1- PHENYL-l-PENTANOL

PHENYL-l-PENTANOL, 61, 42 (+)-(/ )-l-PHENYI -1-PENTANOL, 61, 42 (S)-1-PHENYL-l-PENTANOL, 61, 42 N-Phenylpyrrolidinone, 60, 68 Phosphoramidic dichloride, dimethyl- [677-... 

Mazaleyrat and Cram achieved 95% optical purity of (-i-)-(l )-l-phenyl-l-pentanol using the (J ,J )-binaphthylamine 5 with -BuLi and PhCHO at a reagent ratio of 5.0 4.4 1.2 at -120°C in diethyl ether [35]. For a ratio of 3.6 3.4 1.2 they observed only 59% optical purity of the formed (1 )-1-phenyl-1-pentanol. 

Eleveld and Hogeveen employed the benzylamine 6 (respectively its N-lithi-ated derivative) with n-BuLi and PhCHO in a ratio of 4.0 2.7 1.0. The (-)-(S)-l-phenyl-l-pentanol product was obtained in 90% optical purity using a 1 1 mixture of dimethyoxymethane and dimethyl ether at -120°C [36]. Toluene as solvent decreased the optical purity of the product drastically to 18%. However, reinvestigations of this experiment with chiral gas chromatographic analyses rather than optical rotation analyses gave only 72% ee [37]. 

Colombo et al. tested the hydroxypyrroHdine 8 as well as its 0-methylated derivative with -BuLi and PhCHO in a ratio of 3 2 1 [39]. In analogy to Mukaiyama s results, protic 8 gave in dimethoxymethane a higher optical purity [36% of (k)-l-phenyl-1-pentanol] than its aprotic dimethyl ether derivative in hexane [15% of (S)-l-phenyl-l-pentanol]. Salt impurities (e.g.,Lil, LiC104) were foimd to decrease the enantioselectivities. 

Jackman s group performed enantioselective additions of RLi (R=Me, n-Bu) to PhCHO, mediated by a series of chiral Hthium alkoxides [42]. The highest enantioselectivities were achieved with the Hthiated ephedrine derivative lR,2S)-9 with n-BuLi and PhCHO in a ratio of 0.3 0.15 0.1 with 75% ee (GC) of (S)-l-phenyl-l-pentanol in THF at -78°C. An analysis during the course of addition showed that no enantioselective autoinduction [40] by the chiral prod-... 

Knollmiiller et al. tested seven camphor-derived 1,4-amino alcohols according to Eq. (1) and achieved with 12 up to 32% ee of (l )-l-phenyl-l-pentanol (5.2 9.2 1 ratio, in Et20 at -78°C) [47].Diethyl ether was found to give for all ligands superior enantioselectivities than THF. 

Aspinall et al. employed lithium lanthanide binaphtholates 13 (Scheme 2, THF molecules are omitted) in -BuLi additions to PhCHO (1 2 1 ratio) with 67% ee [(S)-l-phenyl-l-pentanol, diethyl ether, -98°C] [48]. With less equivalents of n-BuLi (1 1 1 ratio) only a 39% ee was observed under the same conditions. 

Hilmersson and Davidsson studied by means of intensive NMR investigations a mixed 1 1 complex of n-BuLi and the Hthiated methoxyamine 6 (Scheme 1) in diethyl ether at -80°C [68]. A fluxional exchange between tetrameric and dimeric structures of the chiral Hthiated pyrrolidine 14 and -BuLi is apparent in diethyl ether solution [69]. With the Hthiated amine 15, a derivative of 6,75% ee of (S)-l-phenyl-l-pentanol was obtained in n-BuLi additions to PhCHO, using a ratio of 1.0 0.45 0.25 in diethyl ether at -116°C [37]. The N-methyl derivative gave only 2% ee, while the N-isopropyl derivative 16 yielded 82% ee under the same conditions. This demonstrates Ae crucial role of the N-isopropyl substituent in 16. Addition of dimethoxymethane increased the enantioselectivity of 16 to 91% ee of (S)-l-phenyl-l-pentanol. With Hthiated 16, enantioselectivities of up to 98.5% ee were achieved in butylations of aHphatic aldehydes [70]. Hilmersson demonstrated that the mixed Hthium amide/ -BuLi aggregate alkylates aldehydes faster than the pure -BuLi oHgomers, Eq. (2) [71]. 

Fig. 4 Concentration profiles of 5-phenyl-l-pentanol obtained on Whatman No. 1 chromatography paper at ambient temperature with n-octane as mobile phase. Concentrations of the analyte solutions in 2-propanol were (a) 0.25, (b) 0.50, (c) 0.75, and (d) 1.0 M. The volumes of sample applied were 5 p,l.

