Ketones aldol intramolecular reactions

Another example of a [4S+1C] cycloaddition process is found in the reaction of alkenylcarbene complexes and lithium enolates derived from alkynyl methyl ketones. In Sect. 2.6.4.9 it was described how, in general, lithium enolates react with alkenylcarbene complexes to produce [3C+2S] cycloadducts. However, when the reaction is performed using lithium enolates derived from alkynyl methyl ketones and the temperature is raised to 65 °C, a new formal [4s+lcj cy-clopentenone derivative is formed [79] (Scheme 38). The mechanism proposed for this transformation supposes the formation of the [3C+2S] cycloadducts as depicted in Scheme 32 (see Sect. 2.6.4.9). This intermediate evolves through a retro-aldol-type reaction followed by an intramolecular Michael addition of the allyllithium to the ynone moiety to give the final cyclopentenone derivatives after hydrolysis. The role of the pentacarbonyltungsten fragment seems to be crucial for the outcome of this reaction, as experiments carried out with isolated intermediates in the absence of tungsten complexes do not afford the [4S+1C] cycloadducts (Scheme 38). 

A particularly important example of the intramolecular aldol reaction is the Robinson annulation, a procedure that constructs a new six-membered ring from a ketone.171 The reaction sequence starts with conjugate addition of the enolate to methyl... 

The intramolecular reductive aldol reaction of keto-enones was successfully conducted under conditions similar to those described above, employing a cationic Rh complex and PI13P (Scheme 20) [34]. The keto-enone 63 was cyclized in the presence of added K2CO3 to give the ketone-aldol 64 in 72% yield with exclusive ds-selectivity. Dione-enone derivatives, for example 68 and 70, were efficiently cyclized to furnish bicyclic aldol products 69 and 71, respectively, wherein three stereogenic centers of the bicyclic product form stereoselectivity through the intermediacy of a Rh-enolate. 

Substituted, 2,3-disubstituted, and 2,3-annulated thiophenes can be prepared by reactions of ketone enolates with carbonodithioic acid O-ethyl 5-(2-oxoethyl)ester. Hydrolysis of the resulting aldols, intramolecular addition of thiol group to the carbonyl group, and elimination of two molecules of water lead to the thiophenes (116) (Scheme 38) (92HCA907). 

The starting material for the present synthesis was Wieland-Miescher ketone (24), which was converted to the known alcohol (25) by the published procedure [10], Tetrahydropyranylation of alcohol (25) followed by hydroboration-oxidation afforded the alcohol (26), which on oxidation produced ketone (27). Reduction of (27) with metal hydride gave the alcohol (28) (56%). This in cyclohexane solution on irradiation with lead tetraacetate and iodine produced the cyclic ether that was oxidized to obtain the keto-ether (29). Subjection of the keto-ether (29) to three sequential reactions (formylation, Michael addition with methyl vinyl ketone and intramolecular aldol condensation) provided tricyclic ether (30) whose NMR spectrum showed it to be a mixture of C-10 epimers. The completion of the synthesis of pisiferic acid (1) did not require the separation of epimers and thus the tricyclic ether (30) was used for the next step. The conversion of (30) to tricyclic phenol (31) was... 

Kocienski and coworkers [98] have reported the synthesis of 8-membered cyclic ketones by intramolecular aldol reaction of enol silanes and acetals mediated by Lewis acid. 

An imino group also directs the selective cleavage of orfho-C-H bonds. The reaction of aromatic imines with CO and ethylene in the presence of Ru3(CO)i2 gave the expected ketones. However, the reaction did not stop at the carbonylation step, but an in-situ intramolecular aldol-type reaction proceeded to give indenone derivatives as the final products (Eq. 9.28) [41]. Treatment of the reaction mixture with silica gel selectively afforded indenones in good yields. 

An interesting variation in this reaction combined an intermolecular Mukaiyama aldol followed by an intramolecular reaction (a domino Mukaiyama aldol) that gave cyclic conjugated ketone products.Borane derivatives such as C=C—OB(NMe2)2 react with aldehydes to give p-amino ketones. ... 

Diazo ketones also possess an electrophilic diazo group, and hence are susceptible to diazo-coupling reactions with suitable soft nucleophiles. Examples are given in equations (11) and (12). Phospha-zines such as (19) are useful synthetic intermediates in their own right. The carbon terminus of the 1,3-dipole possesses nucleophilic properties and can participate in aldol-type reactions with the particularly electrophilic carbonyl groups in 1,2-di- and 1,2,3-tri-carbonyl compounds. Intramolecular condensations occur with greater ease (equation 13). Reaction of diazo ketones of the type summarized in equations (9)-(12) have been thoroughly reviewed. ... 

A tandem aldol/intramolecular enol cyclization of epoxyaldehydes to form a-furyl carbinols, 127, has been reported <05TL5467>. Only isopropyl methyl ketones or t-butyl methyl ketones have been shown to work in this reaction. The corresponding A-Boc aziridine aldehyde 127 (X = Af-Boc) has also been used to generate an a-amino furan in excellent yield. 

Strongly solvent-dependent and is unsuccessful in THF, chloroform, benzene, and Other cyclizations utilize the Pd-catalyzed intramolecular aldol reaction of aldehydes with ketone enolates. The reaction is initiated by the oxidative addition of allylic esters to Pd(0) (Scheme 38)/ Chiral ferrocenyl phosphines with polar... 

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 You group examined o-camphor derived NHCs to conduct intramolecular A7-tethered aldehyde-ketone benzoin reactions. With 15 mol% of D-camphor-derived triazolium salt G1 and 10 mol% of NaOAc, various substituted dihydroquinolinone derivatives 10 were obtained with a quaternary carbon stereocentre in moderate to good yields and excellent enantiomeric excesses, a weak base is used to minimise the possible aldol side reaction (Scheme 20.7). 

Nitro groups can be added to organic molecules through an aldol reaction between the anion of a nitroalkane and an aldehyde or ketone carbonyl. Intramolecular aldol reactions can be used to create five- or six-membered rings from dicarbonyl compounds (either aldehydes or ketones), which form in preference to smaller or larger rings that may be possible. 

Recently, Yuan and coworkers reported a similar synthesis [59]. In this report, the spirooxindoles 106 were synthesized by an asymmetric aldol reaction between the 3-isothiocyanatooxindoles 104 and ketones 105. The reaction started with the asymmetric aldol reaction catalyzed by a bifunctional thiourea-tertiary amine catalyst XXVIII, which was followed by intramolecular cyclization between the aldol and isothiocyanate moiety. The reaction tolerated the use of disubstituted aryl alkyl ketones or dialkyl ketones to afford the corresponding cyclospiro products in excellent yields and diastereo and enantioselectivities (Scheme 10.38). 

C)5W=C(0Et)CH=C(0Et)CH=CR(02CR)]. Aldehydes or ketones react with the [diosphine complexes, [(OC)4(PR3)Cr=C(OMe)Me] to give aldol condensation products. Reaction with the amino carbene complexes [(OC)sCr=C(NMe2)Me] results in aldol addition products. Aldol reactions of optically active aminocarbene complexes proceed with moderate to high diastereoselectivity. Photolysis of chromium alkoxycaibene complexes with aldehydes in the presence of Lewis acids produces -lactones in low yield. Intramolecular reaction by incorporation of the aldehyde into either side chain of the carbene complex is considerably more efficient. ... 

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