Cycloisomerization BINAP

Zhang s group has reported highly enantioselective cycloisomerization processes catalyzed by rhodium(i) chiral complexes (Scheme 53). For instance, (A)-BINAP gives excellent asymmetric induction in the reaction of enediyne 212 to furnish the quasi-enantiopure Alder-ene product 213.219... 

When (R,R)-Me-Duphos, (R,R,R,R)-BICPO [9] or BINAP [10] is used, the rhodium-catalyzed asymmetric cycloisomerization of 3 affords 4 with up to >99.5% enantiomeric excess (Scheme 7 2). This methodology was applied to the synthesis of functionalized a-methylene-y-butyrolactone derivatives 6 such as (-i-)-pilocarpine 7 (Scheme 7.3) [11]. 

Silver salts or reagents have received much attention in preparative organic chemistry because they are useful catalysts for various transformations involving C-G and C-heteroatom bond formation.309 Especially, the silver(i)/ BINAP (2,2 -bis(diphenylphosphino)-l,T-binaphthalene) system is a very effective catalyst for a variety of enantio-selective reactions, including aldol, nitroso aldol, allylation, Mannich, and ene reactions. Moreover, silver salts are known to efficiently catalyze cycloisomerization and cycloaddition reactions of various unsaturated substrates. Recently, new directions in silver catalysis were opened by the development of unique silver complexes that catalyze aza-Diels-Alder reactions, as well as carbene insertions into C-H bonds. 

Cycloisomerization. Gold salts and complexes are popular catalysts for organic transformations because it is found that the metal has high affinity to allenes and alkynes. A gold ion usually requires stabilization of a phosphine. As shown by the cyclization of 1,2,7-aIkatrienes, BINAP and its congners are adequate ligands. 

BINAP were used, the Rh-catalyzed asymmetric cycloisomerization... 

Microwave irradiation promotes a domino Sonogashira coupUng/5-exo-dig cycloisomerization reaction of substituted 2-halobenzamides 49 with phenylacety-lene 50 to give 3-(phenylmethylene) isoindoUn-l-ones 51 in 42-94% yields. The best result was observed with the aid of DBU and PdCl2(MeCN)2/BINAP (2,2 -Bis(diphenylphosphino)-l,l -binaphthalene) in DMF at 120°C for 30min (Scheme 12.19). Microwave irradiation not only accelerated the reaction rate but also increased the yield of the products. This domino method has been extended to different substrates of amidines and sulfonamides [40]. 

Moreover, deconstructing the tridentate architecture of the triphos ligand into chiral diphosphines such as xyl-BINAP or SEGPHOS provided an enantios-elective cycloisomerization with enantio-ratios up to 98 2 (Scheme 31) (68). 

The Rh-BINAP-catalyzed intramolecular Alder-ene cycloisomerization is very rapid and, therefore, sequentially Rh-catalyzed sequences for the efficient enantioselective generation of five-membered carbo- and heterocycles were envisioned. Korber et al. [21] reported the enantioselective rhodium-catalyzed cycloisomerization of alkyl and (hetero)aryl alkynyl allyl alcohols for the generation of aldehyde-bearing chiral 4-alkyl 3-alkylidene THFs and tetrahydro-furanones, which were converted into a,P-unsaturated carbonyl side chains in a one-pot manner via a concluding Wittig olefination in good yields. 

Based on the initial Alder-ene cycloisomerization of alkyl and (hetero)aryl-substituted alkynyl allyl alcohols 13, the rhodium(I)-BINAP complex subsequently can be employed in the reduction of the primary products with hydrogen, furnishing 2,7-dioxabicyclo[3.2.1]octanes 14 in the sense of a sequentially Rh-catalyzed one-pot process (Scheme 12.7) [22]. 

Scheme 12.7 Enantioselective sequentially Rh(l)-BINAP-catalyzed cycloisomerization-hydrogenation-isomerization-acetalization sequence.

Okamoto et al. [31] reported an enantioselective Rh-BINAP-catalyzed allyl ether isomerization-cycloisomerization domino sequence of phenol- or naphthol-linked 1,7-enynes 17 to give dihydrobenzofurans and dihydronaphtho-furans 18 (Scheme 12.9). 

Fig. 10.9 Synthesis of quinolines via Pd-BINAP promoted ene-type cycloisomerizations [10]...

Fig. 10.17 Rh-BINAP promoted Alder-ene cycloisomerization of a sulfonamide tethered enyne [30]...

The sense of chiral induction from the Rh-BINAP catalyst was determined by anomalous X-ray crystal diffraction on the 3-benzyhdenepyrroIidine obtained by cycloisomerization of a Af-2-pentenyl-N-(3-phenyl-2-propynyl)sulfonamide (Fig. 10.17). The results showed that the (R)-BINAP rhodium complex induces an (R)-config-uration on the newly formed stereogenic center [30]. 

In later work, Zhang also examined the reactivity of ether substrates with additional substituents at the allylic position (Fig. 10.19) [32] and demonstrated that an highly effective kinetic resolution process takes place in the presence of rhodium/BINAP catalysts. In these cycloisomerization processes, the initial kinetic resolution coupled with a diastereoselective cyclization step allow the synthesis of tetrahydrofurans with two adjacent stereogenic centres, with excellent e.e. and conversion rates. In the representative reaction shown in Fig. 10.19, the 5-configured BINAP matches the 2/ -configured enyne substrate which is thus quantitatively converted into the expected tetrahydrofurane. The 25 -configured substrate remains unchanged. 

Fig. 10.20 Enantioselective synthesis of lactames and y-lactones via Rh-BINAP promoted cycloisomerization [27, 34]...

Excellent enantiomeric excesses have been obtained by Zhang et al. also in the synthesis of cyclopentanes and cyclopentanones via cycloisomerization of carbon-tethered enynes promoted by the same cationic Rh/BINAP catalysts (Fig. 10.23) [35]. These stmctures had been targeted most particularly since they are useful building blocks for the construction of biologically active molecules and industrially relevant compounds such as prostaglandins and jasmonates. Actually, enantiomerically pure (i5,25)-dihydrojasmonate could be prepared indeed by this elegant methodology. 

Shibata also reported on the enantioselective cycloisomerization of nitrogen-bridged 1,6-enynes into 3-azabicyclo[4.1.0.]heptenes. In this reaction, Tol-BINAP proved to be the best catalyst, although only moderate enantioselectivity levels could be attained [59](Fig. 10.48). 

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