Naphthols, reaction with unsaturated

By derivatizing an a,p-unsaturated acid into the mono ester of chiral 1,1 -bi-8,8 -naphthol the reaction with lithium dialkylcuprates leads to saturated ketones containing chirality centers at the p-carbon atoms." Consecutive 1,4-addition and 1,2-addition account for this result. The alkyl transfer to enones from Grignard reagents under copper catalysis is subject to chiral modification, e.g., by the introduction of 56" or 57." ... 

In Chapter 6 the use of isoprene (Table 6.1) and of geranyl halides in reactions with naphthol and phenol respectively has been briefly referred to. In early work, isoprene with phenol in toluene containing 71% phosphoric acid, when reacted over 16 hours at ambient temperature (ref. 2) gave 4-(3-methylbut-2-enyl)phenol, the corresponding 2- isomer and 4-(3-methyl-3-hydroxybutyl)phenol in the phenolic products and in the neutral fraction, smaller proportions of 2,2-dimethylchroman and 6-(3-hydroxyisopentyl)-2,2-dimethylchroman. Hydrogenation of the unsaturated phenols afforded the respective 4- and 2-isopentylphenols. 

Another example of organocatalytic AFC alkylation reaction with p,y-unsaturated a-keto esters was reported by Wang and co-workers in 2012. In the presence of 10 mol% rosin-derived tertiary amine-thiourea 96, a variety of p,y-unsaturated a-keto esters reacted with 1-naphthol smoothly to afford the modified chromanes 97 in good yields (79-86%) with up to 96% ee (Scheme 6.39). Again, the hydrogen bonding between substrates and catalyst was proposed to be a key element for the enantioselective control. 

On the other hand, Yang etal. [33] have developed an organocatalyzed enantioselective FC-type addition reaction of 2-naphthol 212 with p,y-unsaturated a-ketoesters 209 using a cinchona alkaloid-derived thiourea catalyst 213 (Scheme 2.30). The resulting product 214 is in rapid equilibrium with the cyclic hemiketal 215, which was dehydrated with a catalytic amount of concentrated H SO in a one-pot fashion, providing the naphthopyran derivatives 216 with moderate to good yields (51-91%) and enantioselectivities (57-90% ee). 

In addition to the carboxylate-like reactivity of carbenes, these complexes also display a rich and quite remarkable metal-based chemistry. This can be divided into two types thermal and photochemical. The principle thermal reaction is the Dotz reaction with alkynes (Scheme 8.15). This involves heating an a,p-unsaturated carbene 8.40 with an alkyne and results in the formation of a phenol 8.41. The phenolic carbon is derived from CO. The a,p-unsaturation may be a part of a benzene ring, in which case a naphthol will be formed. If the reaction is run in the presence of acetic anhydride and a base, the corresponding acetate is... 

Kumaraswamy et al. reported asymmetric 1,4-addition reactions using chiral calcium complexes prepared from calcium chloride and dipotassium salt of BINOL or Hg-BESfOL (5,5, 6,6, 7,7, 8,8 -octahydro-l,l -bi-2-naphthol) [42-45]. After optimization of the calcium salts and reaction conditions, the calcium catalyst was successfully applied to asymmetric 1,4-additions of malonates or p-ketoesters to a,p-unsaturated carbonyl compounds (Tables 4 and 5) [42, 44]. Among the a,p-unsaturated carbonyl compounds employed in the reactions with malonates, cyclopentenone was found to be a suitable substrate, and high enantioselectivities were obtained (Table 4, entries 3 and 4). In the cases of p-ketoesters, 2-oxocyclopentanecarboxylates are suitable for this reaction, and good yields and good enantioselectivities were observed (Table 5, entries 2, 7, and 8). 

The 774-vinylketene complex (85) could be oxidatively decomplexed with Ce(IV) to afford the lactone (87). Although no reaction was observed with methanol (unlike a postulated chromium analogue16,18 26), treatment with sodium methoxide produced the expected /3, y-unsaturated ester (88). Thermolysis of complex 85 afforded no trace of the naphthol that one would expect33 from a proposed chromium vinylketene complex with the same syn relationship between the phenyl group and the ketene moiety. Instead, only the furan (89.a) was seen. Indeed, upon exhaustive reaction of tricarbon-ylcobalt carbenes (84 and 90) with different alkynes, the furans (89.a-d) were isolated as the exclusive products in moderate to excellent yields. 

We have found that the novel chiral self-dimerizahon of V complexes produces an active unsaturated structure with a new chiral conformation on a Si02 surface, and provides highly enanhoselective achve sites for the asymmetric oxidative coupling of 2-naphthol [35, 36]. Table 10.3 summarizes catalyhc activities, selectivities and enantiomeric excess (e.e.) of homogeneous and heterogeneous V catalysts for the oxidative coupling of 2-naphthol. The homogeneous reactions on a representative L-leucine based V monomer did not exhibit the catalyhc activity. Only in the presence of chlorotrimethylsilane as an acidic promoter did the reachon proceed, but conversion was as low as 15% at 293 K, selectivity to BINOL and e.e. to (P)-BINOL were quite low at 73% and 8%, respectively (Table 10.3). Furthermore, loss of activity occurred and no reachon proceeded after 9 days. 

