Asymmetric Benzoylation

In addition, Oriyama was the first to provide a practical protocol for the ASD of mei( -l,2-diols [179-182], Thus, employing just 0.5 mol% of (5)-proline-derived chiral diamine 56 in conjunction with benzoyl chloride as the stoichiometric acyl donor in the presence of EtjN, asymmetric benzoylation of a variety of me o-diols could be achieved with good to excellent enantioselectivities (66-96% ee) and 80% yields (Scheme 24) [179-182],... 

Fujimoto has also described an asymmetric benzoylation system that is effective for ASD of cyclic meso-1,3- and 1,4-diols and which employs phosphinite derivative of quinidine 66 as the catalyst (Fig. 15) [224, 225]. 

Diol 241 is very enantioselectively acylated with 1% of Fu s chiral56 version 243 of DM AP 244. The enantiomeric excess is a staggering 99.7% ee. Other, rather less fancy, chiral nucleophilic catalysts57 have been used very effectively including pyrrolidine derivative 247 for the asymmetric benzoylation of 245. 

Racemic sec-alcohols (12.96) undergo acylation with acetic anhydride using the Fu catalyst (12.95) and achieving very good selectivity factors. Copper bis-oxazohne catalysts also provide high selectivities in the asymmetric benzoylation of trans-1,2-diols. ... 

Matsumura Y, Maki T, Murakami S, Onomura O (2003) Copper ion-induced activation and asymmetric benzoylation of 1,2-diols kinetic chiral molecular recognition. J Am Chem Soc 125 2052... 

A rotaxane-based molecular shutde can have chirality regulated by the position of a macrocycle. Movement of the macrocycle between stations is restricted by the introduction of a bulky group. Asymmetric benzoylation of racemic rotaxane, which has two stations and one hydroxy group on the symmetric position of the shaft molecule, catalysed by a chiral nicotinamide derivative gives enantiomericaUy enriched rotaxane with a 67 33 distribution of enantiomers by trapping the macrocycle on one side (Scheme 5.49) [129]. 

Table 28 Chiral calcium phosphate-catalyzed asymmetric benzoylation reactions...

In another example, dendrimers ended by bisoxazoline ligands attached via click reactions were used for copper catalyzed asymmetric benzoylations, starting from two different diols. Dendrimers 8-Gi and 8-G2 afford good yields and enantioselectivities in both cases, whereas the third generation has a detrimental influence on the enantioselectivity. The copper(II)-catalysts could be readily recovered and reused in several cycles (Fig. 9.9) [44]. 

Fig. 9.9 Cu(II) dendritic complexes 8-Gn and their reuse for catalyzed asymmetric benzoylations...

Figure 4.31 Phosphorus dendrimer-immobilized azabis(oxazoline) ligands for asymmetric benzoylations.

Unsyimnetiical rhodainines can be piepaied by the condensations of one mole of a yW-aminophenol with phthahc anhydride to give an o-benzoyl benzoic acid (27) which is then further condensed with a different yW-aminophenol to give the requited product, Rhodamine 3GO (28) (2). A general route to asymmetrical acid xanthenes has been patented (39). 

The triazole 76, which is more accurately portrayed as the nucleophilic carbene structure 76a, acts as a formyl anion equivalent by reaction with alkyl halides and subsequent reductive cleavage to give aldehydes as shown (75TL1889). The benzoin reaction may be considered as resulting in the net addition of a benzoyl anion to a benzaldehyde, and the chiral triazolium salt 77 has been reported to be an efficient asymmetric catalyst for this, giving the products (/ )-ArCH(OH)COAr, in up to 86% e.e. (96HCA1217). In the closely related intramolecular Stetter reaction e.e.s of up to 74% were obtained (96HCA1899). 

These amino acids were initially synthesized by asymmetric aminomethylation of optically pure (R)- and (S)-N-Acyl-4-phenyhnethyl)oxazolidin-2-ones 52 through TiCVenolates (Evans methodology [135]) with (benzoylamino)methylchloride or benzyl N-(methoxymethyl)carbamate [66, 97-99, 104]. Hydrolytic removal of the auxiliary yielded the N-protected (benzoyl or Z) amino acid 54. Deprotection afforded the free amino acid which was converted to the required Boc- or Fmoc-pro-tected derivatives (Scheme 2.7). 

