Intramolecular enantioselective

As mentioned above (66, 393), (see Scheme 3.150) silylation followed by intramolecular enantioselective cycloaddition with five-membered cyclic nitronates, containing the hydroxyl group at C-4, can produce chiral polycyclic structures (293), which are direct precursors of chiral hydroxyamino acids (294) and aminopolyols (295) (Scheme 3.179). 

Intramolecular cyclopropanation has a noteworthy advantage. Unlike intermolecular asymmetric cyclopropanation, the intramolecular reaction produces only one diastereomer due to geometric constrains on the fused bicyclic products. Doyle has extensively studied the intramolecular enantioselective reactions of a variety of alkenyl diazoacetates catalyzed by chiral rhodium carboxamides 198 and 200 and has achieved excellent results. 

Allyl carbonate 81 reacts with primary and secondary amines 82 to afford branched aUylic amination products 83 under the influence of a [IrCl(cod)]2/ P(OPh)3 catalyst (Equation 10.17) [38]. In this reaction, alcohols such as ethanol and methanol proved to be the best solvents, while both intermolecular and intramolecular enantioselective aUylic aminations were reported by using chiral phosphoramidites as ligands [39]. The aUylic amination of (Zj-2-noneyl carbonate 85 with 82 in the presence of [IrCl(cod)]2 and P(OPh)3 afforded Z-linear aUylic amines (Equation 10.18) [38]. In this reaction, the Z-geometry of 85 was completely retained. 

A very useful extension of the de Mayo reaction has been recently introduced by Blechert et al. (Scheme 6.26) [78]. The retro-aldol fragmentation was combined with an intramolecular enantioselective allylation (asymmetric ring-expanding allylation) catalyzed by a chiral Pd complex. Bicycloheptane 68, for example, was accessible by intermolecular [2 + 2]-photocycloaddition of cyclopentenone 67 with allene. Further transformation in the presence of Pd2(dba)3 (dba = dibenzylideneacetone) and the chiral oxazoline ligand 69 (tBu-phox) resulted in the enantioselective formation of cycloheptadione 70. 

This domino Wacker-Heck reaction is the key step of this total synthesis. In the presence of catalytic amounts of Pd(OTFA)2, the chiral ligand (S,S)-Bn-BOXAX (5) and j -benzoquinone (13) as reoxidant, phenol 19 first undergoes an intramolecular enantioselective Wacker oxidation and then reacts with methyl vinyl ketone (9) in a Heck reaction to afford chroman 22 with part of the vitamin E side chain in 84 % yield with 97 % ee. 

The general procedure for a silane-terminated intramolecular enantioselective Heck reaction is exemplified by Scheme 3-60 [61a,b, 259]. A mixture of [Pd2(dba)3 - CHCI3] (0.025 mmol,... 

Scheme 5.56 Intramolecular enantioselective hydroarylation catalyzed by chiral Cp—Rh complexes reported hy Cramer.

Inter- and intramolecular enantioselective carbolithiation reactions in the presence of a chiral ligand for lithium, such as (—)-sparteine 13BJ0313. New application progress of chiral bis(oxazoline) ligands in asymmetric catalysis 13CJ02283. 

In 1990, Cabri el al. [40a] reported that the precursor Pd(OAc>2 associated with a biden-tate P P ligand as dppp (1,3-bis-diphenylphosphinopropane) appeared to be more efficient than PPhs in Mizoroki-Heck reactions performed from aryl Inflates and enol ethers (electron-rich alkenes) moreover, the regioselectivity in favour of the a-arylated alkenes was improved to 100%. Since that time, dppp associated with Pd(OAc)2 has been used extensively to catalyse Mizoroki-Heck reactions and to investigate the factors that control the regioselectivity [Ig, 40]. The chiral bidentate (7 )-Binap (2,2 -bis(diphenylphosphino)-1,1-binaphthyl) associated with Pd(OAc)2 has also been used by Shibasaki and coworkers [2b,d,41a] and Overman andPoon [41b] in intramolecular enantioselective Mizoroki-Heck reactions (also, see Link [2f] for an authorative review on the Overman-Shibasaki chemistry), as well as by Hayashi and coworkers [2a, 41c,d] to control the regioselectivity and enantioselectivity of intermolecular Mizoroki-Heck reactions performed from cyclic alkenes (see Schemes 1.3 and 1.2 (Z = O) respectively). 

Intramolecular Enantioselective Mizoroki Heck Reactions 44 / Table 12.1 Intramolecular Mizoroki-Heck reaction of enantioenriched o-iodoanilides... 

Ripa, L. and Hallberg, A. (1997) Intramolecular enantioselective palladium-catalyzed Heck arylation of cyclic enamides. J. Org. Chem., 62, 595-602. 

The intramolecular enantioselective Rauhut-Currier reaction [295] generates optically active cycloalkenes from acyclic precursors bearing two tethered Michael acceptors. In 2(X)7, Miller et al. reported the first organocatalyzed intramolecular cyclization of symmetrical bis(a,P-unsaturated ketones) to afford in good yields... 

