Intramolecular, addition catalyzed

Because of steric effects epimerization can intervene in an intramolecular addition catalyzed by DBU. ... 

The intramolecular addition of the O-H bond to alkynes catalyzed by palladium complexes has been developed by K. Utimoto et al. (Eq. 6.59) [104]. An alkynyl alcohol can be converted to a cyclic alkenyl ether in the presence of a catalytic amount of [PdCl2(PhCN)2 or [PdCl2(MeCN)2] in ether or THE at room temperature. When the reaction was carried out in MeCN-H20 under reflux in the presence of a catalytic amount of PdCl2, hydration of the acetylenic alcohol occurred and the ketoalcohol was obtained in good yield instead. 

Trost and coworkers [131] synthesized oxaheterocycles by a Pd-catalyzed addition of terminal alkynes onto hydroxyalkynoates, followed by an intramolecular addition of the hydroxyl functionality on the triple bond. Simple lactonization may take place as a side reaction. 

The intramolecular addition of alkynyl-substituted a-diazoketones is catalyzed by Rh2(OAc)4 to give transient cyclopropenes, which spontaneously rearrange to vinylogous a-keto carbene intermediates for further carbon-skeleton transformations [54]. 

Cycloheptane annelation.1 A new route to cycloheptanes is based on a Lewis acid-catalyzed, intramolecular addition of an allylsilane group to a 3-vinylcycloal-kenone (equation I). This annelation has been applied to a synthesis of the ses-... 

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

Figure 4 The biosynthesis of nisin A as a representative example of the posttranslational maturation process of lantibiotics. Following ribosomal synthesis, NisB dehydrates serine and threonine residues in the structural region of the prepeptide NisA. NisC subsequently catalyzes intramolecular addition of cysteine residues onto the dehydro amino acids in a stereo- and regioselective manner. Subsequent transport of the final product across the cell membrane by NisT and proteolytic cleavage of the leader sequence by NisP produces the mature lantibiotic. For the sequence of the leader peptide, see Figure 6. Adapted with permission from J. M. Willey W. A. van der Donk, Annu. Rev. Microbiol. 2007, 61, 477-501.

Intramolecular rhodium-catalyzed carbamate C-H insertion has broad utility for substrates fashioned from most 1° and 3° alcohols. As is typically observed, 3° and benzylic C-H bonds are favored over other C-H centers for amination of this type. Stereospecific oxidation of optically pure 3° units greatly facilitates the preparation of enantiomeric tetrasubstituted carbinolamines, and should find future applications in synthesis vide infra). Importantly, use of PhI(OAc)2 as a terminal oxidant for this process has enabled reactions with a class of starting materials (that is, 1° carbamates) for which iminoiodi-nane synthesis has not proven possible. Thus, by obviating the need for such reagents, substrate scope for this process and related aziridination reactions is significantly expanded vide infra). Looking forward, the versatility of this method for C-N bond formation will be advanced further with the advent of chiral catalysts for diastero- and enantio-controlled C-H insertion. In addition, new catalysts may increase the range of 2° alkanol-based carbamates that perform as viable substrates for this process. 

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). 

The a-enynyl complex Ru(Tp)[PhC=C(Ph)C=CPh](PMe Pr2) 10 efEciently catalyzed the regioselective cyclization of a,(D-alkynoic acids involving an anti-Markovnikov intramolecular addition to give unsaturated lactones [29] (Equation 10.5). 

The intramolecular addition of carbon nucleophiles to alkenes has received comparatively little attention relative to heterocyclization reactions. The first examples of Pd-catalyzed oxidative carbocyclization reactions were described by Backvall and coworkers [164-166]. Conjugaled dienes with appended al-lyl silane and stabilized carbanion nucleophiles undergo 1,4-carbochlorination (Eq. 36) and carboacetoxylation (Eq. 37), respectively. The former reaction employs BQ as the stoichiometric oxidant, whereas the latter uses O2. The authors do not describe efforts to use molecular oxygen in the reaction with allyl silanes however, BQ was cited as being imsuccessful in the reaction with stabihzed car-banions. Benzoquinone is known to activate Ti-allyl-Pd intermediates toward nucleophilic attack (see below. Sect. 4.4). In the absence of BQ, -hydride eUm-ination occurs to form diene 43 in competition with attack of acetate on the intermediate jr-allyl-Pd" species to form the 1,4-addition product 44. 

