Asymmetric induction in intramolecular

Asymmetric Induction in Intramolecular Rhodium(l)-Catalyzed [4-1-2] Reactions... 

Asymmetric induction in intramolecular C-H insertion reactions was first reported by McKervey and co-workers [53], who used chiral Rh(II) prolinate 17a (Eq. 5.24). Although enantiocontrol was low, this report established the feasibility of the methodology and left open advances that were subsequently made by Ikegami and Hashimoto, who were able to convert a-diazo-p-ketoester 47 into cyclopentanone 48 with 18a (Eq. 5.25) with 32-76% ee, dependent on the substituent Z and the size of the ester alkyl group [54,116],... 

Vizvardi, K., Desmet, K., Luyten, I., Sandra, P., Hoornaert, G., and Van der Eycken, E. (2001) Asymmetric induction in intramolecular meta photocydoaddi-tion cyclodextrin-mediated solid-phase photochemistry of various phenoxy-alkenes. Organic Letters, 3 (8), 1173—1175. 

A high asymmetric induction in intramolecular hetero Diels-Alder reactions was found using chiral 1-oxa-1,3-butadienes with a stereogenic center in the tether [54]. Such compounds can easily be obtained by a Knoevenagel condensation of a 1,3-dicarbonyl compound such as iV,N-dimethylbarbituric acid with a chiral aldehyde bearing a dienophile moiety [169 a] (Scheme 2-3). With the stereogenic center in a-position relative to the oxadiene or dienophile moiety an excellent induced diastereoselectivity is obtained for the nearly exclusively formed trans-cycloadduct (simple diastereoselectivity = 97.9 2.1 and 98.3 1.7,... 

Molander, G. A., Etter, J. B. Lanthanides in organic synthesis. 8. 1.3-Asymmetric induction in intramolecular Reformatskii-type reactions promoted by samarium diiodide. J. Am. Chem. Soc. 1987, 109, 6556-6558. 

Asymmetric induction in intramolecular cyclopropanation reactions can be achieved by substrate and catalyst control. In the example of 24, a stereogenic center in the tether of the unsaturated diazocarbonyl compound controls the diastereofacial selectivity of the cyclopropanation reaction. In the examples of and 27, the diastereoselectivity of the cycli-zation process is controlled by the siloxy group at the stereogenic center obviously, this group prefers the exo position in the transition state. However, the catalyst is also important, since practically no diastereoselectivity for 26 resulted when bis(Al-tc/-t-butylsalicylaldimato)cop-per(II) was used. 

Scheme 6.38. (a) Enantioselectivity in intramolecular cyclopropanations [140,141]. (b) Double asymmetric induction in intramolecular cyclopropanations [142]. (c) Group-selective asymmetric cyclopropanation [142]. 

The enormous potential of the intramolecular Heck reactions has been demonstrated impressively in elegant syntheses of even the most complicated natural product skeletons. The intramolecular Heck reaction on the achiral iodoalkenes 354 and the corresponding alkenyl triflates 357 with their pairs of enantiotopic double bonds in the cyclohexa-1,4-diene moieties, applying catalysts with chiral ligands, gave tetrahydronaphthalenes 359 or hydrindanes from precursors such as 354, 357 or corresponding precursors with one less carbon in the tether [204f], with excellent enantioselectivities. Complementary to the asymmetrically induced inter-molecular arylation with triflates (Scheme 8.72), reasonable asymmetric inductions in intramolecular reactions were also achieved with iodides on the addition of silver salts to promote the formation of cationic intermediates such as 356 (Scheme 8.73)... 

Scheme 5 Asymmetric induction in intramolecular allylboration reactions...

K., Asymmetric induction in intramolecular [5+2] cycloaddition of 2-(4-aIkenyl)-5-benzoyloxy (or 5-silyloxy)-4-pyrones involving migration of the pyrone 0-5 group to 0-4, Heterocycles, 45, 2097, 1997. 

In contrast to the intramolecular carbenoid C-H insertion, the inter-molecular version has not been greatly developed and has been for a long time regarded as a rather inefficient and unselective process. In this context, Davies and Hansen have developed asymmetric intermolecular carbenoid C H insertions catalysed by rhodium(II) (5 )-A-(p-dodecylphenyl)sulfonylprolinate. " Therefore, these catalysts were found to induce asymmetric induction in the decomposition of aryldiazoacetates performed in the presence of cycloalkanes,... 

Overman s group [71,72] enlisted an intramolecular Heck reaction to form a quaternary center in their efforts toward ( )-gelsemine. When the cyclization precursor 70 was submitted to the ligandless conditions [Pd2(dba)3, Et3N] in the weakly coordinating solvent toluene, the quaternary center was formed as a 9 1 ratio of diastereomers (72 71 = 89 11). Addition of a silver salt in polar solvent THF completely reversed the sense of asymmetric induction in the cyclization reaction (72 71 = 3 97). 

In 1974 the first example of asymmetric induction in an intramolecular Pummerer reaction was observed and reported. Stridsberg and AUenmark (300) treated optically pure o-benzylsulfinylbenzoic acid 271 with acetic anhydride in the presence of dicyclohexyl-carbodiimide (DCC) and found that the Pummerer reaction product, 3,l-benzoxathian-4-one 272, was optically active. The sign and optical rotation values ([alp varied from +42° to -11°) of 272... 

