A reaction with aldehydes

The ylide obtained from (methyl)triphenylphosphonium bromide reacts with morpholine derivatives 597 to give phosphonium salts 598 which upon treatment with -butyllithium are converted to new ylides 599. In a reaction with aldehydes, ylides 599 form iV-(l,3-disubstituted allyl)-morpholines 602 (Scheme 94) <1996AQ138>. Another less common nucleophile that can be used for substitution of the benzotriazolyl moiety in Af-(a-aminoalkyl)benzotriazoles is an adduct of iV-benzylthiazolium salt to an aldehyde which reacts with compounds 597 to produce adducts 600. Under the reaction conditions, refluxing in acetonitrile, salts 600 decompose to liberate aminoketones 601 <1996H(42)273>. 

D-penidllamine can promote the elimination of copper (e.g., in Wilson s disease) and of lead ions. It can be given orally. Two additional uses are cystinu-ria and rheumatoid arthritis. In the former, formation of cystine stones in the urinary tract is prevented because the drug can form a disulfide with cysteine that is readily soluble. In the latter, penicillamine can be used as a basal regimen (p. 320). The therapeutic effect may result in part from a reaction with aldehydes, whereby polymerization of collagen molecules into fibrils is inhibited. Unwanted effects are cutaneous damage (diminished resistance to mechanical stress with a tendency to form blisters), nephrotoxicity, bone marrow depression, and taste disturbances. 

A. Reactions with Aldehydes and Ketones to give Alcohols... 

Cycloaddition of COj with the dimethyl-substituted methylenecyclopropane 75 proceeds smoothly above 100 °C under pressure, yielding the five-membered ring lactone 76. The regiocheraistry of this reaction is different from that of above-mentioned diphenyl-substituted methylenecyclopropanes 66 and 67[61], This allylic lactone 76 is another source of trimethylenemethane when it is treated with Pd(0) catalyst coordinated by dppe in refluxing toluene to generate 77, and its reaction with aldehydes or ketones affords the 3-methylenetetrahy-drofuran derivative 78 as expected for this intermediate. Also, the lactone 76 reacts with a, /3-unsaturated carbonyl compounds. The reaction of coumarin (79) with 76 to give the chroman-2-one derivative 80 is an example[62]. 

Lithiated indoles can be alkylated with primary or allylic halides and they react with aldehydes and ketones by addition to give hydroxyalkyl derivatives. Table 10.1 gives some examples of such reactions. Entry 13 is an example of a reaction with ethylene oxide which introduces a 2-(2-hydroxyethyl) substituent. Entries 14 and 15 illustrate cases of addition to aromatic ketones in which dehydration occurs during the course of the reaction. It is likely that this process occurs through intramolecular transfer of the phenylsulfonyl group. 

Adducts from various quaternary salts have been isolated, in reactions with aldehydes, a-ketoaldehydes, dialkylacylphosphonates and dialkyl-phosphonates, isocyanates, isothiocyanates, and so forth (Scheme 15) (36). The ylid (11) resulting from removal of a Cj proton from 3.4-dimethyl-S-p-hydroxyethylthiazolium iodide by NEtj in DMF gives with phenylisothiocyanate the stable dipolar adduct (12) that has been identified by its NMR spectrum and reactional product, such as acid addition and thiazolidine obtention via NaBH4 reduction (Scheme 16) (35). It must be mentioned that the adduct issued from di-p-tolylcarbodiimide is separated in its halohydrogenated form. An alkaline treatment occasions an easy ring expansion into a 1,4-thiazine derivative (Scheme 17) (35). 

Reactions with Aldehydes and Ketones. The base-catalyzed self-addition of acetaldehyde leads to formation of the dimer, acetaldol [107-89-1/, which can be hydrogenated to form 1,3-butanediol [107-88-0] or dehydrated to form crotonaldehyde [4170-30-3]. Crotonaldehyde can also be made directiy by the vapor-phase condensation of acetaldehyde over a catalyst (53). 