Intramolecular enantioselective arylation reactions of ketones 29 were described by Lu (Scheme 8.10) [27]. The cationic (BINAP)-palladiumhydroxo complex 30 works in combination with a basic anion-exchange resin as an additive to afford optically active cycloalkanols 31 in high yields and enantioselectivities. 

Also on record there is an interesting example of Rh-catalysed intramolecular enantioselective catalytic Diels-Alder reaction (Scheme 8.25). ... 

Dong and co-workers reported the synthesis of chiral phthalides (76) by intramolecular enantioselective ketone hydroacylation. Excellent yields and exceedingly high optical purities of 76 were found. Good tolerance to substitutions at positions 4, 5 or 6 (but not at 3) of the aromatic ring of 75 was observed. To achieve high enantioselectivities and avoid undesired reactions, an appropriate choice of the silver salt was found to be crucial. 

Toste has described the intramolecular enantioselective hydroamination of y- and 6-aUenyl sulfonamides catalyzed by enantiomerically pure bis(gold) phosphine complexes [42]. For example, treatment of the terminally-disubstituted y-allenyl sulfonamide 59 with a catalytic amount of [(R)-3,5-xylyl-binap](AuOPNB)2 (OPNB =p-nitrobenzoate) formed protected pyrrolidine 60 in 88% yield with 98% ee (Eq. (11.34)). Likewise, treatment of 6-allenyl sulfonamide 61 with a catalytic amount of [(JJ)-Cl-MeObiphep](AuOPNB)2 in nitromethane at 50 °C for 24h formed 2-alkenyl piperidine 62 in 70% isolated yield with 98% ee (Eq. (11.35)). Realization of high enantioselectivity in this protocol required employment of both a terminally disubstituted allene and a sulfonamide nucleophile. 

In early 2007, Widenhoefer and Zhang reported the gold(I)-catalyzed intramolecular enantioselective hydroalkoxylation of y- and 6-hydroxyallenes [106]. For example, reaction of 2,2-diphenyl-4,5-hexadienol with a catalytic 1 2 mixture of [(S)-63]Au2Cl2 [(S)-63 = (S)-DTBM-MeObiphep] and AgOTs at 20 °C in toluene for 18h led to isolation of 4,4-diphenyl-2-vinyltetrahydrofuran in 67% yield with 93% ee (Eq. (12.35)). This protocol was also effective for the enantioselective 6-e%o-hydro-alkoxylation of 6-hydroxyallenes to form tetrahydropyrans. Gold(I)-catalyzed cycli-zation of y-hydroxyallenes that possessed an axially chiral 1,3-disubstituted allenyl moiety occurred with high enantioselectivity/low diastereoselectivity in a catalyst-... 

Toste and coworkers have developed effective gold(I)-catalyzed protocols for the intramolecular enantioselective hydroalkoxylation of y- and 8-hydroxy allenes employing chiral, enantiomerically pure silver salts [107]. For example, treatment of y-hydroxy allene 66 with a catalytic 1 2 mixture of the achiral bis(gold) complex (dppm)Au2Cl2 [dppm = bis(diphenylphosphino)methane] and chiral silver phos-phonate Ag-(J )-67 in benzene at room temperature led to isolation of 2-alkenyl tetrahydrofuran 68 in 90% yield with 97% ee (Eq. (12.36)). A combination of chiral bis(gold) complex with a chiral silver salt proved effective for terminally unsubstituted allenyl alcohols. For example, reaction of 5,6-heptadienol catalyzed by a mixture of [(S,S)-DIPAMP]Au2Cl2 [DIPAMP = l,2-ethanediylbis[(2-methoxyphenyl) phenylphosphine] and Ag-(J )-67 gave 2-vinyltetrahydropyran 69 in 96% yield with 92% ee (Eq. (12.37)). 

A particularly interesting example was reported by Yang et al. [53], who described an intramolecular enantioselective cascade reaction of 56. Initial reactions using... 

The intramolecular enantioselective aminofluorination of unactivated olefins, such as (1), has been attained by using the chiral iodo(III) difluoride (5) with <88% ee (Scheme 1). The reaction is believed to proceed via an intramolecular aziridination (1) (2) - (3), followed by a nucleophilic attack with to produce (4). A regio-selective aminofluorination of styrenes ArCH=CH2 with p-xylene IFj and TsNHR... 

Scheme 14.3 Intramolecular enantioselective arylation of carbonyl compounds.

Liu W-J, Chen Z-L, Chen Z-Y, Hu W-H. Dirhodium catalyzed intramolecular enantioselective C—H insertion reaction of A-cumyl-A-(2-/)-anisylethyl)diazoacetamide synthesis of (—)-rolipram. Tetrahedron Asymm. 2005 16 1693-1698. 

Boron Intramolecular, enantioselective hydroboration of the normally unreactive A -het-erocyclic carbene (NHC)-boranes, such as (84), has been attained by B-H activation in the presence of rhodium(I) catalyst and the chiral diphosphine ligand (86). The cyclic boranes (85) thus obtained were of <98% eeP... 

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