Alcohols Organozinc reagents

The 2-(l-alkynyl)oxirane 78 reacts with an organozinc reagent yielding the /9-allenylic alcohol 79[35]. 

Even if hundreds of chiral catalysts have been developed to promote the enantioselective addition of alkylzinc reagents to aldehydes with enantioselectivities over 90% ee, the addition of organozinc reagents to aldehydes is not a solved problem. For example, only very few studies on the addition of vinyl groups or acetylides and even arylzinc reagents to aldehydes have been published, in spite of the fact that the products of these reactions, chiral allylic, propargylic and aryl alcohols, are valuable chiral building blocks. 

Organozinc reagents have been used in conjunction with a-bromovinylboranes in a tandem route to Z-trisubstituted allylic alcohols. After preparation of the vinylborane, reaction with diethylzinc effects migration of a boron substituent with inversion of configuration and exchange of zinc for boron.176 Addition of an aldehyde then gives the allylic alcohol. The reaction is applicable to formaldehyde alkyl and aryl aldehydes and to methyl, primary, and secondary boranes. 

The first asymmetric procedure consists of the addition of R2Zn to a mixture of aldehyde and enone in the presence of the chiral copper catalyst (Scheme 7.14) [38, 52]. For instance, the tandem addition of Me2Zn and propanal to 2-cyclohexenone in the presence of 1.2 mol% chiral catalyst (S, R, R)-1S gave, after oxidation of the alcohol 51, the diketone 52 in 81% yield and with an ee of 97%. The formation of erythro and threo isomers is due to poor stereocontrol in the aldol step. A variety of trans-2,3-disubstituted cyclohexanones are obtained in this regioselective and enantioselective three-component organozinc reagent coupling. 

The chiral f5-dialkylamino alcohol DAIB serves as an efficient asymmetric catalyst for the addition of organozinc reagents to aldehydes. The reaction of diethylzinc with benzaldehyde in the presence of 2 mol % of (2S)-(-)-DAIB to give (S)-1-phenyl-1-propanol in 89% ee is described in the procedure which follows. DAIB exhibits the... 

In early 1990 we began to work on catalyzed carboligations using organozinc reagents [1]. The reactions commonly involved diethylzinc 2, which was added enantioselectively to aldehydes 1 affording secondary alcohols 3. Initially, bipyridine 4 [2-6], pyridine 5 [3], and sulfoximines 6 [7] were applied as catalysts, which in some cases led to enantioselectivities greater than 95% ee [8, 9]. 

Synopsis of Goldfuss and Houk (1998) Origin of Enantioselectivities in Chiral /i-Arnino Alcohol Catalyzed Asymmetric Additions of Organozinc Reagents to Benzaldehyde PM3 Transition State Modeling . 

Chiral A-amidino-l,2,3,4-tetrahydropyridines undergo a stereoselective epoxidation-nucleophilic opening sequence with either alcohols or organozinc reagents to give 2,3,6-trisubstituted piperidines where the relationship between the 2- and 3-positions is cis (Equation 15) <2005OL2747>. 

Particularly challenging is the use of chiral ligands in order to impose enan-tiocontrol on a Reformatsky reaction. Although preparatively useful levels of asymmetric induction have been described in the recent literature by using enantiomerically pure amino alcohol ligands43 this reaction has not yet reached a similar level of perfection as the enantioselective addition of other organozinc reagents to aldehydes in the presence of the same type of additives. Some selected examples of stereoselective Reformatsky type reactions which delineate the present state of the art are summarized in Scheme 14.6. 

In the reaction of allylic organozinc reagents with carbonyl derivatives (e.g., diisobutyl ketone), isomerization of the branched product (XXX) occurs to the thermodynamically more stable linear product (XXXI) (333). The ratio of linear to branched alcohol increases with longer reaction time, and this was taken as evidence that the branched alco-... 

Several papers are concerned with the threo-erythro stereoselectivity of the reaction of allylic organozinc reagents with carbonyl compounds. The addition (involving allylic rearrangement) of crotylzinc derivatives to various aldehydes occurs stereoselectively, and the relative amount of tAreo-alcohol increases with increasing steric demand of the group R tert-Bu, S4% f-Pr, 707o n-Bt, 46%) and in the sequence of metals Mg < Zn < Cd 3, 7). The temperature or the polarity of the solvent... 

The stereochemistry of addition of an allylic organozinc reagent to a carbonyl group has received considerable attention. Both diallyl- and dicrotylzinc in their reactions with alkyl-substituted cyclohexanones display a strong preference for equatorial attack (formation of the rfl -alcohol) on the carbonyl group (5, 6), e.g.,... 

XXXV) and (XXXVI) indicates the occurrence of heterolytic cleavage of the C-3-C-4 bond of the amine (XXXIV). In the presence of an excess of allylzinc bromide, only the amines (XXXIV) and (XXXVI) are isolated. Similar types of reactions have been observed in the reactions of allylic organozinc reagents with unsaturated alcohols (333). The reaction of allylzinc bromide with the branched alcohol (XXXVII) forms both the allylcarbinol (XXXVIII) and the rearranged linear alcohol (XXXIX) (333). 

The organozinc reagent derived from 3-bromo-l-butyne which has the allenic structure (XLII) affords a mixture of three isomeric alcohols upon reaction with diisopropyl ketone, indicating the strong tendency of rearrangement in the systems (171). The proportion of allenic alcohol... 

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