The best chemical and optical yields in the above reactions are obtained by using (S)- or (R)-proline. Some 19-norsteroids are prepared on an industrial scale from products of intramolecular aldol additions catalyzed by (S)-proline 68). 

Hydroamination of Alkynes The discovery of palladium-catalyzed intramolecular addition of amines to acetylene coupled with the spectacular contribution of Hutchings opened the door for the synthesis of several nitrogen heterocycles. The first study in this field was performed by Utimoto et al., who researched gold catalyzed intramolecular 6-exo-dig hydroamination. Tautomerization of the initial enamines allowed them to obtain imines, which were thermodynamically more stable [111] (Scheme 8.20). 

An intramolecular photocyclization catalyzed by copper(I) triflate provided a key step in a total synthesis of the ginseng sesquiterpenes a- and /J-panasinsene, (8) and (9). The unsaturated allylic alcohol (6) is cyclized by irradiation at 254 tun in the presence of CuOTf to a mixture of saturated alcohols, which is oxidized to the ketone 7. The ketone is inert to methylenetriphenylphosphorane, but can be converted into a 2 5 mixture of 8 and 9 by addition of mcthyllithium followed by dehydration.2... 

The latter transformation requires the use of a small amount of an acid or its ammonium salt. By using [Cp2TiMe2] as the catalyst, primary anilines as well as steri-cally hindered tert-alkyl- and sec-alkylamines can be reacted.596 Hydroamination with sterically less hindered amines are very slow. This was explained by a mechanism in which equlibrium between the catalytically active [L1L2Ti=NR] imido complex and ist dimer for sterically hindered amines favors a fast reaction. Lantha-nade metallocenes catalyze the regiospecific addition of primary amines to alkenes, dienes, and alkynes.598 The rates, however, are several orders of magnitude lower than those of the corresponding intramolecular additions. 

The competition between Michael addition of a,(3-unsaturated ketones and Diels-Alder reactions involving furan and 2-methylfuran is affected by the catalyst used. Methyl vinyl ketone gives the alkylation product with furan and 2-methylfuran in the presence of silica gel (88TL175). Bis(alkylated) products have also been obtained in reactions of 2-methylene-1,3-dicarbonyl compounds (90H(31)1699). An intramolecular proton catalyzed alkylation reaction of an a,(3-unsaturated ketone provided a straightforward synthesis of norpinguisone (90TL4343) and in the example shown in Equation (4) the cyclization reaction involved an a,(3-y,8-dienone (94TL4887). 

The 2-benzazepin-3-ones 259 have been made in moderate yields by sequential intramolecular acid-catalyzed addition followed by thiol elimination from the precursor phenylsulfanylacrylamides 258 (Scheme 33). The acrylamides 258 were prepared from reaction of the benzylamines 255 with the PNB-ester 256 to give the amides 257, and then N-methylation with Mel in the presence of potassium hydroxide and tetraethylammonium bromide, as a phase-transfer catalyst. Other noncyclized products were also observed depending on the structure of the A-aryl methyl group in 258 and on the nature of the solvent <2002H(57)1063>. 

The Pd-catalyzed hydrocarbonations of methyleneaziridines 14 do not proceed through the formation of a Jt-allylpalladium intermediates, instead via a chelation effect. The hydropalladation of methyleneaziridines with the Pd(II) hydride species 16, followed by reductive elimination gives the non-ring-opened products 15. It is noteworthy to mention that the palladium-catalyzed intermolecular or intramolecular addition of nitriles to carbon-carbon multiple bonds can be explained by the hydropalladation mechanism, except for the intramolecular addition to the C=C triple bond of alkynes (vide infra). 

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