Cyclization reaction diastereoselective

The Lewis acid of choice for most of the cyclization reactions is ethylaluminum dichloride, because of its exceptional properties it is a mild Lewis acid, and, as an organometallic compound, can serve as a proton sponge , and thereby inhibit competitive protodesilyla-tion37. The desired precursors reacted smoothly with 1.1 equivalents of ethylaluminum dichloride in toluene or dichloromethane at low temperature to generate diastereoselectively the desired spiro[4.5]decanones38. 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

Scheme 6 Diastereoselectivity within the reductive cyclization reaction...

Additions of stabilized carbanions to imines and hydrazones, respectively, have been used to initiate domino 1,2-addition/cyclization reactions. Thus, as described by Benetti and coworkers, 2-subshtuted 3-nitropyrrolidines are accessible via a nitro-Mannich (aza-Henry)/SN-type process [165]. Enders research group established a 1,2-addition/lactamization sequence using their well-known SAMP/ RAMP-hydrazones 2-308 and lithiated o-toluamides 2-307 as substrates to afford the lactams 2-309 in excellent diastereoselectivity (Scheme 2.72) [166]. These compounds can be further transformed into valuable, almost enantiopure, dihydro-2H-isoquinolin-l-ones, as well as dihydro- and tetrahydroisoquinolines. 

A lanthanide-mediated, sequential hydroamination/C-C cyclization reaction served to prepare the benzo[ ]quino-lizine derivative 358 from precursor 357, using a Nd species as a catalyst (Equation 12). This cascade process proceeded in good yield and with high diastereoselectivity <2003T10581>. 

High diastereoselectivity occurs in the addition of lithiated methoxyallene to chiral cyclic nitrones. The hydroxylamines obtained can be easily transformed into derivatives of 1,2-oxazine hydroxylamine, which are products of a novel [3 + 3] cyclization reaction (Scheme 2.182) (646, 647). 

Photoinduced electron transfer promoted cyclization reactions of a-silyl-methyl amines have been described by two groups. The group of Pandey cyclized amines of type 135 obtaining pyrrolidines and piperidines 139 in high yields [148]. The cyclization of the a-silylated amine 140 leads to a 1 1 mixture of the isomers 141 and 142 [149]. The absence of diastereoselectivity in comparison to analogous 3-substituted-5-hexenyl radical carbocyclization stereochemistry [9] supports the notion that a reaction pathway via a free radical is unlikely in this photocyclization. The proposed mechanism involves delocalized a-silylmethyl amine radical cations as reactive intermediates. For stereochemical purposes, Pandey has investigated the cyclization reaction of 143, yielding... 

Intramolecular addition of hydroxylamines and hydroxamic acids to the non-activated double bonds is possible through oxidative cyclization. Reaction of O-Acyl fi,y-unsaturated hydroxamates (e.g. 56, equation 38) with bromine provides 3,4-substituted iV-hydroxy -lactams such as 57 with high diastereoselectivity. Analogous reaction of O-benzyl hydroxylamine 58 (equation 39) with iodine results in five-membered cyclization with 2 1 ratio of diastereomers. ... 

The use of Lewis acids in controlling the stereoselective outcome of radical cyclization reactions has been explored, in particular the effect of aluminium-based Lewis acids using low temperature Et3B/Bu3SnH-initiated procedures.171,172 For example, cyclization of propargyl ether (78) or allyl ether (79) in the presence of Lewis acid (80) can completely reverse the normal selectivity (Scheme 34).171 The effect of aluminium Lewis acids on the diastereoselectivity of 6-exo cyclization of unsaturated chiral menthol esters has been studied.172 Cyclization at low temperature in the presence of the Lewis acid MAD modified the de of the reaction from 31 to 98%. 

A Lewis-acid-mediated intramolecular cyclization of allenyl stannane 344 furnishes 2,6- //-tetrahydropyran as the major product, the stereochemistry of which can be switched to syn with moderate effect if a propargylstannane 345 is used as a substrate (Equation 147, Table 16) <1996TL3059>. The stereoselectivity observed in an analogous system, the intramolecular cyclization of y-alkoxyallyl stannanes 346 with a tethered aldehyde, can be controlled by changing the geometry of the alkene (Scheme 83) <1997JOC7439>. y-Alkoxyallyl stannanes are also known to cyclize both diastereoselectively and enantioselectivity, by incorporation of both a chiral auxiliary and a chiral catalyst respectively into the reaction <1999JOC4901>. 

A similar radical cyclization reaction of unsaturated amino acid derivatives has been recently reported by Steckhan et al. [36]. The PET-catalyzed cyclization reaction proceeds under mild conditions using 9,10-dicyanoanthracene (DCA) as sensitizer and biphenyl (BP) as co-sensitizer (Sch. 14). The diastereoselectivity of the cyclization step was found to be moderate to high depending on the substitution pattern of the starting material. In almost all cases examined, the raws-diastereoisomer was predominately formed. 

Langer and coworkers reported on the [3+ 2]-type C,0-cyclodialkylation of cyclohexane-1,3-dione dianion with l,4-dibromo-2-butene (Scheme 25)39. The formation of the tetrahydrofuran-fused cyclohexenone can be explained by a regioselective attack of the terminal carbon of the dianion on the l,4-dibromo-2-butene and subsequent Sy2 -type cyclization. This reaction proceeded with a high degree of diastereoselectivity. An excellent review of this type of cyclization reaction is now available elsewhere40. 

The mathematical description of this and related reaction schemes are complex and will not be discussed here. To verify the analysis of the stereoselection at the steady state experimentally, diastereoselective radical cyclization reactions were selected. Although face-selective radical cyclizations are much more common than the group-selective counterparts [4], several model compounds were suggested by Curran et al [2]. Molecules which have two radical precursors and one radical acceptor group such as 9 were selected to provide experimental verification... 

Stereoselective syntheses of the tetrahydrofuran nucleus by alkoxyl radical cyclizations have been reviewed by Hartung <2001EJ0619>. Cyclizations of C-centered radicals are also freqently employed in the synthesis of tetrahydrofurans. In tandem radical cyclizations, high diastereoselectivities can be obtained. Hoffmann has shown that an a-silyl effect can be exploited to obtain enhanced diastereoselectivities in such reactions (Equation 94) <1997T8401>. A tra r-selective synthesis of 2,3-disubstituted tetrahydrofurans also makes use of a vinylsilane group <1994TL5837>. 

The carbon-carbon unsaturated substrates have now expanded from aminoalkenes to aminoalkynes, aminoallenes, and aminodienes, and the hydroamination/cyclization reactions of these substrates have produced functionalized nitrogen-containing heterocycles. It is worth noting that the aminoallene hydroamination/cyclization reactions are highly diastereoselective, and can provide concise routes to the synthesis of some natural products (Figure 8.38) [126]. 

Diazafulvene 424 reacts with alkenylcarbenes 425 through a formal [64-3] heterocyclization in a regio- and stereoselective manner to afford dihydroimidazo[l,2- ]pyridines 426. When enyne carbenes are treated with diazafulvene 424, consecutive and diastereoselective [64-2]/cyclopentannulation cyclization reactions take place affording new polycyclic complex systems 429 that can be appropriately demetallated to the corresponding imidazole-based fused systems. Finally, enyne carbenes undergo consecutive [64-2]/[54-l] cyclization reactions with diazafulvene 424 and rt-butyl-NC to yield tetracyclic adducts 432 (Scheme 102) <2006CEJ3201>. 

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