Aldehydes, addition onto

Michael-like nucleophilic addition onto unsaturated 0 aldehyde y OH... 

In 1977, an article from the authors laboratories [9] reported an TiCV mediated coupling reaction of 1-alkoxy-l-siloxy-cyclopropane with aldehydes (Scheme 1), in which the intermediate formation of a titanium homoenolate (path b) was postulated instead of a then-more-likely Friedel-Crafts-like mechanism (path a). This finding some years later led to the isolation of the first stable metal homoenolate [10] that exhibits considerable nucleophilic reactivity toward (external) electrophiles. Although the metal-carbon bond in this titanium complex is essentially covalent, such titanium species underwent ready nucleophilic addition onto carbonyl compounds to give 4-hydroxy esters in good yield. Since then a number of characterizable metal homoenolates have been prepared from siloxycyclopropanes [11], The repertoire of metal homoenolate reactions now covers most of the standard reaction types ranging from simple... 

Lithiated epoxides are more commonly trapped by electrophiles, generating elaborated oxiranes. In this arena, Hodgson and co-workers <04OL4187> have optimized the lithiation of non-stabilized terminal epoxides with iec-hutylhthium assisted by diamine ligands, such as dibutylbispidine (DBB, 99) or (-)-sparteine 100. The oxiranyl anions thus formed engage in smooth nucleophilic addition onto aldehydes to form epoxyalcohols e.g., 101) the same conditions can be used for the stannylation of epoxides e.g., 84 102). Similarly,... 

Unbranched and substituted alkyl carbamates, such as 146 or 147 [62,88] do not cause any problems in the deprotonation step. Deuteration (with CH3OD or dissolved CH3CO2D), methoxycarbonylation (gaseous CO2, followed by diazomethane after work-up or methyl chloroformate), alkylation with methyl iodide, substitution with trialkylsilyl chlorides, trialkyltin chlorides and even tri-methyllead bromide, addition onto aldehydes and ketones, and acylation with acid chlorides or esters, all proceed without difficulties. Although a ketone is formed in the latter reactions, which is at least 15 orders of magnitude thermodynamically more acidic than the alkyl carbamate we never observed enolate formation, racemization or epimerization - with one exception it occurred to some extent after formylation with formate esters [79]. 

Even though the purity of chiral vinyl sulfoxide was over 99%, the aldol-type vinyl anion addition onto aldehyde to generate the chiral vinyl alcohol was low in e.e. value. The diastereomers could, however, be separated by chromatography and subjected to... 

ThefoUowingdominoreactiondevelopedbyj0rgensenandco-workers [44a] involves enamine activation of aldehydes by diphenylprolinol silyl ether promoting an enantioselective Michael addition onto quinones, followed by an intramolecular hemiacetaliza-tion (Scheme 16.22). The resulting dihydrobenzofiirans were obtained with high yields... 

Addition onto aldehydes or ketones to form cyanohydrin derivatives... 

In an interesting example, two unsaturated aldehydes form each the corresponding enamine in the presence of a proUne-derived catalyst. A first iminium-enamine Michael addition is followed by a second addition onto the unsaturated ester function present in one of the initial reagents. Photoinduced electron transfer and debromination give a radical that adds onto methacrylic aldehyde and cyclize to a highly functionalized decaline 60 (see Scheme 8.27) [46]. 

The enzyme oxinitrilase also catalyzes the addition of prussic acid to 3-phenoxy benzaldehyde 2S0 in a moderate enantioselective manner to give the unsuitable R-enantiomer of299 [640,641]. An artificial enzyme proved to be much more efRcient. The cyclic dipeptide cyclo-(R-Phe-R-His) 300 catalyzes the enantioselective HCN-addition onto aldehydes [642] (Reaction scheme 213). In the case of 3-phenoxy benzaldehyde the desired S-enantiomer 299 is created with a high optical and chemical yield [643-646] optimally in the absence of water in aprotic solvents, catalyzed by some cyanohydrine [647] or aralkyl-alcohol [618]. Rigorous exclusion of traces of basic by-products and a preceding acidic purification step [649] gives additional improvement. 