STRATEGY AND ANSWER We find that the longest carbon chain (in red at right) has five carbons and it bears a hydroxyl group on the first carbon. So we name this part of the molecule as a 1-pentanol. There is a phenyl gronp on carbon-1 and a methyl gronp on carbon-3, so the fuU name is 3-methyl-l-phenyl-l-pentanol. 

Certain primary alcohols that possess a 5-hydrogen undergo an intramolecular cycliza-tion into a tetrahydrofuran derivative via alkoxy 5-hydrogen abstraction and subsequent ring closure. For instance, w-pentanol reacts with ammonium hexanitratocerate(IV) to afford 2-methylhydrofuran (scheme 15) (Trahanovsky et al., 1969a). This reaction has been further investigated by Doyle and coworkers (Doyle et al., 1975), who were also able to oxidize 5-phenyl-l-pentanol and 4-phenyl-1-butanol into 2-benzyltetrahydrofuran and 2-phenyltetrahydrofuran, respectively. 

L. Colombo et al.110) synthesized two related (S)-proline derivatives and used them as chiral ligands for lithium in reactions of n-butyllithium with benzaldehyde. 1-Phenyl-1-pentanol was obtained with moderate optical purity (4-33% e.e.). Both nitrogen atoms as well as the free hydroxy group in ligands (91) to (94) appear to be essential centers for coordination with the alkali metal. 

Phenylpiperidine has been prepared by warming aniline with 1,5-dibromopentane 4,8 heating 5-anilino-l-bromopentane 6 the dehydration of 5-anilino-l-pentanol over alumina 7 the electrolytic reduction of N-phenylglutarimide 8 the catalytic hydrogenation of l-phenyl-3-hydroxypyridinium chloride 9 the action of bromobenzene on piperidine in the presence of lithium 10 the reaction of fluorobenzene, 1-methylpiperidine, and phenyl-lithium 11 the action of diphenylsulfone on piperidine in the presence of sodamide 12 the diazotization and deamination of l-(2-aminophenyl)piperidine 13 and of l-(4-aminophenyl)piperidine 14 and the present method.18... 

L. M., Smith, P. J., and Baker, M. A., Comparison of antimicrobial activity of nuclear substituted aromatic asters of 5-dimethy-lamino-l-phenyl-3-pentanol and, 3-dimcthy-lamino-1-phenyl-1-propanol with related cyclic analogs, J. Pharm. Sci., 65, 38, 1976. 

Amino-4-methyl-1 -pentanol (l-( + )-Leucinol) [77-(77,77)]-2-Amino-l-[4-(methylthio)phenyl]-l,3-propanediol [5-(77,77)]-2-Amino-l-[4-(methylthio)phenyl]-l,3-propanediol (77)-(—)-2-Amino-2-phenylbutyric acid... 

The 1 -phenyl-pentanol-d) may be prepared in any convenient manner. Benzaidehyde may be reacted with n-butyl-magnesium bromide, and after purification l-phenyl-pentanol-(l) is obtained in the form of a colorless oil at room temperature. 

In 1969, Seebach et al. employed mixtures of -pentane and the tartrate derivative l,4-bis(dimethylamino)-2,3-dimethoxybutane (2) as a chiral co-solvent in -BuLi additions to PhCHO [25]. They obtained 1-phenyl-1 -pentanol in up to 33 % optical purity at -130°C and achieved higher enantioselectivities than with hexane/sparteine or hexane/2,3-dimethoxybutane mixtures under similar conditions. After further systematic studies [26-28], Seebach et al. showed that two equivalents of the polydentate amino ether ligand 3 yield an optical purity of 52% (-78°C,pentane) while a 1 1 ratio gives only 38% ee [29]. 

Piperidines. A soln. of 5-phenyl-5-oxovaleric acid methylamide in benzene added with effective stirring to a soln. of ca. 300% excess LiAlH4 in ether, and refluxed ca. 6 hrs. l-methylamino-5-phenyl-5-pentanol (Y 82%) neutralized with 1 iV HBr, concentrated, dried by distillation with chloroform, treated with PBrg, and the product isolated the next day l-methyl-2-phenyl-piperidine (Y 80%). F, e. s. R. Luke and M. Cerny, Coll. Czech. Ghem. Commons. 2A, 1287 (1959). 

S)-l-Phenyl-alhanol (-)-(S)-/- Phenyl-propanol ( +)-(S)-4-Methyl-pentanol-(2) ( +)—(S)-1- Cyclohexyl-athanol... 

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