Face selectivity

In the Sharpless epoxidation of divinylmethanols only one of four possible stereoisomers is selectively formed. In this special case the diastereotopic face selectivity of the Shaipless reagent may result in diastereomeric by-products rather than the enantiomeric one, e.g., for the L -(-(-)-DIPT-catalyzed epoxidation of (E)-a-(l-propenyl)cyclohexaneraethanol to [S(S)-, [R(S)-, [S(R)- and [R(R)-trans]-arate constants is 971 19 6 4 (see above S.L. Schreiber, 1987). This effect may strongly enhance the e.e. in addition to the kinetic resolution effect mentioned above, which finally reduces further the amount of the enantiomer formed. 

The liquid s pressure in the seal chamber holds the faces together and also provides a thin film of lubrication between the faces. This lubricant is the pumped product. The faces, selected for their low frictional eharaetcristies, are the only parts of the. seal in relative motion. Other parts would be in relative motion if the equipment is misaligned or with loose tolerance in the bearings. 

A versatile synthetic route to enantiomeric ally pure Diels-Alder adducts was deduced and found dependent on the application of enantiomerically pure 5-methoxy-174a (R=Me) and 5-(l-menthyloxy)-2(5//)-furanones 174b (R = menthyl), which were expected to undergo tt-face-selective cycloaddition with dienes. The reaction was effected by heating no Lewis acid catalysts were required (Scheme 55) (88JOC1127). 

For the performance of an enantioselective synthesis, it is of advantage when an asymmetric catalyst can be employed instead of a chiral reagent or auxiliary in stoichiometric amounts. The valuable enantiomerically pure substance is then required in small amounts only. For the Fleck reaction, catalytically active asymmetric substances have been developed. An illustrative example is the synthesis of the tricyclic compound 17, which represents a versatile synthetic intermediate for the synthesis of diterpenes. Instead of an aryl halide, a trifluoromethanesul-fonic acid arylester (ArOTf) 16 is used as the starting material. With the use of the / -enantiomer of 2,2 -Z7w-(diphenylphosphino)-l,F-binaphthyl ((R)-BINAP) as catalyst, the Heck reaction becomes regio- and face-selective. The reaction occurs preferentially at the trisubstituted double bond b, leading to the tricyclic product 17 with 95% ee. °... 

There are four main factors that affect the enantioselectivity of sulfur ylide-mediated reactions i) the lone-pair selectivity of the sulfonium salt formation, ii) the conformation of the resulting ylide, iii) the face selectivity of the ylide, and iv) betaine reversibility. 

In the case of sulfide 7 the bulky camphoryl moiety blocks one of the lone pairs on the sulfide, resulting in a single diastereomer upon alkylation. One of the conformations (29b) is rendered less favorable by non-bonded interactions such that conformation 29a is favored, resulting in the observed major isomer (Scheme 1.11). The face selectivity is also controlled by the camphoryl group, which blocks the Re face of the ylide. 

The high enantioselectivity observed was interpreted in terms of the face selectivity of the (Z)-enolate 59 (Scheme 1.20). The phenyl moiety is thought to stabilize the enolate through a n-n interaction and effectively shield its Re face such that the incoming ketone approaches preferentially from the Si face. 

In y-alkoxyfuranones the acetal functionality is ideally suited for the introduction of a chiral auxiliary simultaneously high 71-face selectivity may be obtained due to the relatively rigid structure that is present. With ( + )- or (—(-menthol as auxiliaries it is possible to obtain both (5S)- or (5/ )-y-menthyloxy-2(5//)-furanones in an enantiomerically pure form293. When the auxiliary acts as a bulky substituent, as in the case with the 1-menthyloxy group, the addition of enolates occurs trans to the y-alkoxy substituent. The chiral auxiliary is readily removed by hydrolysis and various optically active lactones, protected amino acids and hydroxy acids are accessible in this way294-29s-400. 