Scheme 4 Asymmetric induction in an intramolecular [2+2] photocycloaddition reaction using optically pure coordinatoclathrate host 9b...

M. Hirama u. S. Ito, Heterocycles 28, 1229-1247 (1989) . .Asymmetric Induction in the Intramolecular Conjugate Addition of y- or d-Carbamoyloxy-a,/ -unsaturated Esters. A New Method for Diastcreo-selective Amination and Divergent Syntheses of 3-Amino-2,3,6-trideoxyhcxoscs". 

An alternative approach in the asymmetric catalysis in 1,3-dipole cycloaddition has been developed by Suga and coworkers. The achiral 1,3-dipole 106 was generated by intramolecular reaction of an Rh(ii) carbene complex with an ester carbonyl oxygen in the Rh2(OAc)4-catalyzed diazo decomposition of <9-methoxycarbonyl-o -diazoacetophenone 105 (Scheme 12). The asymmetric induction in the subsequent cycloaddition to G=G and G=N bond was achieved by chiral Lewis acid Sc(iii)-Pybox-/-Pr or Yb(iii)-Pybox-Ph, which can activate the dipolarophile through complexation. With this approach, up to 95% ee for G=0 bond addition and 96% ee for G=G bond addition have been obtained, respectively. ... 

Some aspects of the chemistry of helicenes require still more attention. Since the interpretation of the mass spectrum of hexahelicene by Dougherty 159) no further systematic work has been done on the mass spectroscopy of helicenes, to verify the concept of an intramolecular Diels-Alder reaction in the molecular ion. Though the optical rotation of a number of helicenes is known and the regular increase of the optical rotation with increasing number of benzene rings has been shown, the dependence of the rotation on the helicity is still unknown. The asymmetric induction in the synthesis of helicenes by chiral solvents, or in liquid crystals, though small, deserves still more attention because application to other organic compounds will be promoted when the explanation of observed effects is more improved. 

Asymmetric ethylidene transfer has been achieved in the reactions of 1-cyclohexenyl ethers carrying a chiral auxiliary with 1,1-diodoethane/diethylzinc 39. Asymmetric induction in the reaction of diazofluorene with fumaric esters bearing chiral alcohol moieties has been investigated (equation 84)140,141. Kinetics of intramolecular cyclopropanation in... 

One of the first examples of high asymmetric induction in the intramolecular [2 + 2] photocycloaddition in which the chiral center located at the side chain found in Winkler and coworkers113 approach to the synthesis of (—)-histrionicotoxin alkaloid 240. Irradiation of 237 is the key step in the synthetic strategy. The isomer 238 was formed in... 

Photochemical (4 + 2) cycloaddition of anthracene and dimethyl fumarate or maleate have been reported by Kaupp [301], The reaction requires a high concentration of dimethyl fumarate or maleate owing to the short lifetime of the excited singlet state of anthracene and its facile dimerization. However, irradiation of a benzene solution of (9-anthryl)methyl methyl fumarate or maleate resulted in the intramolecular (4 + 2) photocycloaddition efficiently [302], Asymmetric induction in this intramolecular photocycloaddition of 291b-c was also investigated (Scheme 83). 

The sense of asymmetric induction in the a-oxygenated aldehydes, which shows a strong kinetic preference for the formation of the syn diol, is consistent with the classic Gram model as in 27 (Scheme 32). Once the complexation occurs, the allyl group is transferred to the carbonyl carbon from the less hindered 7r-face opposite to that occupied by the R group. In 28, the chelation pathway is able to adopt a chair conformation which accommodates the favored formation of the syn-diol. For /3-chelate reactions, the factors which influence the product formation appear to be the same. When 29 forms, the intramolecular attack occurs syn to the hydroxyl group. This reaction trajectory leads preferentially to the anti-dio, provided that a chairlike transition states such as 30 is followed. 

The above level of diastereoselectivity is noteworthy because the protected form (alkylether) of 159 fails to show 1,3 asymmetric induction in the reaction with organometallics such as cuprates 104a). As in other cases of 1,3 asymmetric induction 75a), the results are not easy to rationalize. It is likely that the reactions are initiated by deprotonation of the hydroxyl group. An intramolecular transfer of the... 

Eycken and coworkers [121] employed ji-CDx as a chiral template for asymmetric induction in the intramolecular meta-photocycloaddition [126,127] of 4-phenoxy-1-butenes 48 and 50 in the solid state. (Scheme 19.)... 

Since the concept of topochemically controlled reactions was established, various approaches to asymmetric synthesis using a solid-state reaction have been attempted, most actively by the research group at the Weismann Institute. Their studies have been concerned with the bimolecular reactions of chiral crystals in the solid state. In these studies, successful absolute asymmetric synthesis has been performed by using topochemically controlled four-centered photocyclodimerizations of a series of unsymmetrically substituted diolefin crystals. Research on reactivity in the crystalline state has been extended in recent years to a variety of new systems, and many absolute asymmetric syntheses have been provided. Successful examples of absolute asymmetric synthesis using chiral crystals are listed in Tables 2 to 4, which are divided into three categories intermolecular photoreaction in the solid state (Table 2), intramolecular photoreaction in the solid state (Table 3, A-D), and asymmetric induction in the solid-gas and homogeneous reactions (Table 4). 

---