Hydroxy-, derivatives with organometallics

Fluoral hydrate and hemiacetals are industrial products. They are stable liquids that are easy to handle, and they react as fluoral itself in many reactions. Thus, in the presence of Lewis acids, they react in Friedel-Crafts reactions. They also react very well with organometallics (indium and zinc derivatives) and with silyl enol ethers.Proline-catalyzed direct asymmetric aldol reaction of fluoral ethyl hemiac-etal with ketones produced jS-hydroxy-jS-trifluoromethylated ketones with good to excellent diastereo- (up to 96% de) and enantioselectivities. With imine reagents, the reaction proceeds without Lewis acid activation. The use of chiral imines affords the corresponding 8-hydroxy ketones with a 60-80% de (Figure 2.49). ° ... 

In crop protection, the processes to herbicide intermediates (I )-HPOPS and (S)-MOIPA are described. A process catalyzed by an organometallic compound (Ir— ferrocene derivative) has turned out to be superior to the transaminase-catalyzed biocatalytic route to (S)-MOIPA whereas enzymatically-catalyzed aromatic hydroxy-lations with HPOPS as an example are the method of choice. 

The optically active iodide 153 (Scheme 43) can be conveniently prepared from commercially available methyl (S)-(+)-3-hydroxy-2-methylpropionate (154) (see Scheme 41). At this stage of the synthesis, our plan called for the conversion of 153 to a nucleophilic organometallic species, with the hope that the latter would combine with epoxide 152. As matters transpired, we found that the mixed higher order cuprate reagent derived from 153 reacts in the desired and expected way with epoxide 152, affording alcohol 180 in 88% yield this regioselective union creates the C12-C13 bond of rapamycin. 

Synthesis with sacrificial electrodes is employed as a direct method in several other preparations of organometallic compounds and complexes. 3-Hydroxy-2-methyl-4-pyrone derivatives of Sn 1 (and of Zn, Cu, In and Cd as well) were prepared using the metal as an anode. The low oxidation state Sn(II) compound is obtained by direct electrolysis134. 

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],... 

Unlike the corresponding phosphonium salts, addition of sulfonium salts to aldehydes results, not in the alkene products, but in the formation of epoxides (see Section 1.1.5.2). However, sulfones can be used to prepare alkenes, by way of the a-metallo derivatives, in what is termed the Julia olefination (alkenylation). Addition of the organometallic species to an aldehyde or ketone gives a p-hydroxy sulfone which, in the form of its 0-acyl or 0-sulfonyl derivative, undergoes reductive cleavage with, for example, sodium amalgam in methanol to form the alkene. The reaction is regioselective and can be used to prepare mono-, di- and trisubstituted alkenes (2.91). 

Enantiomerically pure 4-alkyl substituted derivatives of tryptophan required for the asymmetric syntheses of ergot alkaloids has been obtained [35]. The author used the method [36] to produce 4-alkyl substituted indoles and combined this organometallic reaction with an enantioselective enzymatic transformation. An efficient eight stage synthesis ofN-benzenesulphonyl-3-(3 -methoxyprop-2 -en-r-yl)-4-(r-hydroxy-2 -trimethylsilymethyl-prop-2 -en-r-yl)-indoles from 4-carbomethoxyindole has been described [37]. The use of these benzylic alcohols for intramolecular cation-olefine cycloadditions yielding either a tetracyclic or a tricyclic product was also demonstrated. 

BF3-OEt2 reverses the usual anti selectivity observed in tbe reaction of crotyl organometallic compounds (based on Cu, Cd, Hg, Sn, Tl, Ti, Zr, and V, but not on Mg, Zn, or B) with aldehydes (eq la) and imines (eq lb), so that homoallyl alcohols and homoallylamines are formed, respectively. " The products show mainly syn diastereoselectivity. BF3-OEt2 is the only Lewis acid which produces hydroxy- rather than halo-tetrahydropyrans from the reaction of aUyl-stannanes with pyranosides. The BF3-OEt2 mediated condensations of y-oxygenated allylstannanes with aldehydes (eq Ic) and with activated imines (eq Id) affords vicinal diol derivatives and 1,2-amino alcohols, respectively, with syn diastereoselectivity. The activated imines are obtained from... 

All nucleophilic substitutions show that in pyridine and its derivatives as free bases the 2- and 4-positions are more reactive than the 3-position. Organometallic compounds generally effect 2-substitution (pp. 200, 220) and the Tschitschibabin amination and hydroxy la tion reactions also occur mainly at C(2) (pp. 206, 234). However, these reactions cannot be taken to imply superior electrophilic power in C(2) as compared with C(4), for the issue is confused in each case by mechanistic problems as well as the precise nature of the reagent, that of the initial step is uncertain, and subsequent stabilization of one transition state rather than another by the formation of an addition compound may be occurring. As evidence about the intrinsic electrophilic properties of individual nuclear positions these reactions are valueless. 

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