Aldol-like intramolecular

The following reaction involves an intramolecular aldol reaction followed by a retro aldol-like reaction. Write both steps, and show their mechanisms. 

Epoxide rings may also be opened by intramolecular nucleophiles derived from allylsilane groups (see Scheme 9) to permit aldol-like closure onto aldehyde functions. Compound 63 (Scheme 15), derived by a multistep route from L-arabinose, when activated... 

Another common trapping method is an intramolecular aldol reaction of the initially formed anion, as shown in equation (91) and Schemes 53 and 54.% In the first case, an aldol-like trapping of the iminium salt produced (411 equation 91 ).96b The initial heteronucleophile in the other two cases is ultimately lost from the product by oxidation and elimination, so that the overall process is C—C bond formation at the a-center of an enone. Thus, treatment of the formyl enone (412 Scheme 53) with an aluminum thiolate afforded in 60% yield the trapped product (413) which could be oxidized and eliminated to give (414).96c Addition of the corresponding aluminate species to the ketoacrylate (415 Scheme 54) produced only one diastereomer of the aldol product (416) which was converted into the alkene (417) in excellent yield.96 1... 

Heteroarylamines, for example 1195, react with (dimethylamino)propenoate 1196 to yield an imidazolecarboxylate 1199. The imidazole ring is formed via the intermediate diaminoalkenoate 1197, which undergoes an intramolecular Michael addition followed by a retro-aldol-like reaction (Scheme 294) <1998JHC1527>. Similarly, 4-dimethyl-amino-2-aza-l,3-dienes 1200, serving as y-dielectrophiles, condense with amines or hydrazines neat at 70 °C to form A -substituted imidazole-4-carboxylates 1201 in 60-75% yields (Scheme 294) <1999TL8097>. 

The CeY zeolite is utilized for the preparation of 4-methylcoumarin by the reaction of phenol with AAN. The formation of PA represents the first step the subsequent acylation at the ortho position, followed by an intramolecular aldol-like condensation, affords the final 4-methylcoumarin in 75% yield (Scheme 5.8). In the entire process, the cerium-catalyst shows a bifunctional character the active centers in the supercage of CeY zeolite, the Ce + ions, act as Lewis acid catalysts, whereas the acid centers H+, formed by the dissociation of water according to the equation Ce + + H2O [Ce(OH)]2+ + H+, act as Bronsted catalysts. 

In another advance outlined in Scheme 9.41, the Madelung synthesis was modernized by employing an intramolecular Wittig reaction (Chapter 4, section 4.3) instead of the aldol-like condensation of Scheme 9.39. ... 

Highly substituted 3-pyrrolin-2-ones, especially congeners-containing substitution at C-3 and/or C-4, are often prepared utilizing intramolecular aldol-like condensations of a-amidoketones 122 (Scheme 21). Jacobi and coworkers prepared a 3,4-dialkyl-3-pyrrolin-2-one (Scheme 21 R, = CH2CH2SeAr = Me) by treating an a-amidoketone 122 with i-BuOK this was a key step in a synthesis of the pyrromethenone moiety... 

Mechanistically, the reaction of diketosulfides and glyoxal likely proceeds via an initial aldol reaction to provide 22. A second intramolecular aldol reaction and the elimination of two equivalents of water produce the thiophene 23. The timing of the elimination reactions and the ring-closing, carbonyl condensation reaction is not completely understood. However, 2,5-disubstituted thiophenes 23 are available in good yields via this process. 

Mikami has carried out a number of investigations aimed at elucidating mechanistic aspects of this Si-atom transfer process. In particular, when the aldol addition reaction was conducted with a 1 1 mixture of enoxysilanes 60 and 62, differentiated by the nature of the 0-alkyl and 0-silyl moieties, only the adducts of intramolecular silyl-group transfer 63 and 64 are obtained (Scheme 8B2.6). This observation in addition to results obtained with substituted enol silanes have led Mikami to postulate a silatropic ene-like mechanism involving a cyclic, closed transition-state structure organized around the silyl group (Scheme 8B2.6). 

Tropoelastin molecules are crosslinked in the extracellular space through the action of the copper-dependent amine oxidase, lysyl oxidase. Specific members of the lysyl oxidase-like family of enzymes are implicated in this process (Liu etal, 2004 Noblesse etal, 2004), although their direct roles are yet to be demonstrated enzymatically. Lysyl oxidase catalyzes the oxidative deamination of e-amino groups on lysine residues (Kagan and Sullivan, 1982) within tropoelastin to form the o-aminoadipic-6-semialdehyde, allysine (Kagan and Cai, 1995). The oxidation of lysine residues by lysyl oxidase is the only known posttranslational modification of tropoelastin. Allysine is the reactive precursor to a variety of inter- and intramolecular crosslinks found in elastin. These crosslinks are formed by nonenzymatic, spontaneous condensation of allysine with another allysine or unmodified lysyl residues. Crosslinking is essential for the structural integrity and function of elastin. Various crosslink types include the bifunctional crosslinks allysine-aldol and lysinonorleucine, the trifunctional crosslink merodes-mosine, and the tetrafunctional crosslinks desmosine and isodesmosine (Umeda etal, 2001). 

The Robinson annulation is a ring-forming reaction that combines a Michael reaction with an intramolecular aldol reaction. Like the other reactions in Chapter 24, it involves enolates and it forms carbon-carbon bonds. The two starting materials for a Robinson annulation are an a,P-unsaturated carbonyl compound and an enolate. 

Jht last conjugate addition in the synthesis of the first compound is fairly obvious as the jBET.bination of ester and ketone provides a good enolate. Then we have a cyclohexenone rather like at compound in Problem 6. The compound needed for the intramolecular aldol reaction can be faiace by a second conjugate addition using a stable enolate. 

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