arises from the aldehyde addition with the alkene moiety. The product distribution is dependent on the substituent on either the alkyne or alkene moieties. The reaction between 71 and ketones 74 led to the unprecedented formation of pyrans 75 (Scheme 5.20). The reaction showed to be highly regioselective in aU the cases, the carbonyl carbon was bound to the olefin. 

The reaction of these aldehydes, derived from periodate oxidation, with carbonyl reagents has also been investigated. Studies 147 148 were made on oxidized laminarin, a (1 —> 3)-linked polysaccharide, in which only the terminal residues had been oxidized. The addition of phenylhydrazine acetate detached the remainder of the terminal residue as glyoxal phenyl-osazone. When the aldehydic compounds derived from the periodate oxidation of raffinose and trehalose818a were reacted with p-nitrophenylhydrazine, the authors were surprised to find that one molecule of oxidized raffinose, containing six aldehydic functions, reacts with only three molecules of the reagent, and that the four aldehydic functions of the oxidized trehalose molecule react with only two. The reactions of periodate-oxidized carbo-... 

This system also worked well in ionic liquids.518 Li etal. found silver-phosphine complexes to promote aldehyde-alkyne coupling in water. When triphenylphosphinesilver chloride was used as a catalyst in water, the only detected product was the aldehyde addition product instead of the adduct derived from imine (Scheme 111).519... 

Closely related to both allyl carbenoids and the allenyl carbenoids discussed above, propargyl carbenoids 101 are readily generated in situ and insert into zirconacycles to afford species 102 (Scheme 3.27), which are closely related to species 84 derived from allenyl carbenoids [65], Protonation affords a mixture of allene and alkyne products, but the Lewis acid assisted addition of aldehydes is regioselective and affords the homopropargylic alcohol products 103 in high yield. Bicydic zirconacyclopentenes react similarly, but there is little diastereocontrol from the ring junction to the newly formed stereocenters. The r 3-propargyl complexes derived from saturated zirconacycles are inert towards aldehyde addition. 

Two aldehydic nucleotide derivatives have found use as affinity labels. The magnesium salt of (64), formed by oxidation of ATP with periodate, is a competitive inhibitor of pyruvate carboxylase with respect to [Mg. ATP2-],100 and (65), obtained from the / -anomer of 5-formyluridine-5 -triphosphate on treatment with alkali, is a non-competitive and reversible inhibitor of DNA-dependent RNA polymerase from E. coli.101 In each case, addition of borohydride gives stoicheiometric covalent linkage of the nucleotide to the enzyme, with irreversible inactivation. It is thought that condensation with lysine occurs to give a Schiff s base intermediate, which undergoes subsequent reduction. 

Dihydro derivatives are readily formed in reactions with aldehydes and ketones, and aldehyde addition products can be dehydrogenated to the fully conjugated heterocycles <1981RCR816, 1995AQ151>. In a new procedure, palladium iodide-catalyzed carbonylation of 1,8-naphthalenediamine 918 gave 2(l//)-perimidinone 921 in 91% yield <2004JOC4741>. 

In the case of aldehyde imines derived from 1-phenyl-1-ethanamine optimum enantioselec-tivities (70 % ee) and good yields were achieved using magnesium azaenolates and HMPA as additive (see Table 5)6. 

Schwartz (1972) also noted the detection of about 70 glycerol-l-alkyl ethers in milk fat. Saturated ethers, both odd and even from C-10 through C-18, were found, with traces of ethers up to C-25 present. Fifty-five unsaturated ethers were separated, but only the A-9, A-9, 12, and A-9, 12,15 compounds were tentatively identified. In addition, Schwartz isolated over 50 bound aldehydes probably derived from the glycerol-l-alkenyl ethers (phosphorus free). 

In 1997, Kobayashi and colleagues reported the first truly catalytic enantioselective Mannich-type reactions of aldimines 24 with silyl enolates 37 using a novel chiral zirconium catalyst 38 prepared from zirconium (IV) fert-butoxide, 2 equivalents of (R)-6,6 -dibromo-l,l -bi-2-naphthol, and N-methylimidazole (Scheme 13) [27, 28], In addition to imines derived from aromatic aldehydes, those derived from heterocyclic aldehydes also worked well in this reaction, and good to high yields and enantiomeric excess were obtained. The hydroxy group of the 2-hydroxyphenylimine moiety, which coordinates to the zirconium as a bidentate ligand, is essential to obtain high selectivity in this method. 

Germenes react with various reagents as shown in Scheme 20le,lp 51. For example, addition of methanol affords a methoxygermane. In the reactions with ketones and aldehydes oxagermetane derivatives are obtained. The reactions of a,/ -unsaturated aldehydes and ketones afford [4+2]cycloadducts. These reactions proceed regiospecifically, according to the Ges+=Cs polarity. 

Enantioselective Addition of Diethylzinc to Aldehydes. Oxazaborolidines derived from ephedrine have been used to catalyze the addition of Diethylzinc to aldehydes (eq 13). Both... 

