Aryl alkyl carbinols

With 1-2 mol% of 64b, racemic mixtures of aryl-alkyl carbinols 86 [103], propargylic [104] and allylic alcohol [105] 88 and 87, respectively, were resolved (Fig. 43). The best selectivities were attained for aryl-alkyl-carbinols 86, where the unreacted isomer was obtained with excellent ees after 55% conversion, while propargyl alcohols 88 required clearly higher conversions for high ees in the remaining starting material [106]. 

Benzyl alcohols Aryl alkyl carbinols (11) can be oxidized to ketones (12) by the direct electrochemical method (Eq. 4) since they possess their oxidation potentials at around 2.0 V versus SCE (saturated calomel electrode) however, cleavage products decrease the selectivity [14]. 

After further optimization of catalyst structure, phosphine catalyst 2 was found to be very effective in the kinetic resolution of aryl alkyl carbinols (fcrei=31-369, Scheme 3) [12]. Reactions exhibit high selectivity factors when... 

An interesting approach to translating remote chirality into enantiomer discrimination relies upon blocking one face of the heterocycle using axially chiral DMAP analogs. To this end, Spivey and co-workers have examined catalysts 39 and 40, obtained in optically pure form by preparative HPLC [38]. Catalyst 39 is effective for the kinetic resolution of aryl alkyl carbinols with good selec-tivities (krei=8.4-27, see Scheme 7). The substitution on the 4-position nitrogen... 

Significantly higher selectivity was reported for the first time in 1996 by Vedejs et al. using either the C2-symmetric phosphines 1-4 [6, 8] (Scheme 12.1) or the bicyclic systems 5 (Scheme 12.2) [7, 8]. For example, selectivity factors in the range 12-15 were observed when phosphine 2a was used in the acylation of aryl alkyl carbinols with 3-chlorobenzoic anhydride (Scheme 12.1). 

Quite efficient nucleophilic catalysts with planar (21a-c) and axial (22a-d) chirality were recently developed by Fu et al. [17-22] and Spivey et al. [23-25], The ferrocene-derived catalysts developed by Fu (21a-c) were first tested in the kinetic resolution of aryl alkyl carbinols with diketene as the acyl donor. 

Besides the preparation of aryl alkyl carbinol, many other secondary alcohols have been prepared in good to excellent optical purity through the use of this method, although improvements... 

Beside the preparation of aryl alkyl carbinol, many other secondary alcohols have been prepared in good to excellent optical purity through the use of this method, although improvements of the catalytic system have to be found to obtain good results with all types of ketones, especially dialkyl ketones. Numerous complex target molecules have been prepared where the asymmetric reduction is a key step. The Corey reduction is now a standard reaction for laboratory-scale preparation. 

GottareUi G, Samori B, Stremmenos C, Torre G. 1981. Induction of cholesteric mesophases in nematic liquid crystals by some chiral aryl alkyl carbinols. A quantitative investiga tion. Tetrahedron 37(2) 395 399. 

Table 1. Dependence of the twisting power of the chiral aryl-alkyl carbinols on R and R substituents and handedness of the cholesteric induced helices.

Seebach and Daum (75) investigated the properties of a chiral acyclic diol, 1,4-bis(dimethylamino)-(2S,35)- and (2K,3/ )-butane-2,3-diol (52) as a chiral auxiliary reagent for complexing with LAH. The diol is readily available from diethyl tartrate by conversion to the dimethylamide and reduction with LAH. The diol 52 could be converted to a 1 1 complex (53) with LAH (eq. [18]), which was used for the reduction of aldehydes and ketones in optical yields up to 75%. Since both enantiomers of 53 are available, dextro- or levorotatory products may be prepared. The chiral diol is readily recoverable without loss of optical activity. The (- )-52-LAH complex reduced dialkyl and aryl alkyl ketones to products enriched in the (S)-carbinol, whereas (+ )-52-LAH gives the opposite result. The highest optical yield of 75% was obtained in the reduction of 2,4,6-... 

Reduction of aryl alkyl ketones with 78 was quantitative and (- )-/V-meth-ylephedrine was recovered with no loss in rotatory power. High optical yields were obtained with linear aliphatic chains in the ketone, but branching a to the carbonyl group lowered the optical yields significantly. Reduction of aliphatic methyl ketones with 78 at 0°C gave (S)-carbinols in low optical yield (14 to 46%). 

