Alcohols 13a Research Articles

An Efficient Stereoselective Synthesis of cis-2,6-Disubstituted Tetrahydropyrans via Gold-Catalyzed Meyer–Schuster Rearrangement/Hydration/oxa-Michael Addition Sequence

An efficient stereoselective synthesis of cis-2,6-disubstituted tetrahydropyrans 14a–c has been achieved via gold-catalyzed Meyer–Schuster rearrangement/hydration/oxa-Michael addition sequence from bis-propargylic alcohols 13a–c. The reaction of 13a proceeds via 2,6-disubstituted tetrahydropyran 14′a as an intermediate.

A Practical Route to Regiospecifically Substituted (R)- and (S)-Oxazolylphenols

New, diversely substituted phenolic oxazolines 14a−d and 15a−d were prepared by two complementary routes A and B, starting from salicylic derivatives 4−7 and various enantiomerically pure 1,2-amino alcohols 13a−d. In route A, the 1,2-amino alcohols 13a−d were directly condensed with the salicylic acids 5 and 7, using the Appel reaction, whereas in route B the amino alcohols 13b−d were treated with the 2-hydroxybenzonitriles 4 and 6, under Witte−Seeliger conditions. The latter route was advantageous for L-valinol 13b and L-tert-leucinol 13c, while route A was the method of choice for the new, sterically demanding amino alcohol 13a, prepared from D- and L-serine. The nitro group in the salicylic derivatives 5 and 6 was introduced by means of a regiospecific ipso substitution of a tert-butyl group by nitric acid. The structure of the nitro product 5 was unambiguously assigned by NOE spectroscopy on the basis of the recently developed DPFGSE-ROE pulse sequence.

Sequential Rearrangements and Unusual Isomerization with KO tBu: Synthesis of anti-12-Vinyltricyclo[6.3.1.0 2,7]dodeca-2,4,6,9-tetraene and its Derivatives

The reaction of alcohol 13a with SOCl 2 gave 13b, 14a and 15a, and the reaction of chloride 13b with AgNO 3 (in MeO −/MeOH) gave 13c, 14b and 15b. In these reactions, 14a, 14b, 15a and 15b are the major products by sequential rearrangements. Treatment of the rearranged products 14a and 15a with KO t Bu (potassium tert-butoxide) gave 18 by an unusual isomerization. Compounds 19, 20 and 21 were also synthesized in different reactions. Compounds 14, 15, 19, 20 and 21 are all derivatives of anti-12-vinyltricyclo[6.3.1.0 2,7]dodeca-2,4,6,9-tetraene 19, and the syntheses of 19, 20 and 21 support the structures of compounds 14, 15 and 18.

Utilization of industrial waste materials. Part 14.† Synthesis of β-amino alcohols and thiols with a 2-azabicyclo[3.3.0]octane backbone and their application in enantioselective catalysis

New, chiral β-tert-amino tert-alcohols have been synthesized from the enantiomerically pure sec-amine (all-R)-1b via the new glycine, alanine and phenylglycine derivatives 2–6. Grignard additions to these esters provided the new rigid amino alcohols 7–11 in fair yields. The absolute configurations of the stereogenic centers, which arose during the alkylation step, were assigned by an independent route leading to some of the optical antipodes of 7–10. Condensation of enantiomerically pure β-amino alcohols 13a–g, 16 and 17 with γ-ketoester rac-12 afforded the N,O-acetals 14a–g, 18 and 19, which were subsequently reduced to the β-tert-amino alcohols 10a,c and 15a–g. X-Ray analysis of compound 19 was performed to verify the stereochemistry observed by chemical correlation. The nucleophilic ring opening of enantiomerically pure styrene oxide by amine 1b resulted in the formation of regioisomeric amino alcohols 9a, 21a, and 10a, 21b. Amino thiol derivatives 22 and 25a,b were prepared by treatment of 10a and 15a,b, respectively, with methanesulfonyl chloride followed by regio- and stereoselective cleavage of the in situ formed aziridinium ions with potassium thioacetate. Reduction of these compounds to thiols 23 and 26a,b and subsequent oxidation afforded amino disulfides 24 and 27a,b. Finally, the bicyclic β-amino alcohols and thiols were used as chiral ligands in the enantioselective addition of diethylzinc to benzaldehyde and ee values up to 96% were found.