When Lewis acids such as SnCU and TiCU are used to promote additions of allylic trialkyltin reagents to aldehydes several reaction outcomes are possible, depending on stoichiometry and the mode of addition. If the Lewis acid is added to the aldehyde followed by the allylic stannane, the typical product (syn for crotylstannanes) derived from an acyclic transition state is formed. If, however, the stannane and Lewis acid are premixed and left to equilibrate, metathesis can occur forming the allylic halome-tal compound which reacts with the subsequently added aldehyde to give products (anti for crotyl) consistent with a cyclic transition state (Eq. 22). The initially formed allylic halostannane gives rise to the linear adduct, but if aldehyde addition is delayed, this initial secondary allylic metal halide can equilibrate to the primary isomer which then reacts with the aldehyde to afford the branched product. 

These reactions proceed by initial Se2 addition of SnCLt to the allylic stannane to yield an intermediate trichlorostannane (Fig. 13). This trichlorostannane derives stability by coordination with the adjacent benzyloxy oxygen. Aldehyde addition proceeds through a cyclic transition state in which the allyhc substituent adopts an axial orientation to minimize interactions with the tin substituents and to maintain effective coordination with the adjacent benzyloxy oxygen. As a result the (Z)-homoallylic alcohol adduct is highly favored. 

The active aldehydes are derived from the reaction of 3-benzylthiazolium salts with o-tolualdehyde in the presence of DBU (l,8-diazabicyclo[5.4.0]undec-7-ene) via deprotonation of thiazolium salts, addition of the aldehyde and deprotonation of the adduct as shown in Scheme 33 [364], The anionic form of active aldehydes in Scheme 33 is confirmed by the direct detection of the one-electron oxidized species with use of ESR [364]. From the linewidth variations of the ESR spectra of the oxidized active aldehyde radicals were determined the rate constants [(5-7) x 10 s ] and the corresponding small reorganization energies (A = 12-13... 

A number of addition derivatives may be used in the identification of the carbonyl compounds. Of these the crystalline derivatives formed with phenylhydrazine, C6H6NHNH2, and hydroxylamine, NH2OH, are the most important. The products formed with phenylhydrazine are called phenyUiydrazones, and have the general formula, RRiC=NNHC jls. The products formed with hydroxylamine are called oximes, and have the general formula, RRiC=NOH. Other crystalline addition compounds are formed with sodium bisulfite by aldehydes, and by those ketones which contain a methyl group. The addition compounds with ammonia, except in the case of acetaldehyde and a few other carbonyl compounds, are complex products. 

As part of a series of studies on the use of BINOL-Ti(IV) complex 53 as a catalyst in a number of C-C bond-forming reactions, Mikami has reported the aldol addition reactions of thioacetate-derived silyl ketene acetals 55, 56 to a collection of highly functionalized aldehydes (Eq. (8.13)) [28]. As little as 5 mol% of the catalyst mediates the addition reaction and furnishes adducts 57 in excellent yields and up to 96% ee. One of the noteworthy features of the Mikami process is the fact that aldehyde substrates containing polar substituents can be successfully employed, a feature exhibited by few other Lewis-acid-catalyzed aldehyde addition reactions. 

A great majority of the catalytic aldol processes that have been developed over the last two decades involve Lewis acids derived from complexes of titanium, boron, tin, and, more recently, copper as well as silver. A recent, exciting area of rapid development for aldehyde addition reactions is represented by the catalytic aldol methods that utilize soft-metal and lanthanide coordination complexes which mediate addition reactions through metalloenolate intermediates. 

Stable pentacoordinated allylsiliconates have been employed in aldehyde addition reactions. These reagents require no activation by Lewis acids or Lewis bases, but have found only limited applications in synthesis to date. The use of these agents in addition to aldehydes was first described in 1987 by Corriu [59] and Hosomi [60] and by Kira and Sakurai [61] in 1988. In these reactions, the addition of a catechol or 2,2 -biphenol-derived allylsiliconate to an achiral aldehyde led to the highly regio- and stereoselective formation of homoallylic alcohols. For example, the addition of the catechol-derived 2-butenylsiliconate 81 (90/10 E Z) provided a diastereomeric mixture of homoallylic alcohols 74 and 75 in a 90/10 ratio (Scheme 10-33) [60c]. 

Stannanes and silanes may act as carbanion derivatives that can be activated with suitable Lewis adds. Thus, as shown by Cossy et al. [440], allylstannanes may be transmetalated with InCU to generate allylindium derivatives in situ. The latter can react with aldehydes to give mixtures of syn and anti adducts (with aromatic aldehydes and 2-buten-l-al). With aliphatic aldehydes, only the anti adducts are observed. The authors concluded that product mixtures were partly caused by the kinetic formation of a mixture of indium (Z)- and ( )-allyl esters prior to the condensation. They then allowed the indium species to equilibrate prior to the aldehyde addition and obtained mainly anti adducts (627, 628) (Scheme 130). 

Syn selective aldol additions of titanated aldehyde hydrazones and ketone hydrazones have been reported by Reetz. The observed syn selectivity parallels the syn selectivity seen in titanium ketone eno-iates, and the intermediate titanium aldehyde hydrazone derivatives were seen to have ( )c—c geometry (equation 17). 

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