Intramolecular aldehydes

Hachisu Y, Bode JW, Suzuki K (2003) Catalytic intramolecular crossed aldehyde-ketone benzoin reactions a novel synthesis of functionalized prean-thraquinones. J Am Chem Soc 125 8432-8433 Hachisu Y, Bode JW, Suzuki K (2004) Thiazolium ylide-catalyzed intramolecular aldehyde-ketone benzoin-forming reactions substrate scope. Adv Synth Catal 346 1097-1100... 

The products of the asymmetric alkylation have been used as key building blocks in syntheses of morphanes, phyllanthocin, and periplanone B natural products. In the case of the synthesis of the morphane skeleton, a phenolic nucleophile was reacted with cyclohexenyl methyl carbonate and the resulting ether was subjected to a europium-induced Claisen rearrangement followed by an intramolecular aldehyde-ene reaction to generate the key tricyclic intermediate. Scheme 27 [56]. 

However, the reaction of diazonium chlorides with N,N-dimethyl-formamide proceeds in a different manner, giving rise to an intramolecular aldehyde formation. For example, from benzenediazonium chloride and N,N-dimethylformamide, salicylaldehyde CLXXIX was obtained in low yield ( ° ). 

Using the camphor-derived triazolium salts initially developed by their own group. You and co-workers developed an enantioselective NHC-catalyzed intramolecular aldehyde-ketone benzoin reaction with N-tethered substrates. Various substituted dihydroquinolinone derivatives were obtained with a quaternary carbon stereogenic center in moderate to good yields and excellent ee (up to 96% yield, 92% ee). The utilization of a weak base (NaOAc) is critical for minimizing the aldol side reaction (Scheme 7.5). 

The intramolecular aldehyde-ketone benzoin reaction catalysed by pre-NHC FI was reported by Suzuki et al. It was found that the size of the substituent at the ketone moiety could influence the enantiomeric excess (Scheme 20.5). Recently, Sakai and Ema reported the intramolecular crossed benzoin reactions of cyclic diketones (Scheme 20.6). " In the presence of 30 mol% of... 

Suzuki and co-workers [23] extended the scope of the intramolecular aldehyde-ketone benzoin reaction for the synthesis of natural products with a-keto tertiary alcohols in up to 99% ee. It was found that the size of the substituent at the ketone moiety could influence the enantiomeric excess. For example, 39% ee resulted for the methyl ketone, while 90% ee resulted for the ethyl ketone (Scheme 7.8). To extend the scope of the reaction, they modified the Rovis triazolium salts by introducing electron-withdrawing substituent(s). Under the catalyst of triazolium salt 12, the a-keto tertiary alcohol 14 resulted in 92% yield and 95% ee, which was then transformed into (+)-sappanone B (Scheme 7.9) [24]. An asymmetric desym-metrization strategy was utilized by Saka and Ema for the intramolecular crossed... 

A review of the asymmetric Stetter and asymmetric benzoin reactions focuses mainly on two classes of highly successful catalysts NHCs and metallophosphites. A new NHC, pyrido[l,2-a]-2-ethyl[l,2,4]triazol-3-ylidene (99), is a powerful catalyst of benzoin condensation in the presence of potassium f-butoxide. A DFT study of the mechanism suggests that the f-butanol solvent is explicitly involved. o-Phthalaldehyde chalcones (100) undergo intramolecular aldehyde-ketone crossed-benzoin condensation to naphthalenone tertiary alcohols (101) in yields up to 94%, in 20 min, using NHC catalysis. ... 

For intramolecular aldehyde/allylsilane reactions (1- 2, M = SiR3) see Yamamoto, Y. Sasaki, N. The Stereochemistry of the Sakurai Reaction in Chemical Bonds - Better Ways to Make Them I. Bernal, Ed. Elsevier Science Publ., 1989 pp 363-442. 

Comito, R. J., Finelli, F. G., MacMillan, D. W. C. (2013). Enantioselective intramolecular aldehyde a-alkylation with simple olefins direct access to homo-ene products. Journal of American Chemical Society, 135, 9538-9361. 

An important general method of preparing indoles, known as the Fischer Indole synthesis, consists in heating the phenylhydrazone of an aldehyde, ketone or keto-acld in the presence of a catalyst such as zinc chloride, hydrochloric acid or glacial acetic acid. Thus acrtophenone phenylhydrazone (I) gives 2-phenyllndole (I V). The synthesis involves an intramolecular condensation with the elimination of ammonia. The following is a plausible mechanism of the reaction ... 

The reductive coupling of aldehydes or ketones with 01, -unsaturated carboxylic esters by > 2 mol samarium(II) iodide (J.A. Soderquist, 1991) provides a convenient route to y-lactones (K. Otsubo, 1986). Intramolecular coupling of this type may produce trans-2-hy-droxycycloalkaneacetic esters with high stereoselectivity, if the educt is an ( )-isomer (E.J. Enholm, 1989 A, B). 

