Transition intramolecular additions

Phenylthio)nitroalkenes are also excellent intermediates for the synthesis of other heterocyclic ring systems. For example, tetrahydropyran carboxylic acid derivatives are formed by the intramolecular addition of oxygen nucleophile to l-(phenylthio)nitroalkene predominantly as the m-isomer (9.1 1) (see Eq. 4.40). The reaction may proceed via the chair-like transition state with two pseudo-equatorial substituents.50... 

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]. 

Organic Electroreductive Coupling Reactions using Transition Metal Complexes as Catalysts Table 11. Co- or Ni-catalyzed intramolecular additions to Michael acceptors... 

The mixture of quinone methides initially formed by combination of the coniferyl radicals in their various mcsomeric forms, i.e. (I), (III), (V), (IX) and others, can be detected by means of their characteristic spectrum with a maximum at about 312 mp (52) the haU-hfe of the mixture in 70 % aqueous dioxan is 1 hour. Those quinone methides that can rearomatize by keto-enol tautomerism, e.g. (IX), or intramolecular additions, e.g. (I) or (III) may become stabilized faster than those of type (V) which rely on addition of a foreign molecule. The quinone methides that rearomatize intramolecularly appear to react exclusively in this way, probably by a concerted mechanism that represents collapse of the activated transition state. 

Terminal alkynes readily react with coordinatively unsaturated transition metal complexes to yield vinylidene complexes. If the vinylidene complex is sufficiently electrophilic, nucleophiles such as amides, alcohols or water can add to the a-carbon atom to yield heteroatom-substituted carbene complexes (Figure 2.10) [129 -135]. If the nucleophile is bound to the alkyne, intramolecular addition to the intermediate vinylidene will lead to the formation of heterocyclic carbene complexes [136-141]. Vinylidene complexes can further undergo [2 -i- 2] cycloadditions with imines, forming azetidin-2-ylidene complexes [142,143]. Cycloaddition to azines leads to the formation of pyrazolidin-3-ylidene complexes [143] (Table 2.7). 

Intramolecular additions generally follow the same trends of stereoselectivity as observed in the bimolecular reactions. Eor example, allylic boronates ( )- and (Z)-118 provide the respective trans- and cis-fused products of intramolecular aUylation. As shown with allylboronate ( )-118, a Yb(OTf)3-catalyzed hydrolysis of the acetal triggers the intramolecular aUylboration and leads to isolation of the trans-fused product 119 in agreement with the usual cyclic transition structure (Eq. 96). 

Cyclization to a morpholinolactone (59) occurs in the hydrolysis reaction of the di-A-hydroxylethylated compound (60). Compound (59) is rapidly hydrolysed by water to (61) but in file presence of equimolar amounts of amines (RNH2) or ammo acid derivatives (62) forms.56 A novel reaction of cyclic 2-diazo-l,3-dicarbonyl compounds (63) with lactones (64) affords the products (65) in the presence of rhodium acetate, Rh2(OAc)4.57 Lewis acid-promoted intramolecular additions of allylsilanes to lilac tones gave substituted cyclopentanes.58 A proposed transition state guided efforts to improve the stereoselectivity of the reaction. The reaction of a series of /1-lactone derivatives, such as (66)-(68), has been studied and they have been ling cleaved the reaction outcome is both Lewis acid and structure dependent.59... 

Transition metal compounds having a phosphoranide ligand remained unknown. The approach we chose to accede to this new class of compounds was to provoke the intramolecular addition of an ionic fifth substituent on the phosphorus atom of a phosphane previously coordinated to the transition metal. The anionic site was created by abstraction of a proton from a secondary amine. 

The transition metal-catalyzed addition of alcohols to unsaturated systems has not been widely investigated. Reports on addition of alcohols to 1,3-diene [24] or allene [25] have appeared but have very limited scope. We recently reported the palladium/benzoic acid-catalyzed inter- and intramolecular addition of alcohols to alkynes in which various acyclic and cyclic allylic ethers are produced [26], The Pd-catalyzed addition of alcohols to alkylidenecyclopropanes proceeds smoothly providing a powerful tool for synthesis of allylic ethers [27a]. An intramolecular version of the hydroalkoxylation has been demonstrated in which the phenol-tethered alkylidenecyclopropanes undergo facile cyclization to give exomethylene products [27b],... 