Comparison between a Diarylferrocenylmethylium Ion and Its Isolobal Cobalt Species: Similarities and Differences

Reaction of {(1,2,8,9-η)-tricyclo[7.5.0.01,7]tetradeca-1,8-diene}{η5-(methoxycarbonyl)cyclopentadienyl}cobalt (9) with either 2 mol of arylmagnesium bromide or aryllithium and subsequent hydrolysis yields the alcohols {(1,2,8,9-η)tricyclo[7.5.0.01,7]tetradeca-1,8-diene}{η5-(diarylhydroxymethyl)cyclopentadienyl}cobalt (13a−c). The treatment of the yellow colored alcohols 13a−c with HBF4 in ether affords the tetrafluoroborates of the violet colored carbocations 14a−c. Investigations of single crystals of 14b by means of the X-ray technique show a displacement of the C1−Cexo bond by α = 10.8° toward the metal and a pronounced bond alternation in the fulvene moiety. The bending of C1−Cexo is considerably larger than in the corresponding alcohol 13b (α = 2.5°). The interaction between the exo-carbon and the metal in 14b is further substantiated by comparison of the 13C-NMR chemical shift of 14b with 13b (Δδ = −65 ppm). The comparison of the data obtained for 14b with those of diphenylferrocenylcarbenium ion 1b suggests a stronger bonding between metal and fulvene moiety in 1b as compared to 14b. These results are substantiated by the results of ab initio calculations on 1b and 4a which show a smaller positive charge at the exo-carbon in 4a than in 1b and a stronger bond index between the exo-carbon and the metal in 1b as compared to 4a.

Efficient Synthesis of Ephedra Alkaloid Analogues Using an Enantiomerically Pure N-[(R)-(+)-alpha-Methylbenzyl]aziridine-2-carboxaldehyde.

Efficient preparation of enantiomerically pure (2S)-aziridine-2-carboxaldehyde 9 and its 2(R) isomer and highly diastereoselective addition of organolithium reagents to the aldehyde 9 are described. The diastereoselectivity in additions of the lithium reagents seems to come from "chelation-controlled" carbon-carbon bond formation and is influenced by the source of the organometallic compound, solvent, and the presence of a Li salt. The C(3)-N bond of the aziridine ring of the addition products was regioselectively reduced by catalytic hydrogenation in the presence of Pearlman's catalyst to provide enantiomerically pure 1,2-amino alcohols. The absolute stereochemistries of the amino alcohol 13a were assigned as (1S,2S) when the C-1 substituent was phenyl by comparison with those of commercially available norpseudoephedrine.

Asymmetric Synthesis. 39.1 Synthesis of 2-(1-Aminoalkyl)piperidines via 2-Cyano-6-phenyl Oxazolopiperidine

The asymmetric synthesis of a series of 2-(1-aminoalkyl) piperidines using (-)-2-cyano-6-phenyloxazolopiperidine 1 is described. LiAlH(4) reduction of 1 followed by hydrogenolysis led to the diamine 3. The same strategy applied to C-2-methylated compound 7 afforded [(2S)-2-methylpiperidin-2-yl]methanamine (9). Addition of lithium derivatives to the cyano group of 1 resulted in the formation of an intermediate imino bicyclic system (11a-c) which could be diastereoselectively reduced to substituted diamino alcohols 13a-c. The addition of an excess of PhLi to 1 in the presence of LiBr furnished disubstituted amine 19, the precursor of diphenyl[(2S)-piperidin-2-yl]methanamine (22).

Stereoselective synthesis of alcohols, XLI. Chirality transfer to generate quaternary stereogenic centers by an allylboration reaction

AbstractThe acyclic alcohols 13 and 14 having a neighboring quaternary stereogenic center can be obtained in diastereoselectivities of > 95% by addition of the ß,γ,γ‐trisubstituted allylboronates 12 to aldehydes. Starting from the nonracemic allylboronates 19 of presumed 84–92% e.e., we have obtained the alcohols 13a and 14a with the corresponding levels of the e.e.