Organometallic additions

The stereoselectivity of organometallic additions with carbonyl compounds fits into the general pattern for nucleophilic attack discussed in Chapter 3. With 4-r-butylcyclohex-anone, there is a preference for equatorial approach but the selectivity is low. Enhanced steric factors promote stereoselective addition. 

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

A similar oxazolidine-based strategy was employed in the syntheses of R-(+)-anatabine (84) and (+)-benzomorphan (85), utilizing Zincke-derived salts 80 and 81, respectively (Scheme 8.4.26). In these cases, borohydride reduction, followed by cyclization, led to oxazolidines 82 and 83 as substrates for organometallic addition and subsequent elaboration to the natural products... 

Organometallic Addition/Reduction Sequence on Chiral o -Aminonitriles... 

The isoborneol-10-sulfonamide unit represents a new type of chiral structure that has been successfully used in different reactions of organometallic addition to aldehydes with excellent results in some cases. In particular, this unique type of ligand has been investigated by Yus and Ramon for the enantioselective... 

Other bonds that merit attention are those connecting C(7) through C(ll). These could be formed by one of the many methods for the synthesis of ketones. Bond disconnections at carbonyl centers can involve the 0=C-C(a) (acylation, organometallic addition), the C(a)-C((3) bond (enolate alkylation, aldol addition), or C((3)-C(7) bond (conjugate addition to enone). 

In the case of TGT structures which are acyclic or which contain isolated rings, the disconnection of non-ring bonds must be examined to identify those disconnections which may be most effective on topological grounds. However, for such acyclic disconnections the topological factors may be overshadowed by other structural considerations. For instance, if a powerful stereosimplifying disconnective transform, such as stereospecific organometallic addition to carbonyl... 

The reaction of trialkylboranes with 1,4-benzoquinones to give in quantitative yield 2-alkylhydroquinones was the first reaction of this type occurring without the assistance of a metal mediator [81,82], An ionic mechanism was originally proposed but rapidly refuted since the reaction is inhibited by radical scavengers such as galvinoxyl and iodine [83]. This procedure is in many cases superior to the more widely use organometallic additions. For instance, when primary and secondary alkyl radicals have been used and afford the addition products in high yield (Scheme 33) [84],... 

As part of a strategy of employing monosaccharides as a convenient source of chirality, organometallic additions to protected L-erythrulose derivatives have been carried out. Employing silyl, benzyl, trityl, and acetonide protecting groups, the diastereoselectivities obtained are discussed in terms of chelation to the a-and/or the /3-oxygen, and are compared with results for similar aldehydes. 

Lactonization of alcohols derived by organometallic addition to 2-formyl amides, lactol formation from 2-formyl amides themselves and lactam formation from their nitrogen counterparts are also useful synthetically. 

A biaryl propionic acid derivative containing a furan ring as a prominent feature has antiinflammatory activity. The patented synthesis involves a straightforward organometallic addition of ethyl lithioacetate to aldehyde 12 followed by saponification... 

The landmark discovery of ferrocene by Kealy and Paulson in 1951 marked the beginning of modern organometallic chemistry. The first organometallic addition polymer was polyvinyl-ferrocene synthesized by Arimoto and Haven in 1955. While polyvinylferrocene (structure 11.32) had been synthesized it was about another decade until the work of Pittman, Hayes, and George, and Baldwin and Johnson allowed a launch of ferrocene-containing polymers. 

Free radical addition to oximes and oxime ethers emerged as a useful alternative to addition of organometallic reagents, particularly for intramolecular reactions. The most important advantage of free radical V5. organometallic addition is its tolerance for almost any functional group (with the exception of thiocarbonyl and iodoalkyl functions). 

With 2-unsubstituted quinazolines 426 (X = O or S), organometallic addition occurs at the 2-position to give 2-alkyl-l,2-dihydroquinazolines 428 <2005JSF121, 2005S2951>, while with 2-alkoxyquinazolines addition of orga-nometallics occurs at the 4-position, as demonstrated by the addition of lithium phenylacetylide to the 2-methoxy-methyl quinazolinone 429 which gave a quantitative yield of a tautomeric mixture of the 3,4- and 1,4-dihydro derivatives 430 and 431 <2004JA5427>. 

The pattern of organometallic addition to quinazolinones follows that for the quinazolines, with both 4(377)-quinazolinones 434 (X = O) and 4(377)-quinazolinethiones 434 (X = S) undergoing addition at the 2-position. Both 3-unsubstituted (R = H) and 3-acylamino (R =MeCONH or /-BuCONFl) derivatives 435 have been prepared <1996JOC656, 2004M323, 2005JSF121>. 

The furanoterpene 15-acetoxytubipofuran 12 shows cytotoxicity against B-16 melanoma cells. E. Peter Kiindig of the University of Geneva has reported (J. Am. Chem. Soc. 125 5642, 2003) a concise asymmetric synthesis of 12, based on the addition of lithio ethyl vinyl ether to the chromium tricarbonyl-activated benzaldehyde 10. In the course of the organometallic addition, five carbon-carbon bonds are formed. 

Addition (Organometallic addition occurs exclusively here as well as many organic additions)... 

Indol-3-ylcarbinols can also be reduced using Et3SiH-TFA. Aryl indolyl-3-ylcarbinols can be formed in situ from 2-alkylindoles and benzaldehydes. These reactions, when run in tandem, provide a versatile route to 3-benzylin-doles[11]. Indole itself undergoes reduction to indoline under these conditions. lndol-3-ylcarbinols can also be generated by organometallic additions to 3-acylindoles[12]. 

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