Diastereoselectivity 6-membered ring

Only a few reactions are known for this subsection. In the first two examples complete diastereoselectivity is observed, owing to the favorable cis ring junction of the newly formed five- or six-membered ring with the existing five-membered ring. 

Consecutive Michael additions and alkylations can also be used for the diastereoselective synthesis of 5- and 6-membered ring systems. For instance when 6-iodo-2-hexenoates or 7-iodo-2-heptenoates are employed the enolate of the Michael adduct is stereoselectively quenched in situ to provide the cyclic compound with trans stereochemistry (>94 6 diastereomeric ratio). As the enolate geometry of the Michael donor can be controlled, high stereoselectivity can also be reached towards either the syn or anti configuration at the exocyclic... 

Palladacycles are defined as compounds with a Pd-C CT-bond with the Pd being stabilized by one or two neutral donor atoms, typically forming 5- or 6-membered rings [51]. Ferrocenyl palladacycles constitute a particularly attractive catalyst class partly due to the element of planar chirality. The first diastereoselective cyclopallada-tion of a chiral ferrocene derivative was reported in 1979 by Sokolov [52, 53]. 

Chakraborty has described the highly diastereoselective. Barrero and his group developed an approach to functionalized six-membered rings with exocyclic olefins from a-oxygenated derivatives of geraniol. The diastereo-selectivity observed is reasonable and thus the method holds promise for natural product synthesis [105]. 

Cyclization to six-membered rings (Eq. 15) provided modest diastereoselectivity and required the use of bulkier PhMeSiH2 to prevent olefin hy-drosilylation. Propargyl and homopropargyl amines 94 afforded a variety of heterocycles (Scheme 21), if the catalyst was added slowly over the reaction course to diminish side reactions resulting from metal coordination to the basic amine [56]. The reaction procedure was extended to the diastereoselect-ive bicyclization of dienyne substrate 95, giving 96 as product in a cascade fashion (Eq. 16) [57]. 

This regio- and stereochemistry in these reactions can be accounted for as shown in Scheme 17.26 When coordinating electrophiles like ketones and aldehydes are used, the equilibrium between ij1- and 3-allyl complexes shifts to rj1, resulting in the formation of the least substituted -complex 52 preferentially. Carbon-carbon bond formation takes place via a six-membered ring transition state 53, leading to the formation of the branched homoallylic alcohols 54 with //-diastereoselectivity. 

In a related cobalt-catalyzed transformation, 1,3-dienes tethered to ally lie ethers engage in Et2AlCl-mediated reductive cyclization.463 Exposure of benzylic ether 22a to Co(acac)3-PPh3 in the presence of Et2AlCl results in formation of divinylcyclopentane 22b with excellent /raar-diastereoselectivity. As demonstrated by the conversion of 23a to 23b, this method is also applicable to the stereocontrolled formation of six-membered rings (Scheme 16). 

In contrast to the nickel-organozinc catalyst system, which induces /3,/3-coupling of bis(enones), the use of cobalt(ll) catalysts in the presence of silane results in a,/3-coupling to provide products of reductive Michael cyclization.48,48a,48b Both five- and six-membered ring products 26b and 25d are formed in good yields and with complete diastereoselection. The choice of silane is critical. Whereas exposure of bis(enone) 25a to Co(dpm)2... 

Though several intermolecular catalytic reductive aldol additions are reported, corresponding reductive cyclizations have received less attention. The first reported reductive aldol cyclization involves use of a (diketonato)cobalt(ll) precatalyst in conjunction with PhSiHj as terminal reductant.48,486 The reductive cyclization is applicable to aromatic and heteroaromatic enone partners to form five- and six-membered rings. As demonstrated by the reductive cyclization of mono-enone mono-aldehyde 65a to afford aldol 65b, exceptionally high levels of ty -diastereoselectivity are observed. Interestingly, exposure of the substrate 65a to low-valent nickel in the presence of excess Et2Zn provides the isomeric homoaldol cyclization product 65c via reductive coupling to the enone /3-position (Scheme 43).47a... 

