Convex face

In transforming bis-ketone 45 to keto-epoxide 46, the elevated stereoselectivity was believed to be a consequence of tbe molecular shape — tbe sulfur ylide attacked preferentially from tbe convex face of the strongly puckered molecule of 45. Moreover, the pronounced chemoselectivity was attributed to tbe increased electropbilicity of the furanone versus the pyranone carbonyl, as a result of an inductive effect generated by tbe pair of spiroacetal oxygen substituents at tbe furanone a-position. ... 

An unusual solvent system was chosen for the intramolecular reductive alkylation of the masked amino ketone (15). The purpose of the strongly acid system was to prevent cyclization of the deblocked amino ketone to 16, further hydrogenation of which gives the unwanted isomer 17 by attack at the convex face. The desired opposite isomer can be obtained by reduction of 16 with UAIH4 (52). 

The relationship between 20 and reserpine (1) is close like reserpine, intermediate 20 possesses the linear chain of all five rings and all six stereocenters. With the exception of the 3,4,5-tri-methoxybenzoate grouping, 20 differs from reserpine (1) in one very important respect the orientation of the ring C methine hydrogen at C-3 in 20 with respect to the molecular plane is opposite to that found in reserpine. Intermediate 20 is a reserpate stereoisomer, epimeric at position 3, and its identity was secured by comparison of its infrared spectrum with that of a sample of (-)-methyl-O-acetyl-isoreserpate, a derivative of reserpine itself.9 Intermediate 20 is produced by the addition of hydride to the more accessible convex face of 19, and it rests comfortably in a conformation that allows all of the large groups attached to the D/E ring skeleton to be equatorially disposed. 

Our journey begins with the photo-induced union of 3,4-dimethylfuran (19) and / -(benzyloxy)-propanal (18) (see Scheme 5). Irradiation of a solution of these two simple, achiral compounds in benzene with a 450 W Hanovia lamp equipped with a vycor filter results in the exclusive formation of head-to-head, exo photoadduct 17 in 63% yield. As a cw-fused dioxabicyclo[3.2.0]heptene system, intermediate 17 possesses a folded molecular framework to which access is obstructed on the concave face. In the presence of mCPBA, the less hindered convex face of the enol ether double bond is oxidized in a completely diastereoselective fashion, affording intermediate 16 in 80% yield after regioselective opening of... 

The wide variety of methods available for the synthesis of orga-noselenides,36 and the observation that the carbon-selenium bond can be easily cleaved homolytically to give a carbon-centered radical creates interesting possibilities in organic synthesis. For example, Burke and coworkers have shown that phenylselenolactone 86 (see Scheme 16), produced by phenylselenolactonization of y,S-unsaturated acid 85, can be converted to free radical intermediate 87 with triphenyltin hydride. In the presence of excess methyl acrylate, 87 is trapped stereoselectively, affording compound 88 in 70% yield 37 it is noteworthy that the intramolecular carbon-carbon bond forming event takes place on the less hindered convex face of bicyclic radical 87. 

Now that the allylic oxidation problem has been solved adequately, the next task includes the introduction of the epoxide at C-l and C-2. When a solution of 31 and pyridinium para-tolu-enesulfonate in chlorobenzene is heated to 135°C, the anomeric methoxy group at C-l 1 is eliminated to give intermediate 9 in 80% yield. After some careful experimentation, it was found that epoxy ketone 7 forms smoothly when enone 9 is treated with triphenyl-methyl hydroperoxide and benzyltrimethylammonium isopropoxide (see Scheme 4). In this reaction, the bulky oxidant adds across the more accessible convex face of the carbon framework defined by rings A, E, and F, and leads to the formation of 7 as the only stereoisomer in a yield of 72%. 

Bergman cycloaromatization 17, 523 f., 528 biaryl coupling -.intramolecular 516f., 519 bicyclic system -, concave face 59 -, convex face 59 bicyclo[3.3.0] system 221 f. bicyclo[4.2.0] system 221 f. bidentate ligands 680 f. 

Allylations of certain bicyclic A-acyliminium ions occur with complete stereoselectivity, as a result of stereoelectronically favored axial attack at the sterically less hindered convex face, independent of the stereochemistry of the acetoxy substituent in the first example. Thus, on... 

The compact bicyclic lactams 15 and 16 are examples of chiral systems that show high facial selectivity. Interestingly, 15 is alkylated from the convex face. When two successive alkylations are done, both groups are added from the endo face, so the configuration of the newly formed quaternary center can be controlled. The closely related 16 shows exo stereoselectivity. 100... 

The product of the reaction in Entry 8 was used in the synthesis of the alkaloid pseudotropine. The proper stereochemical orientation of the hydroxy group is determined by the structure of the oxazoline ring formed in the cycloaddition. Entry 9 portrays the early stages of synthesis of the biologically important molecule biotin. The reaction in Entry 10 was used to establish the carbocyclic skeleton and stereochemistry of a group of toxic indolizidine alkaloids found in dart poisons from frogs. Entry 11 involves generation of a nitrile oxide. Three other stereoisomers are possible. The observed isomer corresponds to approach from the less hindered convex face of the molecule. 

