Organometallic addition to epoxides

I. ORGANOMETALLIC ADDITIONS TO KETONES, CONJUGATED KETONES AND EPOXIDES... 

Organometallic addition to the /V-methoxy-A -methylamide (15) also affords an exceptionally stable tetrahedral intermediate (16) and carbonyl-protecting group, first used in the synthesis of X-206. Deprotonation of the hydrazone in intermediate (16) was subsequently carried out with lithium diisopropylamide. The resulting dianion initiated a novel attack upon epoxide (17) and in the ensuing transformation was followed by tetrahydrofuran ring formation as depicted, in 71% yield, all in one pot (Scheme 4). 

Spectacular enantioselection has been observed in hydrogenation (cf. Section 2.2) [3] and hydrometallation of unsaturated compounds (cf. Section 2.6) [4], olefin epoxidation (cf Section 2.4.3) [5] and dihydroxylation (cf Section 3.3.2) [6], hydrovinylation (cf Section 3.3.3) [7], hydroformylation (cf Section 2.1.1) [4a, 8], carbene reactions [9] (cf Section 3.1.10), olefin isomerization (cf Section 3.2.14) [10], olefin oligomerization (cf Section 2.3.1.1) [11], organometallic addition to aldehydes [12], allylic alkylation [13], Grignard coupling reactions [14], aldol-type reactions [15], Diels-Alder reactions [12a, 16], and ene reactions [17], among others. This chapter presents several selected examples of practical significance. 

Below are described five approaches to epoxide synthesis by way -.if haLohydrins. These halohydrina may be isol ble purifi ble intermediates or they may be transient, unstable species that undergo spontaneous ring closure under the conditions used to generate them. Jho former are typical of (1) addition of hypobalous acids to olefins 111 chemical reduction of a-h Iocarbonyl compounds, and (3) addition if organometallic reagents to o-halocarbonyl compounds the latter,... 

When the allylic alcohol needed for asymmetric epoxidation is unavailable from a commercial source, reasonably general synthetic routes have been developed to allylic alcohols of several different substitution patterns. Good methods are available for the preparation of 3-substituted allylic alcohols, whereas synthesis of 2-substituted allylic alcohols is more problematic. The substrates for kinetic resolution, 1-substituted allylic alcohols, frequently can be derived by addition of alkenyl or alkynyl organometallic reagents to aldehydes followed by modification of the resulting product as required. 

Because organometallic reagents are strong nucleophiles, they react with many other electrophiles in addition to carbonyl groups. Because these reactions always lead to the formation of new carbon-carbon bonds, they are also valuable in organic synthesis. In Section 20.14, we examine the reactions of organometallic reagents with carbon dioxide and epoxides. 

The use of inorganic supramolecular compounds in catalysis has also been successful in recent years. Hupp etal. incorporated a Mn (III)-porphyrin see Porphyrin) epoxidation catalyst inside a molecular square, a system that shows enhanced catalyst stability and substrate selectivity as compared to the free catalyst. In another example, chiral metallocyclophanes were constructed from Pt(PEt3)2 units and enantiopure atropoisomeric l,E-binapthyT6,6 -bis-(acetylenes) and used in enantioselective diethyl zinc addition to aldehydes to afford chiral secondary alcohols. The first organometallic triangle based on Pt(II) and alkyne-di-substituted-binaphthyl system was reported and found to effect asymmetric catalysis reactions of aldehydes to alcohols with excellent conversion rates and enantiomeric excess/ ... 

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). 

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