The [4+ 4]-cycloaddition reaction of tethered bis-dienes has been used by Wender and co-workers in total synthesis as exemplified in syntheses of ( )-salsolene oxide and (-l-)-asteriscanolide (Scheme 28). In the synthesis of ( )-salsolene oxide, a nickel(0)-catalyst cleanly effects the cycloaddition of the two conjugated dienes in compound 93 to afford the bicyclo[5.3.1]undecadiene in a good yield and with moderate selectivity.99 The first synthesis of (-l-)-asteriscanolide was accomplished in only 13 steps. The key [4+ 4]-cycloaddition reaction efficiently set the requisite eight-membered ring of (-l-)-asteriscanolide in good yield and with excellent diastereoselectivity.100 The diastereoselective [4 + 4]-cycloaddition has also been applied to the synthesis of the core ring system found in several sesterterpenes such as the ophiobolins (Scheme 28).101... 

While the notion that the alkoxides derived from aliphatic alcohols are poor nucleophiles toward 7r-allylmetal complexes has prevailed over the years, much progress made in the recent past has rendered the transition metal-catalyzed allylic alkylation a powerful method for the O-allylation of aliphatic alcohols. In particular, owing to the facility of five- and six-membered ring formation, this process has found extensive utility in the synthesis of tetrahydrofurans (THFs) (Equation (29))150-156 and tetrahydropyrans (THPs).157-159 Of note was the simultaneous formation of two THP rings with high diastereoselectivity via a Pd-catalyzed double allylic etherification using 35 in a bidirectional synthetic approach to halichondrin B (Equation (30)).157 The related ligand 36 was used in the enantioselective cyclization of a Baylis-Hillman adduct with a primary alcohol (Equation (31)).159... 

Hydrosilylation of 1,6-dienes accompanied by cyclization giving a five-membered ring system is emerging as a potential route to the synthesis of functionalized carbocycles.81,81a,81b 82 As its asymmetric version, diallylmalonates 86 were treated with trialkylsilane in the presence of a cationic palladium catalyst 88, which is coordinated with a chiral pyridine-oxazoline ligand. As the cyclization-hydrosilylation products, //ww-disubstituted cyclopentanes 87 were obtained with high diastereoselectivity (>95%), whose enantioselectivity ranged between 87% and 90% (Scheme 25).83 83a... 

Six-Membered Ring (exo-Cyclic). The diastereoselective alkylation reactions of exo-cyclic enolates involving 1,2-asymmetric inductions are anti-inductions. In Scheme 2-2, there are two possible enolate chair conformations in which the two possible transition-state geometries lead to the major diaster-eomer 9e (where the substituent takes the equatorial orientation). However, for the case in which R = methyl and X = alkoxyl or alkyl, one would expect the... 

The diastereoselective alkylation reaction of endo-cyclic five-membered ring enolates exhibits good potential for both 1,3- and 1,2-asymmetric induction. In Scheme 2-6, the factor controlling the alkylation transition state is steric rather than stereoelectronic, leading to an auh-induction.13... 

Another possibility to increase the diastereoselectivity in an asymmetric synthesis can arise from different thermodynamic stabilities of the diasteieoisomeric products. If the thermodynamic stabilities of these are different enough, then, under conditions of equilibrium, a complete conversion of the less stable into the more stable can be achieved. For example, the diastereoselective hydrogenation of naphthalene derivates over Pd/C catalyst leads to a mixture of dihydronaphtalenes in which the cA-isomer predominates. The conversion of this isomer into the tram occurs by changing the properties of the reaction medium, namely by equilibration with a base. For such a purpose, NaOMe in IHF can be used [263], Generally, such an increase in stability in the six-membered rings can result from a rearrangement of the substituents from an axial to an equatorial position. 

---