Secondary alcohols organometallic reagents

The enantioselective addition of organometallics to aldehydes is a useful approach to optically active secondary alcohols. Diorganozinc reagents add with excellent enantioselectivity to aldehydes in the presence of a chiral catalyst such as 1,2- or 1,3-amino alcohols (see equation 14 and Table 2). In most cases, diethylzinc has been used, but the reaction could be extended to some other dialkylzinc reagents and to divinylzinc. Alkylzinc halides afford secondary alcohols with a substantially lower enantiomeric excess. Many aldehydes are good substrates, "- but the best results are usually obtained with aromatic aldehydes. ... 

Organometallic reagents are better known for their involvement in the alkylations at ring nitrogen atoms in many heterocycles. However, under proper circumstances, they can promote addition to carbonyl groups. Such is the case when 68 is allowed to react with an excess of Me2BuMgLi at 0°C. The secondary alcohol 69 is obtained in fair yield (Equation 28) <20040L1991>. 

Addition of organometallic reagent to aldehyde preparation of secondary alcohols... 

Two principal approaches to the synthesis of an optically pure chiral secondary or tertiary alcohol from the reaction of an organometallic reagent with an aldehyde or ketone respectively are of current interest. In the first approach an alkyllithium or dialkylmagnesium is initially complexed with a chiral reagent which then reacts with the carbonyl compound. In this way two diastereo-isomeric transition states are generated, the more stable of which leads to an enantiometic excess of the optically active alcohol. This approach is similar in principle to the asymmetric reductions discussed in Section 5.4.1 (see also p. 15). Two chiral catalysts may be noted as successful examples, (10) derived... 

The dialkylzinc additions catalyzed by N,N-di-n-alkylnorephedrines (most typically DBNE) are not limited to primary organometallic reagents. Diisopropylzinc (with a secondary alkyl substituent) adds to benzaldehyde in the presence of a catalytic amount of DBNE to afford the corresponding alcohol with high ee (entry 4). The reaction of diisopropylzinc in the presence of other types of catalysts may result in the reduction of aldehydes. 

Chiral Modification of Achiral Organometallic Reagents. The addition of n-Butyllithium or Ethylmagne-sium Bromide to aldehydes or ketones in the presence of (—)-sparteine resulted in the formation of optically active secondary or tertiary alcohols with 20% ee or lower. Optically active acyl sulfoxides (<15% ee) were obtained by acylation of p-Tolylsulfinylmethyllithium. The asymmetric Reformatsky reaction of ethyl bromoacetate with benzaldehyde proceeds with 95% ee, in an exceptional case (eq 1). ... 

Extension of this methodology to the use of chiral acetals such as (72 equation 19) to produce optically active secondary alcohols is found to be less efTicient than the ketal series. Alkyl Grignard reagents in ether (Table 18) provide the best selectivities (up to 90 10), while aryl and alkynyl organometallics show very little diastereofacial differentiation. ... 

The formation of chiral secondary homoallylic alcohols via the enantioselective addition of allylic nucleophiles to aldehydes is an important tool in organic synthesis. An efficient way to achieve this transformation is to use allylic organometallic reagents in the presence of chiral Lewis acid catalysts. The most widely studied catalysts in the area... 

Reaction with oxiranes (epoxides).2 Dimethylcopperlithium and diphenyl-copperlithium1 are more useful than other organometallic reagents for the nucleophilic ring opening of epoxides. Thus dimethylcopperlithium reacts with propylene oxide (equation 1) and 1,2-epoxybutane (equation 2) to give the expected secondary alcohols as the predominant products. 

Sulfur analogs of some of the described hydroxy linkers and resins (Figure 15.2) have been employed to synthesize resin-bound thioesters that can then be cleaved with alcohols, amines and organometallic reagents to furnish esters, amides, ketones, aldehydes and alcohols [50]. Secondary amines react sluggishly with linker 9 and, therefore, more reactive thioester-linker derivatives were developed, such as 17 and 18. Yields for a hindered amine such as Pro-OMe were in the order of 60-70%. Thiol-containing PS-DVB resin 7 has been used for the obtention of P-hydroxyacids by hydrolysis with 0.2 M NaOH in aqueous dioxane [51],... 

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