The diastereoselective intramolecular Michael addition of /(-substituted cyclohexcnoncs results in an attractive route to ra-octahydro-6//-indcn-6-ones. The stereogenic center in the -/-position of the enone dictates the face selectivity, whereas the trans selectivity at Cl, C7a is the result of an 6-exo-trig cyclization. c7.v-Octahydro-5//-inden-5-ones are formed as the sole product regardless of which base is used, e.g., potassium carbonate in ethanol or sodium hydride in THF, under thermodynamically controlled conditions139 14°. An application is found in the synthesis of gibberellic acid141. 

Various diastereoselective Michael reactions are based on y-bromo-, y-alkyl-, or y-alkoxy-2(5//)-furanones following the trans-face selectivity shown in Section 1.5.2.3.1.2. Thus the lithium enolates of esters such as ethyl propanoate, ethyl a-methoxyacetate and ethyl a-phenylacetate add to methoxy-2(5/f)-furanone with complete face selectivity269-273 (see Section 1.5.2.4.4.2.). 

Fischer alkenylcarbene complexes undergo cyclopentannulation to alkenyl AT,AT-dimethylhydrazones (1-amino-1-azadienes) to furnish [3C+2S] substituted cyclopentenes in a regio- and diastereoselective way along with minor amounts of [4S+1C] pyrrole derivatives. Enantiopure carbene complexes derived from (-)-8-(2-naphthyl)menthol afford mixtures of trans,trans-cycloipentenes and ds,ds-cyclopentenes with excellent face selectivity [75]. The mechanism proposed for the formation of these cyclopentene derivatives is outlined in Scheme 28. The process is initiated by nucleophilic 1,2-attack of the carbon... 

Furanones are a class of chiral dienophiles very reactive in thermal cycloadditions. For example, (5R)-5-(/-menthyloxy)-2-(5H)-furanone (28) underwent Diels Alder reaction with cyclopentadiene (21) with complete re-face-selectivity (Equation 2.10), affording a cycloadduct which was used as a key intermediate in the synthesis of dehydro aspidospermidine [27]. 

The ew face selectivities are still recent topics of electrocyclic reactions [39] and transition metal catalyzed reactions [40-47],... 

R2=C02CH3) exhibit little difference in face selectivity, i.e., syn selectivity when subject to NaBH symanti = 65 35 in 18d 62 38 in 18e) and DIBAL-H syn.anti = 66 34 in 18d 61 39 in 18e) reduction. The behavior of 18d and 18e is also consistent with orbital unsymmetrization, as in 19. On the other hand, Mehta et al. suggested the presence of significant electrostatic contributions from exo-electron-withdrawing groups, rationalizing the syn face selectivity in 18b [75]. 

Kinetic, spectroscopic, and enantioselectivity data provided strong evidence for a mechanism involving bimetallic catalysis. The configurational outcome depends upon the face selectivity of the enol approaching the Michael acceptor in 59 (Fig. 32). To differentiate between the enantiotopic faces, the catalyst has thus... 

Fig. 35 Explanation of the enantioselectivity by face selective olefin coordination...

Figure 3. Several strategies on controlling the shape of nanoparticles (a) organic molecules or polymers as capping agents, (b) inorganic molecules as face-selective catalysts, and (c) inorganic molecules as face-selective etchants.

The heterobimetallic asymmetric catalyst, Sm-Li-(/ )-BINOL, catalyzes the nitro-aldol reaction of ot,ot-difluoroaldehydes with nitromethane in a good enantioselective manner, as shown in Eq. 3.78. In general, catalytic asymmetric syntheses of fluorine containing compounds have been rather difficult. The S configuration of the nitro-aldol adduct of Eq. 3.78 shows that the nitronate reacts preferentially on the Si face of aldehydes in the presence of (R)-LLB. In general, (R)-LLB causes attack on the Re face. Thus, enantiotopic face selection for a,a-difluoroaldehydes is opposite to that for nonfluorinated aldehydes. The stereoselectivity for a,a-difluoroaldehydes is identical to that of (3-alkoxyaldehydes, as shown in Scheme 3.19, suggesting that the fluorine atoms at the a-position have a great influence on enantioface selection. 