Intramolecular addition of amine N-H bonds to carbon-carbon multiple bonds would afford nitrogen heterocycles. To realize catalytic cyclization of a,co-aminoalkenes or aminoalkynes, various catalytic systems have been developed especially with early transition metals such as titanium, zirconium, lanthanide metals, and actinide metals [ 12], Late-transition-metal catalysis based on Ni, Pd, and Rh has also proved to be efficient [ 12], Recently, the ruthenium-catalyzed intramolecular hydroamination of aminoalkynes 15 was reported to afford 5-7-membered ring products 16 in various yields (Eq. 6) [13]. Among... 

The analogous reaction using tetramethyltitanium 14 results in a 42 58 product ratio, whereas CH3MgI is non-selective (1 1 mixture) 83). It is possible that in case of 14 the transfer of the second methyl group occurs to some extent intramolecularly via a bicyclo[l,l,4] transition state. Indeed, sixfold dilution (which should reduce the amount of intermolecularity) reverses diastereoseleetivity, 166 167 being 52 48 83). Clearly, systematic studies are required before final conclusions regarding the use of titanium or zirconium mediated intramolecular addition reactions can be reached. 

The observed regioselectivities and stereoselectivities of the intramolecular addition of a carbon-lithium bond to an unactivated alkene (Table 1) could be rationalized by recourse to a transition-state model that resembles a cyclohexane chair in which substituents preferentially occupy pseudo-equatorial positions (structures 26-28). The same model is proposed to explain the modest selectivities in the analogous radical cyclizations (Scheme 8). 

More remote stereoselcction is achieved in the hydroboration of 1,4- and 1,5-dienes with thexylborane. The first stereogenic center is created by intermolecular hydroboration of the terminal double bond. This then directs the intramolecular addition to the second double bond proceeding via a cyclic transition state and leading to high levels of selectivity46. 

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]. 

Figure 17. Transition-state possibilities for intramolecular additions of (Z)- and ( )-allylic stannanes.

Experimental and theoretical studies on the isomerization of allyl thiocyanate to aUyl isothiocyanate have indicated that the transformation proceeds by a [3,3]-sigmatropic rearrangement involving a cychc transition state. A novel tandem [3,3]-sigmatropic rearrangement of allylic thiocyanates (129) followed by a stereo-controlled intramolecular addition of the amino function to the developing isothiocyanate group, has... 

Exan les of intramolecular addition reactions of alkenylchromium reagents to aldehydes have ap-peared. In the course of synthetic studies in the brefeidin structural series, the nickel(II)/chro-miiun(II)-mediated intramolecular addition reactions of ( )-iodoalkenes (227) and (230) were studied by Schreiber and Meyers (equations 72 and 73). Treatment of (227) with CrCh and a catalytic portion of [Ni(acac)2] in DMF produced a 4 1 mixture of 4-epibrefeldin C (228) and (+)-brefeldin (229) in 60% yield. In a similar fashion, precursor iodide (230) afforded a >10 1 mixture of cyclized hydroxy lactones (231) and (232) in 70% yield. An explanation of the stereochemical preference observ has been elo-quendy offered in a discussion of loc conformational preferences found in the starting material and the product lactone, as each is relevant to a transition structure for a 13-membered ring closure. 

There continues to be a high level of interest shown in photochromic systems. The optically active l,T-bi-2-naphthol gives an optically active intramolecular addition product (37) on irradiation, and on prolonged exposure, cycloreversion occurs which gives evidence for a photoequilibrium between the asymmetric molecules (Cavazza et al). A number of reports within the year describe a variety of aspects of the well-known thermally-reversible spiroindoline-oxazine to photo-merocyanine conversion. For example, the process is sensitised by triplet cam-phorquinone (Favaro et al.), the influence of complexation on indoline and phenanthroline spiropyrans with transition and rare earth metal ions has been described (Atabekyan et al.), and the photochromism of other derivatives in water using vesicles and y-cyclodextrin is reported to be faster than in methanol with the process most favoured in the vesicles (Ishiwatari et al.). 

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