Usually the Knoevenagel condensation yields the unsaturated product, but, with appropriate aldehydes, 3-hydroxymalonates can be isolated. The unusual formation of an a-naphthol (74) has been reported from the reaction of diphenylacetaldehyde (73) with diethyl malonate under Knoevenagel conditions." Condensation of stdicyl dehydes and other aromatic o-hydroxy aldehydes with malonates is still in use for the synthesis of the corresponding coumarin-3-carboxylic esters (75). - " Reduction... 

Cyclobutenones are fairly common side-products in the reaction of chromium arylalkoxy-carbenes with internal alkynes. As indicated in Scheme 5-1, the branch point in the formation of cyclobutenone versus naphthol products is believed to be vinylketene intermediate 4, which may undergo electrocyclic ring closure to 9, followed by reductive elimination to the product [7 a]. Cyclobutenone formation occurs only in the presence of internal or external ligands that can coordinate to unsaturated chromium species sufficiently well to prevent complexation to an internal n-system and thus divert the system toward 9. Depending on the alkyne and aryl substitution patterns and the reaction conditions, cyclobutenone formation can be made to predominate. Thus, solvents of good coordinating ability such as acetonitrile, o-OMe aryl substitution (which allows internal coordination to chromium), and bulky alkynyl substituents all favor cyclobutenone formation [Eq. (23)] [13]. In fact, the effect of solvent alone can be even more dramatic for the reaction partners in Eq. (21), a 0.5 M concentration of the carbene complex in acetonitrile gives instead a 78 % yield of cyclobutenone and only a combined 17 yield of quinone and indene products [9]. 

Scheme 6.39 Rosin-derived tertiary amine-thiourea 96 catalyzed AFC reaction of P,y-unsaturated a-keto esters with 1-naphthol reported hy Wang.

Scheme 6.49 Organocatalytic AFC alkylation/cyclization cascade reaction of 1-naphthols with o,p-unsaturated aldehydes reported by Wang.

In 2012, the Bencivenni group reported an AFC alkylation/acetalization cascade of 1- and 2-naphthols with a,p-unsaturated cyclic ketones via iminium catalysis. In this reaction, they found that a stoichiometric amount of water was necessary to obtain high ee values and 1-naphthols showed a better stereochemical outcome than 2-naphthols. Unexpectedly, encumbered l//-inden-l-ones could be applied in this system, furnishing the desired products in high yields (Scheme 6.51). 

Jorgensen et al. reported on enantioselective electrophilic additions to allylic C-H bonds activated by a chiral base, in a reaction of allylidene cyanoacetates or malononitriles with DBAD, catalysed by (DHQ)2PYR, giving y-aminated products in high yield (up to 90%) and excellent enantioselectivity (up to 99% ee). Ye et al. described y-amination of a,p-unsaturated acyl chlorides with azodicarbojylates, catalysed by O-trimethylsilylquinidine (O-TMS-QD) or O-trimethylsilylquinine (O-TMS-Q) to give dihydropyri-dazinones in up 92% yield, and up to 99% ee. Jorgensen s group also reported on asymmetric Friedel-Crafts amination of 2-naphthols with DBAD, to afford nonbiaryl atropisomers in up to 98% ee. ... 

A few examples of naphtho[c]chromenes arise from the intramolecular cascade hydroarylation—cycloisomerization reaction of l-(3-phenoxy-l-propynyl)-2-(l-propynyl)benzene derivatives, catalyzed by a PtCl2/PtCl4 system (13EJO260). 3-Trifluoromethylated benzo[ chromenes are readily accessible through the one-pot reaction of a,P-unsaturated trifluoromethyl ketones with 2-naphthols carried out in the presence of DBU and concentrated sulfuric acid (13SC2883). 

SCHEME 2.30 Organocatalytic asymmetric FC alkylation/cyclization cascade reaction of 2-naphthols with P,y-unsaturated a-ketoesters. 

Chiral phosphoric acid analogs as catalysts in the F-C alkylation reaction of indoles with a,(l-unsaturated aromatic enones were also devised [53]. p,y-Unsaturated a-ketoesters were also used as electrophiles in organocatalyzed F-C alkylations of indoles and 2-naphthols. With indoles, chiral acidic N-triflylphos-phoramide was successfully employed (Scheme 35.4) [28], whereas in the presence of 2-naphthols a thiourea-based catalyst showed better capacity to mediate a sequential F-C/cycUzation process, giving naphthopyran scaffolds in moderate yields and selectivities (up to 90% ee) [54]. Recently, a,P-unsaturated acyl phos-phonates were effectively used as hydrogen bond acceptors for F-C alkylations of indole derivatives in the presence of thiourea catalyst ent-19 [55]. 

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