The primary and secondary alcohol functionahties have different reactivities, as exemplified by the slower reaction rate for secondary hydroxyls in the formation of esters from acids and alcohols (8). 1,2-Propylene glycol undergoes most of the typical alcohol reactions, such as reaction with a free acid, acyl hahde, or acid anhydride to form an ester reaction with alkaU metal hydroxide to form metal salts and reaction with aldehydes or ketones to form acetals and ketals (9,10). The most important commercial appHcation of propylene glycol is in the manufacture of polyesters by reaction with a dibasic or polybasic acid. 

Reactions at G-5. The C-5 atom of hydantoins can be considered as an active methylene group, and therefore is a suitable position for base-cataly2ed condensation reactions with aldehydes (44). 2-Thiohydantoins give the reaction more readily than their oxygen counterparts ... 

Poly(vinyl alcohol) participates in chemical reactions in a manner similar to other secondary polyhydric alcohols (82—84). Of greatest commercial importance are reactions with aldehydes to form acetals, such as poly(vinyl butyral) and poly(vinyl formal). 

Other modifications of the polyamines include limited addition of alkylene oxide to yield the corresponding hydroxyalkyl derivatives (225) and cyanoethylation of DETA or TETA, usuaHy by reaction with acrylonitrile [107-13-1/, to give derivatives providing longer pot Hfe and better wetting of glass (226). Also included are ketimines, made by the reaction of EDA with acetone for example. These derivatives can also be hydrogenated, as in the case of the equimolar adducts of DETA and methyl isobutyl ketone [108-10-1] or methyl isoamyl ketone [110-12-3] (221 or used as is to provide moisture cure performance. Mannich bases prepared from a phenol, formaldehyde and a polyamine are also used, such as the hardener prepared from cresol, DETA, and formaldehyde (228). Other modifications of polyamines for use as epoxy hardeners include reaction with aldehydes (229), epoxidized fatty nitriles (230), aromatic monoisocyanates (231), or propylene sulfide [1072-43-1] (232). 

A cyclic malonste derivative (acidic methylene) used in place of malonate in alkylations or reactions with aldehydes... 

Mixtures of anhydrous hydrogen fluoride and tetrahydrofuran are successfully used as fluorinating agents to convert 1,1,2-trifluoro-l-allcen-3-ols, easily prepared from bromotrifluoroethene via lithiation followed by the reaction with aldehydes or ketones, to 1,1,1,2-tetrafluoro-2-alkenes The yields are optimal with a 5 1 ratio of hydrogen fluoride to tetrahydrofuran The fluorination reaction involves a fluonde lon-induced rearrangement (Sf,j2 mechanism) of allylic alcohols [65] (equation 40)... 

A -Chloromethylamine attacks ketones in alkaline solution with formation of oxaziranes with cyclohexanone, compound 17 is produced in 50% yield. The reaction with aldehydes with zV-chloromethyl-amine yields predominantly acid amides. However, oxaziranes are also produced here as by-products. From benzaldehyde and A -chloro-methylamine, 2-raethyl-3-phenyloxazirane (15) was obtained in 10% yield. 

The reaction starts with the nucleophilic addition of a tertiary amine 4 to the alkene 2 bearing an electron-withdrawing group. The zwitterionic intermediate 5 thus formed, has an activated carbon center a to the carbonyl group, as represented by the resonance structure 5a. The activated a-carbon acts as a nucleophilic center in a reaction with the electrophilic carbonyl carbon of the aldehyde or ketone 1 ... 

Simple 1-hetero-substituted allyllithium derivatives, such as 1-alkoxy-94"96, 1-alkyl-thio-50,97, 1-phenylselenyl-54,98 show insufficient regio- and simple diastereoselectivity in their reaction with aldehydes. The rcgiosclectivity is greatly enhanced in favor of the a-products by in... 

