Silyl carbonates synthons

Silyl carbonates (124) possessing an anion-stabilizing function have been developed by Tsuji and co-woikers as TMM synthons in [3 + 2] reactions. In this case the in situ generated alkoxide serves as a... 

Alkyl halides and sulfonates are the most frequently used alkylating acceptor synthons. The carbonyl group is used as the classical a -synthon. O-Silylated hemithioacetals (T.H. Chan, 1976) and fomic acid orthoesters are examples for less common a -synthons. In most synthetic reactions carbon atoms with a partial positive charge (= positively polarized carbon) are involved. More reactive, "free carbocations as occurring in Friedel-Crafts type alkylations and acylations are of comparably limited synthetic value, because they tend to react non-selectively. 

Treatment of O-silyl enols with silver oxide leads to radical coupling via silver enolates. If the carbon atom bears no substituents, two such r -synthons recombine to symmetrical 1,4-dicarbonyl compounds in good vield (Y. Ito, 1975). 

If a Michael reaction uses an unsymmetrical ketone with two CH-groups of similar acidity, the enol or enolate is first prepared in pure form (p. llff.). To avoid equilibration one has to work at low temperatures. The reaction may then become slow, and it is advisable to further activate the carbon-carbon double bond. This may be achieved by the introduction of an extra electron-withdrawing silyl substituent at C-2 of an a -synthon. Treatment of the Michael adduct with base removes the silicon, and may lead as well to an aldol addition (G. Stork, 1973, 1974 B R.K. Boeckman, Jr., 1974). 

Nucleophilic Reactions.—Attack on Saturated Carbon. Selected examples of the Arbusov reaction include phosphorylation of the chloroacetophenones (1) to give phosphonates, which cyclized to (2) in the presence of acid chlorides,1 formation of the azodiphosphonate (3) from 2,2 -dichloro-2,2 -azopropane,2 3 and the reaction of 2-chloro-3,4-dihydro-3-oxo-2//-l,4-benzothiazine (4) with triethyl phosphite to give the 2-phosphonate (5), which is used as an olefin synthon.8 Bis(trimethylsilyl) trimethylsiloxymethylphosphonite (6) has been synthesized by silylation of hydroxy-methylphosphonous acid, and, as expected, undergoes a normal Arbusov reaction with alkyl halides to give the phosphonates (7).4 This series of reactions, followed by... 

A CH-group, which bears vinyl and sulfide substituents, is acidic enough to be metallated by strong bases. Other d3-synthons may contain two activating functional groups in Imposition ( homoenolate -equivalents). Only one of the a-carbons is deprotonated under appropiate conditions (e.g. succinic diesters). Ano ther possibility is an acidic carbon and a non-acidic functional group in 1,3-positions (e.g. propargyl derivatives). Silyl ethers of a, -unsaturated alcohols can also be converted to anions, which react as d3-synthons (W. Oppolzer, 1976). 

The asymmetric synthesis of a-hydroxymethyl carbonyl compounds is currently the subject of considerable interest because of their versatility as dual-function chiral synthons. There have been no reports of successful enantioselective hydroxymethylations of prochiral metal enolates with formaldehyde because of the instability and small steric size of gaseous formaldehyde. The author and Yamamoto et al. developed the enantioselective alkoxymethylation of silyl enol ethers by introducing suitable carbon-electrophiles in place of the activated-protons of LBA [142]. 

The Lewis acid-catalyzed conjugate addition of silyl enol ethers to a,y3-unsaturated carbonyl derivatives, the Mukaiyaraa Michael reaction, is known to be a mild, versatile method for carbon-cabon bond formation. Although the development of catalytic asymmetric variants of this process provides access to optically active 1,5-dicarbonyl synthons, few such applications have yet been reported [108], Mukiyama demonstrated asymmetric catalysis with BINOL-Ti oxide prepared from (/-Pr0)2Ti=0 and BINOL and obtained a 1,4-adduct in high % ee (Sch. 43) [109]. The enantioselectiv-ity was highly dependent on the ester substituent of the silyl enol ether employed. Thus the reaction of cyclopentenone with the sterically hindered silyl enol ether derived from 5-diphenylmethyl ethanethioate proceeds highly enantioselectively. Sco-lastico also reported that reactions promoted by TADDOL-derived titanium complexes gave the syn product exclusively, although with only moderate enantioselectiv-ity (Sch. 44) [110]. 

Shinokubo, H., Miura, K., Oshima, K., Utimoto, K. lert-ButyIdimethylsilyIdichloromethyllithium as a dichloromethylene dianion synthon. 1,3-Rearrangement of silyl group from carbon to oxide. Tetrahedron Lett. 1993, 34,1951-1954. 

The aldol reachon is one of the most efficient methods for extending the carbon framework of an organic synthon. Since the discovery of the Lewis acid-catalyzed asymmetric aldol reaction of silyl enol ethers by Mukaiyama, numerous variations of this type of reaction have been reported [80]. Recently, more attention has been focused on the development of new organocatalysts for the asymmetric direct aldol... 

Dioxabicyclo[3.2.1]octane, the carbon skeleton of 1,6-anhydropyranose, is present in plant extracts and pheromones, and it is a crucial fragment in orally active 5-lipoxygenase inhibitors. The synthon 6,8-dioxabicyclo[3.2.1]octane-3-one (1102) is readily prepared from ( S)-malic acid-derived diol 45a, as shown in Scheme 162 [234]. Silylation of ketone 1099 with TBS triflate provides the kinetically derived silyl enol ether 1100 (10 1 kinetic vs. thermodynamic selectivity) in high yield. Lewis acid cyclization of the cyclic ortho ester 1100 affords the bicycloketone 1102 in 25.5% overall yield starting from (iS)-malic acid. 

Silylformylation of olefins and alkynes can be regarded as the silicon version of hydroformylation. The reaction involves the concomitant introduction of a silyl group, derived from a hydrosilane, and a formyl group derived from insertion of carbon monoxide, thus producing functionalized olefins and dienes, which are useful synthons. ... 

With few exceptions, substitutions on carbon have been achieved only at an early stage of the synthetic process, that is, on the starting o-carborane, but not by direct reaction at the [3,3 -Co( 1,2-C2B9H],)2] cage. Recently, the isolation of the synthon C<.-silyl-substituted cobaltabisdicarbollide Cs[l,l -p.-SiMeH-3,3 -Co(l,2-C2B9H,o)2] that allows the preparation of boron-rich polyanionic macromolecules via hydrosilylation reactions of vinyl- and allyl-terminaled dendrimers has been reported. ... 

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