Some examples of conjugate addition reactions of allylic silanes are given in Scheme 9.5. Entries 1 to 3 illustrate the synthesis of several (3-allyl ketones. Note that Entry 2 involves the creation of a quaternary carbon. Entry 4 was used in the synthesis of a terpenoid ketone, (+)-nootkatone. Entry 5 illustrates fluoride-mediated addition using tetrabutylammonium fluoride. These conditions were found to be especially effective for unsaturated esters. In Entry 6, the addition is from the convex face of the ring system. Entry 7 illustrates a ring closure by intramolecular conjugate addition. 

Schreiber and his coworkers have published extensively over the past decade on the use of this photocycloaddition for the synthesis of complex molecules730 81. Schreiber was the first to recognize that the bicyclic adducts formed in these reactions could be unmasked under acidic conditions to afford threo aldol products of 1,4-dicarbonyl compounds (175 to 176) (Scheme 40). The c -bicyclic system also offers excellent stereocontrol in the addition of various electrophilic reagents (E—X) to the enol ether of these photoadducts on its convex face (175 to 177). This strategy has been exploited in the synthesis of a variety of architecturally novel natural products. 

Efficient synthesis of the mycotoxin asteltoxin 189 was accomplished beginning with the cycloaddition between 3,4-dimethylfuran and 3-benzyloxypropanal, which furnished pho-toaldol 183 in 63% yield (Scheme 42)84. Epoxidation from the convex face of this adduct, with subsequent epoxide opening, afforded 184, which was then elaborated through a series of steps to 185. The side chain was introduced via lithiosulfoxide 186 to furnish, after double sigmatropic rearrangement, 187. Hydrolysis of this afforded 188, which was oxidized and elaborated to 189 in two steps. 

Pyramidalization is also a well-established indicator of increased reactivity of alkenes where the 7r-type HOMO makes the major contribution to the reaction.12 This increased reactivity is specific to the more open (convex) face, and contributes to the well-known exo-selectivity of attack on bicyclo[2,2,l]hept-2-enes [60]. The electron density distribution of a derivative of [60] showed a measurable displacement of the electron-density maximum of the double bond in the exo direction (Irngartinger et al.,... 

In most cases a clear maximum gap is revealed (here the gap between the second and the third bar). The atomic environment is then constructed with the atoms to the left of this gap (8 + 6 in the example of CsCl). To avoid in particular cases bad or ambiguous descriptions, however, a few additional rules have been considered. When for instance two (or more) nearly equal maximum gaps were observed, a selection was made in order to keep, in a given structure type, the number of different AET as small as possible. A convexity criterion for the environment polyhedron was also considered. The coordination polyhedron has to be defined as the maximum convex volume around only one central atom enclosed by convex faces with all coordinating faces lying at the intersections of at least three faces. This rule was especially used where no clear maximum gap was detectable. 

Pentadiene 36 and isoprene (37) gave with 34a exclusively the regioisomers 39 and 40, respectively. Bicyclic methylenecyclopropanes 34a and 34b gave stereospecifically the isomers 38a and 38b deriving from the attack on the convex face of the methylenenorcarane 34a (or 34b). The reaction yields were generally good, but obtained with an excess of the diene. Only 34c gave 38c in 85% yield in the presence of only one molar equivalent of diene 35 [14]. 

A good example of clearable and non-clearable stereocentres is found in the two following stereoisomers of bicylo[3.3.0]octan-2-one, in which the shape of the molecule forces the attack of the nucleophile to the carbonyl group from the convex face (attack at the (3-face). 

The 1,2-carbonyl transposition takes place through the enJo-epoxide 18 easily prepared through the tosylhydrazone 16, followed by regioselective cleavage to the less substituted double bond (17) with 2 equivalents of methyllithium [4] and epoxidation with MCPBA in chloroform from the more accesible convex face of the decalin system. 

In practice (Scheme 13.3.3), the reduction of hydroxyketone 4 with either metal hydrides or sodium in wet ether gave only one compound to which the structure 3b (X = OH) was assigned (attack on the convex face of the tricyclic system). 

One way in which the Z-a,P-unsaturated carbonyl functionality could be exploited would be via its incorporation into lactone 17. It could be predicted with some confidence that external reagents would attack the bicyclic lactonic system from its convex face. Such an a attack by osmium tetroxide would provide the correct 7,8-erythro diol stereochemistry required to reach NeuSAc. This anticipation turned out to be well founded. 

The enolate generated by reaction of lactone 88 with lithium diisopropylamide (LDA) is quenched with an excess of methyl iodide to give methyl lactone 89 in excellent yield. As expected, the electrophilic attack is stereoselective for the less sterically hindered convex face of the lactone enolate, giving the product with the desired 7iJ-stereochemistry with greater than 95 5 selectivity (Equation 22) <1997TL3817>. 

A concave and a convex diastereoface may be distinguished, and it is apparent from ketone 7 that steric crowding is much more pronounced on the concave face. Thus, attack occurs from the convex face with high selectivity33. A variation of this principle is when the reagent adds to an unsaturated carbon at the ring fusion. 

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