The present case solves the problem via protective group chemistry [27]. In substrate 53 the vicinal ester function exerts a low Felkin Anh (FA) control onto the aldehyde addition and gives stereoisomer 54 with low diastereoselectivity. The remote O-benzyl protected stereocenter is virtually without effect. This is totally different in the TBDPS-protected substrate 55. In this example, both carbinol centers act together in a matched fashion to produce the FA diastereomer 56 exclusively. The authors interpret this phenomenon with a chromium-complexed carbonyl oxygen that is oriented away from the O-protected center. The bulkier the protecting group is, the more pronounced this orientation and hence the FA-selectivity will be (Scheme 3.13). 

At the start of this work, the dual nucleophilic-electrophilic character of the a-sulfonyl carbanion 213 created some problems since this anion could react not only with the carbonyl derivative (aldehyde or ketone) but also with itself, generating via this competitive pathway some homocoupling by-products. However, a wise selection of the sulfone electrophilic substituent and the use of Barbier-type conditions considerably increased the chemoselectivity of the addition reaction and directed the addition onto the carbonyl function. Benzothiazole derivatives (hereafter denoted BT) were the first substrates to be utilized in this process. After some fine tuning, they proved to be suitable candidates, affording the desired alkenes with a reasonable efficiency (Table 3.11). 

Organomagnesiums frequently prove superior also in other types of reactions. They may facilitate the oxidation of a carbon-metal to a carbon-oxygen bond, secure clean monoaddition of an acetylide to an activated ester (a critical issue in a monensin synthesis X favor in the presence of a copper catalyst 1,4-addition onto a conjugated enone over 1,2-addition, reorient the attack of formaldehyde on a benzylic entitiy from the a- to the or /to-position, and provide diastereoselectivity in nucleophilic additions onto aldehydes. Furthermore organomagnesiums combine under carbon-carbon linking with a variety of organic halides, tosylates, and acetates if the process is mediated by transition elements such as palladium(O) copper(I), nickel(II) or iron(II) Organoalkalis are often less fit to enter such catalytic cycles. 

Scheme 1-154. Organolithium addition onto 5-(trimethylsilyl)oxy-2,4-pentadienal and subsequent hydrolysis to the a,P y,8-unsaturated aldehyde 211.

Tin transfer onto aldehydes occurs under NHC catalysis. While NHC (162) promotes the 1,2-addition of Bu3Sn-SiMe3 onto aliphatic aldehydes, it also promotes 1,4-addition onto / -substituted enals, thereby furnishing y-silyloxyallylstannanes (163). The 1,4-addition has been further coupled to a Lewis-acid-mediated allylstannation reaction, allowing the diastereoselective preparation of iyn-diols (164) in a one-pot manner (Scheme 11). 

The nucleophilic addition onto aldehydes was also extended to alkynyltributyltins, which were found to be reactive upon transmetallation with catalytic amount of InClj [247]. The direct addition of alkynyltrimethyltins onto j8-alkoxy aldehydes... 

The hydration of triple bonds is generally carried out with mercuric ion salts (often the sulfate or acetate) as catalysts. Mercuric oxide in the presence of an acid is also a common reagent. Since the addition follows Markovnikov s rule, only acetylene gives an aldehyde. All other triple-bond compounds give ketones (for a method of reversing the orientation for terminal alkynes, see 15-16). With allqmes of the form RC=CH methyl ketones are formed almost exclusively, but with RC=CR both possible products are usually obtained. The reaction can be conveniently carried out with a catalyst prepared by impregnating mercuric oxide onto Nafion-H (a superacidic perfluorinated resinsulfonic acid). ... 

Hydrogenolysis of esters to aldehydes or alcohols needs high temperatures and high pressures. Moreover, it leads to the formation of acids, alcohols, and hydrocarbons. In contrast, bimetallic M-Sn alloys (M = Rh, Ru, Ni) supported on sihca are very selective for the hydrogenolysis of ethyl acetate into ethanol [181]. For example while the selectivity to ethanol is 12% with Ru/Si02, it increases up to 90% for a Ru-Sn/Si02 catalyst with a Sn/Ru ratio of 2.5 [182]. In addition, the reaction proceeds at lower temperatures than with the classical catalysts (550 K instead of temperatures higher than 700 K). The first step is the coordination of the ester to the alloy (Scheme 46), and most probably onto the tin atoms. After insertion into the M - H bond, the acetal intermediate decomposes into acetaldehyde and an ethoxide intermediate, which are both transformed into ethanol under H2. 

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