A suspension of 200 mg (0.56 mmol) of 1.4-diben7yl-2,3,6,7-tctrahydro-6,7-dihydroxy-l,4-diazocine-5,8-(l//.4//)-dione in 5 mL of dry CH,CI, is treated with 98 j.iL (0.56 mmol) of tri-2-propenylborane at 23 °C. The suspension becomes a clear solution within a few minutes. The solution is stirred for 3 h before being concentrated in vacuo with exclusion of moisture. The resulting white foam is stripped overnight at 0.1 Torr to give the reagent that is used directly in reactions with aldehydes. 

The method of preparation in the second case is similar, with the exception that catalytic triethylamine is used and the reaction is performed at reflux34. The reagent is isolated by concentration in vacuo, and is also used immediately in reactions with aldehydes. This method is not suited, however, for the synthesis of 2-butenylboron reagents owing to the configurational instability of tri-2-butenylborane which is a rapidly interconverting mixture of E- and Z-isomers2 8. 

These reagents are not isolated but are used directly in reactions with aldehydes, after generation of ate complexes via the addition of an alkyllithium reagent or pyridine11. 2-(2-Propenyl)-1,3,2-dioxaborolane is also metalated upon treatment with lithium tetramethylpiperidide, but mixtures of a- and y-substitution products are obtained upon treatment of this anion with alkylating agents20. Consequently, this route to a-substituted allylboron compounds appears to be rather limited in scope. 

Chiral, nonracemic allylboron reagents 1-7 with stereocenters at Cl of the allyl or 2-butenyl unit have been described. Although these optically active a-substituted allylboron reagents are generally less convenient to synthesize than those with conventional auxiliaries (Section 1.3.3.3.3.1.4.), this disadvantage is compensated for by the fact that their reactions with aldehydes often occur with almost 100% asymmetric induction. Thus, the enantiomeric purity as well as the ease of preparation of these chiral a-substituted allylboron reagents are important variables that determine their utility in enantioselective allylboration reactions with achiral aldehydes, and in double asymmetric reactions with chiral aldehydes (Section 1.3.3.3.3.2.4.). 

Alkoxy-substituted allylaluminum reagents diethyl[(Z)-3-methoxy-2-propenyl]- and -[(Z)-3-(l-methoxy-l-methylethyl)-2-propenyl]aluminum have been prepared by treatment of the corresponding alkoxyallyllithiums with diethylaluminum chloride in tetrahydrofuran at — 78 =C4. These reagents provide the syn-diastereomer with 9-11 1 selectivity in reactions with aldehydes at — 78 °C. The reaction of diethyir(Z)-3-methoxy-2-propenyl]a]uminum and acetophenone provided the iy -diastereomer with 4 1 selectivity. 

The lithium 2-butenyl(triethyl)aluminate complex, prepared in situ from 2-butenyllithium and triethylaluminum, displayed poor diastereoselectivity in a reaction with benzaldehyde (anti/syn 56 44)7. (Z)-3-Alkoxy-substituted aluminate complexes such as A-C, however, give good diastereoselectivity in aldehyde addition reactions8. The reactions of A with aldehydes at —100 °C give the jyw-diol monoether with >95% diastereoselectivity and >80-95% regiose-... 

Chiral amides of 2-(tributylstannylmethyl)-2-propenoic acid show useful stereoselectivity in their Lewis acid induced reactions with aldehydes, and the products have been converted into optically active a-methylenelactones95. 

Aldol reactions of a-substituted iron-acetyl enolates such as 1 generate a stcrcogenic center at the a-carbon, which engenders the possibility of two diastereomeric aldol adducts 2 and 3 on reaction with symmetrical ketones, and the possibility of four diastereomeric aldol adducts 4, 5, 6, and 7 on reaction with aldehydes or unsymmetrical ketones. The following sections describe the asymmetric aldol reactions of chiral enolate species such as 1. 

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