Aldehydes intramolecular additions

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

Other nucleophiles add to conjugated systems to give Michael-type products. Aniline derivatives add to conjugated aldehydes in the presence of a catalytic amount of DBU (p. 488). Amines add to conjugated esters in the presence of InCla, La(OTf)3, or YTb(OTf)3 at 3kbar, for example, to give P-amino esters. This reaction can be initiated photochemically. An intramolecular addition of an amine unit to a conjugated ketone in the presence of a palladium catalyst, or... 

Depending on the nature of the substrates, selectivity could be completely reversed between the two isomeric products. For example, switching R1 group between Buc and Ph gave high yields of the first and second product structures, respectively. The authors noted that the reaction did not proceed if the imine contained an ortho-MeO group at R2 or if the imine was replaced with an aldehyde, oxime, or hydrazone. The catalytic cycle is initiated by C-H activation of the imine, that is, the formation of a five-membered metallocycle alkyne insertion affords the intermediate drawn in Scheme 69. It is noteworthy that this is the first report of catalytic synthesis of indene derivatives via a C-H insertion mechanism (C-H activation, insertion, intramolecular addition). 

Perhaps the most elusive variant of the aldol reaction involves the addition of metallo-aldehyde enolates to ketones. A single stoichiometric variant of this transformation is known [29]. As aldolization is driven by chelation, intramolecular addition to afford a robust transition metal aldolate should bias the enolate-aldolate equilibria toward the latter [30, 31]. Indeed, upon exposure to basic hydrogenation conditions, keto-enal substrates provide the corresponding cycloal-dol products, though competitive 1,4-reduction is observed (Scheme 22.7) [24 d]. 

Another interesting example of a photochemi-cally induced domino process is the combination of the photocyclization of aryl vinyl sulfides with an intramolecular addition as described by Dittami et al. [901 as intermediate a thiocarbonyl ylide can be assumed. The domino-Norrish I-Knoevenagel-allyl-silane cyclization developed by us allows the efficient stereoselective formation of 1,2-trans-subsituted five- and six-membered carbocycles.1911 A photochemical cycloaddition of enamino-aldehydes and enamino-ketones with the intermediate formation of an iminium salt followed by addition to allylsilanes gives access to novel bicyclic heterocy-des. New examples of photochemically induced... 

Intramolecular addition of trialkylboranes to imines and related compounds have been reported and the main results are part of review articles [94, 95]. Addition of ethyl radicals generated from Et3B to aldimines affords the desired addition product in fair to good yield but low diaster control (Scheme 40, Eq. 40a) [96]. Similar reactions with aldoxime ethers [97], aldehyde hydrazones [97], and N-sulfonylaldimines [98] are reported. Radical addition to ketimines has been recently reported (Eq. 40b) [99]. Addition of triethylborane to 2H-azirine-3-carboxylate derivatives is reported [100]. Very recently, Somfai has extended this reaction to the addition of different alkyl radicals generated from trialkylboranes to a chiral ester of 2ff-azirine-3-carboxylate under Lewis acid activation with CuCl (Eq. 40c) [101]. 

Allenylsilanes undergo intramolecular additions to appropriately positioned aldehydes, imines, conjugated esters and alkenes to afford various alkynylcyclopentane and cyclohexane derivatives (Eqs. 9.66-9.70) [66]. The reactions are promoted by SnCl4 or by thermolysis. The stereochemistry of these cyclization reactions is consistent with a concerted sigmatropic process as illustrated in Scheme 9.17. 

Oxygenated allenylstannanes have also been employed in intramolecular additions to aldehydes [82]. Both six- and seven-membered cyclic ethers have been synthesized with high diastereoselectivity by this route (Eq. 9.103). 

Reduction of unsaturated aromatic aldehydes to unsaturated hydrocarbons poses a serious problem, especially if the double bond is conjugated with the benzene ring or the carbonyl or both. In Clemmensen reduction the a,)8-unsaturated double bond is usually reduced [160], and in Wolff-Kizhner reduction a cyclopropane derivative may be formed as a result of decomposition of pyrazolines formed by intramolecular addition of the intermediate hydrazones across the double bonds [280]. The only way of converting unsaturated aromatic aldehydes to unsaturated hydrocarbons is the reaction of... 

D-Ribofuranose-type phospha sugars 50 (R=OH, Et, and Ph) and 2-deoxy-D-ribofuranose analogues 51 (R=OH and Me) in Fig. 3 have been prepared via longer reaction pathways by a similar ring closing intramolecular addition reaction of a P - H group to an aldehyde of sugars shown in Scheme 14 [17-20]. 

Similar to intermolecular reactions, the intramolecular addition of aldehydes to enones could be also promoted with catalyst 56a (Scheme 2.53) [43]. The cycliza-... 

A perusal of the literature discloses that ketones and aldehydes have rarely been reacted with 44. In view of the tendency of ynamines to add water and alkohols, it is obvious that ynamines 56 undergo intramolecular addition of water (Meyer-Schuster rearrangement) quite readily (96). This process is provoked already by silicagel, alumina or it even occurs spontaneously 146). 

An intermolecular iron-catalyzed ring expansion reaction involving epoxides and alkenes provided tetrahydrofurans via radical processes <07CEJ4312>. Cp2TiCl is able to promote cyclization of 2,3-epoxy alcohols containing a p-(alkoxy)acrylate moiety to form tetrahydrofurans <07TL6389>. As shown in the following example, an intramolecular addition of carbon radicals to aldehydes was reported to afford tetrahydrofuran-3-ols... 

It is suggested that these findings are best accommodated by a synclinal arrangement in the transition state which is favored by HOMO-LUMO orbital interactions, as previously suggested for certain intramolecular additions (Fig. 5). It should be noted that antiperiplanar or the alternative synclinal orientation for these transition states would result in unfavorable steric interactions between the aldehyde substituent, R, and the vinyl Me or (especially) R. ... 

The first Lewis acid-promoted intramolecular addition reaction was conducted as part of a study designed to ascertain the transition-state geometry of allylic stannane additions to aldehydes (Table 45) [77]. 

Allenylstannanes undergo remarkably efficient BFa-promoted intramolecular additions to aldehydes (Eq. 77) [90]. In this way 12-, 14-, and 15-membered rings have been prepared in high yield. The cyclic homopropargylic alcohol products can be converted into 2,5-bridged furan analogs of furanocembranes and pseudopteranes, as illustrated in Eq. (78). 

These cyclizations both involve the reductive intramolecular addition of an electron deficient alkene function to an aldehyde carbonyl function, and both are effected in ca 90 % yields. The mechanism of this latter type of electrochemically induced cyclizations of carbon-carbon double bonds to carbonyl double bonds have been studied rather extensively, with especial attention to the fundamental mechanistic question of whether the cyclization step involves an anion radical, radical, or anionic mechanism [122]. The latter two mechanisms would involve the protonation of the initially formed anion radical intermediate to form a radical, which could then cyclize or, alternatively, be further reduced to an anion, which could then cyclize. Extensive and elegant electrochemical and chemical studies have led to the formulation of these reactions as involving anionic cyclization (Scheme 74). 

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