The simplest nitroalkene, nitroethene, undergoes Lewis acid-promoted [4+2] cycloaddition with chiral vinyl ethers to give cyclic nitronates with high diastereoselectivity. The resulting cyclic nitronates react with deficient alkenes to effect a face-selective [3+2] cycloaddition. A remote acetal center controls the stereochemistry of [3+2] cycloaddition. This strategy is applied to synthesis of the pyrrolizidine alkaloids (+)-macronecine and (+)-petasinecine (Scheme 8.33).165... 

The readily available enantiopure acyclic hydroxy 2-sulfinyl butadiene 585 undergoes a highly face-selective Diels-Alder cycloaddition with PTAD to generate the densely functionalized cycloadduct 586 (Equation 84). The complete reversal of facial selectivity is observed when sulfonyl derivative 587 is treated with PTAD under identical conditions (Equation 85). These results demonstrate that the sulfinyl functionality is not just synthetically useful but also an extremely powerful element of stereocontrol for intermolecular Diels-Alder cycloadditions. On the other hand, the corresponding ( , )-hydroxy-2-sulfinyldienes treated with PTAD affords the cycloadducts in high yield but with moderate 7i-facial selectivity <1998CC409, 2005CEJ5136>. 

The heteroatom-assisted Diels-Alder reaction has emerged as an extremely powerful method for the preparation of complex heterocycles. In several cases, such reactions with TADs are described. For example, the reaction of vinyl pyrrolidone 594 with MTAD provides a 7 2 mixture of diastereomers 595 and 596 in 95% combined yield, showing only low face selectivity (Equation 88) <2005JOC5221>. 

The transition-state model of this reaction has been proposed as (1), based on X-ray analyses of single crystals prepared from Ti(OPr )4, (R,R)-diethyl tartrate (DET), and PhCON(OH)Ph and from Ti(OPr )4, and (R,R) N,/V -dibenzyltartramide.30-32 The Z-substituent (R2), located close to the metal center, destabilizes the desired transition state and decreases enantioselectivity (vide supra). When the Z-substituent is chiral, face selection induced by the substituent strongly affects the stereochemistry of the epoxidation, and sometimes reversed face selectivity is observed.4 In contrast, the. E-substituent (R1) protrudes into an open space and E -allylic alcohols are generally good substrates for the epoxidation. 

The Paterno-Buchi photocycloaddition between carbonyl compounds and furans was first described in 1965 (equation 6)80. This report noted that only the head-to-head product 171 was formed, and that high exo face selectivity was exhibited. Subsequent to this and other early reports, this reaction has been systematically explored by several groups, owing largely to the various ways in which the 2,7-dioxabicyclo[3.2.0]hept-3-ene ring system can be exploited730,81. 

Benzonitrile oxide, generated by dehydrochlorination of benzohydroximoyl chloride, undergoes regio- and face-selective cycloadditions to 6,8-dioxabicyclo [3.2.1]oct-3-ene 108a yielding a 4 1 mixture of 4,5-dihydroisoxazoles 109 and 110. Both products have exo-stereochemistry, resulting from the approach of the nitrile oxide from the face opposite to the the methyleneoxy bridge. Structures of the adducts were determined by 1 H NMR spectroscopy and, in the case of compound 109, by X-ray diffraction analysis (275). 

Face selectivity in the 1,3-dipolar cycloaddition reactions of benzonitrile oxide and its p-substituted derivatives with 5-substituted adamantane-2-thiones,... 

Addition of distannane to alkenes has been achieved only with strained cyclopropenes (Equation (60)).158 3,3-Disubstituted cyclopropenes undergo highly face-selective distannation in the presence of the palladium-isocyanide complex to afford m-adducts. 

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