Ojima, 1., Habus, 1., Zhao, M. (1991) Efficient and Practical Asymmetric Synthesis ofthe Taxol C-13 Side Chain, N-Benzoyl-(2R,3S)-3-phenylisoserine, and its Analogues via Chiral 3-Hydroxy-4-aryl-b-lactams Through Chiral Ester Enolate-Imine Cyclocondensation. Journal of Organic Chemistry, 56, 1681-1683. 

A formal enantioselective synthesis of the antibiotic L-azatyrosine was developed. The asymmetric ally lation of hydrazono esters with ally lsilanes in the presence of a catalytic amount of ZnF2-chiral diamines in aqueous media generated (benzoyl)hydrazino-4-pentenoates in high enantioselec-tivity(Eq. 11.46).77... 

A number of optically active 1,1 -binaphthyl compounds, 8168 and 9,169 have been prepared with a view to use them as asymmetric catalysts. Compounds 8 (X = Br and OTf)170,171 and 9 [R3 = Me(OTf)2]169 have been used to resolve diols in their reaction with benzoyl chloride. Tin hydrides based on structure 8 (X2 = MeH,172 Bu H,173 and Me3CCH2H171) have been designed for carrying out enantioselective reductions. 

Mckenzie carried out a number of asymmetric synthesis by reducing the keto groups in several ketoesters in which the ester group contained a chiral group. Thus he synthesized 1-mandelic acid from benzoyl formic acid by the following steps using 1-menthol... 

An application to the asymmetric synthesis of enantiomer-ically pure tram-hexahydroanthracen-9-ones is shown in Scheme 6. It should be possible to carry out a second stereoselective reductive alkylation of the benzoyl group in 22 as was demonstrated in the related hydrofluoren-9-one and... 

A structural requirement for the asymmetric Birch reduction-alkylation is that a substituent must be present at C(2) of the benzoyl moiety to desymmetrize the developing cyclohexa-1,4-diene ring (Scheme 4). However, for certain synthetic applications, it would be desirable to utilize benzoic acid itself. The chemistry of chiral benzamide 12 (X = SiMes) was investigated to provide access to non-racemic 4,4-disubstituted cyclohex-2-en-l-ones 33 (Scheme 8). 9 Alkylation of the enolate obtained from the Birch reduction of 12 (X = SiMes) gave cyclohexa-1,4-dienes 32a-d with diastereoselectivities greater than 100 1 These dienes were efficiently converted in three steps to the chiral cyclohexenones 33a-d. 

Two years after the discovery of the first asymmetric Br0nsted acid-catalyzed Friedel-Crafts alkylation, the You group extended this transformation to the use of indoles as heteroaromatic nucleophiles (Scheme 11). iV-Sulfonylated aldimines 28 are activated with the help of catalytic amounts of BINOL phosphate (5)-3k (10 mol%, R = 1-naphthyl) for the reaction with unprotected indoles 29 to provide 3-indolyl amines 30 in good yields (56-94%) together with excellent enantioselec-tivities (58 to >99% ee) [21], Antilla and coworkers demonstrated that A-benzoyl-protected aldimines can be employed as electrophiles for the addition of iV-benzylated indoles with similar efficiencies [22]. Both protocols tolerate several aryl imines and a variety of substituents at the indole moiety. In addition, one example of the use of an aliphatic imine (56%, 58% ee) was presented. 

Moreover, phosphoric acid (5)-3r (5 mol%, R = SiPhj) bearing a bulky triphe-nylsilyl group turned out to be a suitable catalyst for the asymmetric Friedel-Crafts alkylation of iV-alkyl pyrroles 31 with M-benzoyl-protected aldimines 32 (Scheme 12) [23]. 2-Pyrrolyl amines 33 were obtained in high yields (66-97%) and moderate to high enantioselectivities (42 to >99% ee). 