The transformation of lithio derivatives of dibenzothiophene into alkyl, alkenyl, hydroxyalkyl, formyl, acetyl, carboxylic acid, alkyl and arylsilyl, boronic acid, aryl and carbinol derivatives of dibenzothiophene is dealt with in the appropriate sections. In addition, the four mono-tritio derivatives of dibenzothiophene have been prepared from the corresponding lithio derivatives via hydrolysis with tritiated water (Section III, 0,2). ... 

When borohydride reductions are carried out in the presence of either a chiral phase transfer catalyst or a chiral crown ether, asymmetric reduction of ketones occurs but optical yields are low. In the reduction of acetophenone with NaBH4 aided with a phase transfer catalyst (57), 10% ee was obtained. Similarly, reduction of acetophenone with NaBH4 in the presence of the chiral crown ether (58) was ineffective (6% ee)J Sodium borohydride reduction of aryl alkyl ketones in the presence of a protein, bovine semm albumin, in 0.01 M borax buffer at pH 9.2 affords (R)-carbinols in maximum 78% cc. ... 

Lithium borohydride decomposed by /V-benzoylcysteine (61) or /V/v -dibenzoylcystine (62), a sulfur-containing modifier, is a highly efficient chiral reducing agent. A complex prepared from (61), t-butyl alcohol and LiBH4 affords carbinols in maximum 92% ee by the reduction of aryl alkyl ketones in THF at -78 °C (Scheme 13). A LiBH4 complex with (62) and t-butyl alcohol is useful for the reduction of -keto esters to give (R)-P-hydroxy esters in up to 91 % ee. In both cases the use of r-butyl alcohol is essential in order to achieve efficient enantiofacial differentiation. ... 

Itsuno s amino alcohol (70), prepared from L-valine, is an extremely efficient auxiliary for enantioselective reduction of aryl alkyl ketones using BH3. The corresponding alcohols are obtained in up to 100% ee using BH3 and 0.5 equiv. of (70) in THF at 30 °C. Reduction of dialkyl ketones affords (R)-carbinols in 55-73% ee. Halomethyl t-butyl ketones are also converted to the corresponding (5)-carbinols in high optical purity (Scheme 15). Immobilized amino alcohol (70) permits reduction in a continuous flow system. 1-Phenylpentanol of 90% ee was prepared by this catalytic process in almost 1000% chemical yield based on the quantity of chiral auxiliary used. ... 

A limiting factor in the use of these CSPs is the fact that the formation of the solute/CSP complex is dependent on the existence of complimentary interaction sites on the solute. However, this is not a problem with a wide variety of enantiomeric compounds. Type I CSPs have been used to stereochemically resolve alkyl carbinols, aryl-substituted hydantoins, lactams, succinimides, phthalides, sulfoxides, and sulfides (20). 

All other cross-couplings involving terminal alkynes and halo amides have involved ring closure on nitrogen. Thus, o-halobenzamides react with simple terminal alkynes in the presence of a Pd/Cu catalyst to afford either (Z)-3-aryl(alkyl)idene isoindolin-l-ones or the corresponding 2-(l-alkynyl)benza-mides, which are readily cyclized by NaOEt/EtOH or Pd(OAc)2 catalyst to give isoindolin-l-ones (Eq. 11) [35,36]. When acetylenic aryl carbinols are employed as the alkynes, 3-(acylmethyl)isoindolin-l-ones are obtained instead (Eq.l2) [37]. 

Full details have been published of the reduction of aryl alkyl ketones with a chiral hydride reagent prepared from the diamine (23), available from (5)-proline, and L1A1H4 (Scheme 10). Enantiomeric excesses of (S)-carbinols in the range 50—92% are reported. The related chiral pyrrolidine ligand (24) has been... 

Reaction with Phenols and Other Oxygen Nucleophiles. When alcohols react with phenols, DEAD, and TPP, the corresponding aryl alkyl ethers are produced. A tertiary amine may facilitate the reaction. In general, the reaction proceeds with clean inversion of chiral secondary carbinol centers (eq 2 AH = a phenol). Depending on the structure of the substrate, al-lylic rearrangement and neighboring group participation can... 

Scheme 13 Spivey s axially-chiral analog of 4-DMAP in the KR of an alkyl aryl carbinol. [117-127]...

Despite this disappointing result, aryl Grignard additions were attempted on C-3-alkylated 4-keto-L-proline derivative 53. Using THF as solvent, a disappointing 30% yield of the corresponding tertiary carbinol 64 was obtained on treatment with 4 equiv of phenylmagnesium bromide (Scheme 27). 

Aryllithium or alkyllithium treatment gives the corresponding tertiary carbinols, which may be converted to 1-aryl and 1-alkyl analogs by standard... 

---