Asymmetric cyclization using chiral ligands has been studied. After early attempts[142-144], satisfactory optical yields have been obtained. The hexahy-dropyrrolo[2,3-6]indole 176 has been constructed by the intramolecular Heck reaction and hydroaryiation[145]. The asymmetric cyclization of the enamide 174 using (S j-BINAP affords predominantly (98 2) the ( )-enoxysilane stereoisomer of the oxindole product, hydrolysis of which provides the ( l-oxindole aldehyde 175 in 84% yield and 95% ec. and total synthesis of (-)-physostig-mine (176) has been achieved[146]. 

Enamines derived from ketones are allylated[79]. The intramolecular asymmetric allylation (chirality transfer) of cyclohexanone via its 5-proline ally ester enamine 120 proceeds to give o-allylcyclohexanone (121) with 98% ee[80,8l]. Low ee was observed in intermolecular allylation. Similarly, the asymmetric allylation of imines and hydrazones of aldehydes and ketones has been carried out[82]. 

The decarboxylation of allyl /3-keto carboxylates generates 7r-allylpalladium enolates. Aldol condensation and Michael addition are typical reactions for metal enolates. Actually Pd enolates undergo intramolecular aldol condensation and Michael addition. When an aldehyde group is present in the allyl fi-keto ester 738, intramolecular aldol condensation takes place yielding the cyclic aldol 739 as a main product[463]. At the same time, the diketone 740 is formed as a minor product by /3-eIimination. This is Pd-catalyzed aldol condensation under neutral conditions. The reaction proceeds even in the presence of water, showing that the Pd enolate is not decomposed with water. The spiro-aldol 742 is obtained from 741. Allyl acetates with other EWGs such as allyl malonate, cyanoacetate 743, and sulfonylacetate undergo similar aldol-type cycliza-tions[464]. 

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. 

Give the structure of the product denved by intramolecular aldol condensation of the keto aldehyde shown... 

The location of the hydroxyl and aldehyde groups ortho to one another in saUcylaldehyde permits intramolecular hydrogen bonding, and this results in the lower melting point and boiling point and the higher acid dissociation constant observed relative to -hydroxybenzaldehyde. 

Simple olefins do not usually add well to ketenes except to ketoketenes and halogenated ketenes. Mild Lewis acids as well as bases often increase the rate of the cyclo addition. The cycloaddition of ketenes to acetylenes yields cyclobutenones. The cycloaddition of ketenes to aldehydes and ketones yields oxetanones. The reaction can also be base-cataly2ed if the reactant contains electron-poor carbonyl bonds. Optically active bases lead to chiral lactones (41—43). The dimerization of the ketene itself is the main competing reaction. This process precludes the parent compound ketene from many [2 + 2] cyclo additions. Intramolecular cycloaddition reactions of ketenes are known and have been reviewed (7). 

The most recent, and probably most elegant, process for the asymmetric synthesis of (+)-estrone appHes a tandem Claisen rearrangement and intramolecular ene-reaction (Eig. 23). StereochemicaHy pure (185) is synthesized from (2R)-l,2-0-isopropyhdene-3-butanone in an overall yield of 86% in four chemical steps. Heating a toluene solution of (185), enol ether (187), and 2,6-dimethylphenol to 180°C in a sealed tube for 60 h produces (190) in 76% yield after purification. Ozonolysis of (190) followed by base-catalyzed epimerization of the C8a-hydrogen to a C8P-hydrogen (again similar to conversion of (175) to (176)) produces (184) in 46% yield from (190). Aldehyde (184) was converted to 9,11-dehydroestrone methyl ether (177) as discussed above. The overall yield of 9,11-dehydroestrone methyl ether (177) was 17% in five steps from 6-methoxy-l-tetralone (186) and (185) (201). 

Original Synthesis. The first attempted synthesis of i7-biotin in 1945 afforded racemic biotin (Fig. I). In this synthetic pathway, L-cysteine [52-90-4] (2) was converted to the methyl ester [5472-74-2] (3). An intramolecular Dieckmaim condensation, during which stereochemical integrity was lost, was followed by decarboxylation to afford the thiophanone [57752-72-4] (4). Aldol condensation of the thiophanone with the aldehyde ester [6026-86-4]... 

Ester, aldehyde, carbonate, phosphate, nitrate, nitrite, nitrile, intramolecular bonding, e.g., o-nitrophenol - 0 -1- - -1- -1- 0 -1- -1- 0 -1- -1-... 

Tl mediated Inter or intramolecular addition of allytic silanes to ouMnsaiurated ketones or to aldehydes. 

This sulfonate is prepared by reaction with the sulfonyl chloride. Cleavage occurs with 0.05 MNaOH (acetone, H2O, 25°, 5 min, 83-93% yield). Here also cleavage is facilitated by intramolecular participation through the hydrate of the aldehyde. ... 

With cyclic ketones, the a-cleavage can also be followed by intramolecular bydn en abstraction that leads eventually to an unsaturated ring-opened aldehyde ... 

The most efficient intramolecular secondary processes competing with the acyl-alkyl diradical recombination in five-membered and larger cyclic ketones are hydrogen shifts resulting in the disproportionation of the diradical to either ketenes or unsaturated aldehydes [cf. (5) (4) (6)]. 

---