Two years later, Terada and coworkers described an asymmetric organocatalytic aza-ene-type reaction (Scheme 28) [50], BINOL phosphate (7 )-3m (0.1 mol%, R = 9-anthryl) bearing 9-anthryl substituents mediated the reaction of A-benzoylated aldimines 32 with enecarbamate 76 derived from acetophenone. Subsequent hydrolysis led to the formation of P-amino ketones 77 in good yields (53-97%) and excellent enantioselectivities (92-98% ee). A substrate/catalyst ratio of 1,000 1 has rarely been achieved in asymmetric Brpnsted acid catalysis before. 

Scheme 6.90 Chiral N-benzoyl-protected a-amino acid allyl esters obtained from 64- and 78-catalyzed asymmetric DKR of racemic azlactones derived from racemic natural nonnatural a-amino acids.

Scheme 6.97 Typical products obtained from the 91-catalyzed asymmetric allylation of N-benzoyl-protected aromatic hydrazones. The product configurations were not determined.

Before an asymmetric synthesis appeared of levofloxacin (1, (—)-ofloxacin), (—)- ofloxacin was isolated via optical, enzymatic, and crystallization resolution of the racemic ofloxacin (17) Drugs Future, 1992 Hayakawa et al., 1986, 1991). For instance, tricyclic core 52 was converted to ( + )-3,5-dinitrobenzoyl derivative 54 in 75% yield (Scheme 4.5). The enantiomers were then separated via high-performance liquid chromatography (HPLC) with a SUMIPAX OA-4200 column to deliver optically pure benzoyl esters 55a and 55b (Drugs Future, 1992 Hayakawa et al., 1986, 1991). 

The asymmetric alcoholytic ring opening of 4-substituted-2-phenyl-4,5-dihydro-l,3-oxazin-6-ones proved to be a efficient method for the preparation of enatiomerically pure /3-amino acid derivatives <2005AGE7466>. Treatment of 2,4-diphenyl-4,5-dihydro-l,3-oxazin-6-one 208 in the presence of the bifunctional chiral thiourea catalyst 211 resulted in formation of an enantiomerically enriched mixture of the unchanged oxazinone (iJ)-208 and allyl (4)-3-benzoyl-amino-3-phenylpropanoate 209. The resolved material (iJ)-208 and the product 209 could easily be separated by a selective hydrolytic procedure that converted oxazinone (iJ)-208 quantitatively into the insoluble iV-benzoyl /3-amino acid 210 (Scheme 37). 

The same compounds isolated by Brigl and coworkers,9 who started from 2,3,4,5,6,7-hexa-O-benzoyl-D-gZt/cero-D-gaZacto-heptononitriIe, were obtained from the ammonolysis of 1,2,3,4,6-penta-O-benzoyl-a-D-mannose,19 namely, a mixture of l,l-bis(benzamido)-l-deoxy-D-mannitol (12) and N-benzoyl-D-mannopyranosylamine (13). Likewise, 1,2,3,4-tetra-O-benzoyl-L-rhamnopyranose,10 having the same steric relationship at the asymmetric carbon atoms as the perbenzoate of D-mannose, also afforded an N-benzoyl-L-rhamnopyranosylamine directly. 

The optically active N-aminoindoline (265) has been applied to the asymmetric synthesis of a variety of a-amino acids (70JA2476, 2488). Starting from TV-benzoyl-1,2,3,4-tetrahy-droquinaldine (257), the chloro amide (258) was prepared by von Braun cleavage. Thermolysis converted (258) to the rrans-unsaturated amide (259) which was epoxidized. On base treatment the epoxide (260) underwent intramolecular nucleophilic displacement and amide hydrolysis to afford indoline (261) stereospecifically. Resolution of (261) was accomplished via the brucine salt of the N-o-carboxybenzoyl derivative (262). Alkaline hydrolysis, N-nitrosation and reduction yielded the levorotatory 1-aminoindoline (265). Reaction of... 

The sulfinyl chirality has shown [86] considerable utility in asymmetric synthesis, particularly for carbon-carbon bond formation (see Sections 2.6.2 and 4.2.8). Its use as the chiral source in a NADH mimic has been reported [240]. Reduction of methyl benzoyl formate by enantiopure l-propyl-(S)-3-(p)-tolyl)sulfinyl-l,4-dihydropyridine yielded the (/ )-mandelate with 96% e.e. 

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