Carbonyl anion equivalents

The carbonyl anion equivalent is generated from 1 equiv (1 m in THF, —78 <"C) of piperonal dithiomethyl acetal by treatment with 1 equiv of BuLi. After stirring for 40 min at —78 °C, 1 equiv (1 M in TIIF) of the butenolide is slowly added over a period of 30 min. The resulting white suspension is stirred for 3 h at — 78 °C whereupon 1 equiv (1 M in THF) of the 3,4,5-trimethoxybenzyl bromide is rapidly added followed immediately by 1 equiv of TMEDA. The temperature of the mixture is raised to — 20 °C and stirring continued for 10 to 12 h. Standard workup gives the adduct 24 as an amorphous yellow solid crude yield 99% d.r. (trans/cis) >99 <1. 

Oxathiolane 3,3-dioxide (332) metallates in its 2-position to yield an anion which reacts with various electrophiles (alkyl halides and carbonyl compounds) to give substituted oxathiolanes (333) in good to excellent yield (79TL3375). Pyrolysis of these alkylated products affords the corresponding aldehydes or 2-hydroxyaldehydes in addition to sulfur dioxide and isobutylene (Scheme 71). The oxathiolane (332) thus becomes another member of the already burgeoning class of carbonyl anion equivalents. 

The meta acylation of anisole, using a carbonyl anion equivalent as the nucleophile, illustrates the unique regioselectivity available with the Cr(CO)3 activation (equation 31). 

This process has been coupled with meta addition of a carbonyl anion equivalent and the controlled exo addition of the incoming nucleophile to generate acorenone and acorenone B stereospecifically from [(o-methylanisole)Cr(CO)3] (63 Scheme 14).123 The first step is addition of a cyanohydrin acetal anion (64) to the less-hindered meta position in [(o-methylanisole)Cr(CO)3]. Addition of allylMgBr to the resulting ketone, anti-Markovnikov addition of HBr to the alkene, substitution for Br by CN, and coordina-... 

Halo-1,3-dithiane trans-l,3-dioxides (80 X = Cl, Br) act as diastereoselective carbonyl anion equivalents in reactions with aldehydes.117 The scope of the reaction has been explored by varying the temperature, the aldehyde, and the metal used as counterion. Similarly, metal 1,3-dithianides (81 M = Li, Cu1) can be added diastereoselec-tively to chiral aldehydes subsequent hydrolysis yields an a-hydroxyaldehydc.118... 

The scope and limitations of the metal anions of 2-halo-l,3-dithiane trans-1,3-dioxide as diastereoselective carbonyl anion equivalents has been explored with regard to reaction with aldehydes.79 Reactions of metallated trans-, 3-dithiolanc 1,3-dioxide (five-membered ring) with aldehydes under kinetic and thermodynamic control have also been studied and contrasted with those of the metallated monooxide, parent sulfide, and 1,3-dithiane 1,3-dioxide (six-membered ring).80... 

Cyanohydrin trimethylsilyl ethers are generally useful as precursors of carbonyl anion equivalents and as protected forms of aldehydes. Direct conversion of p-anisaldehyde into O-TRIMETHYLSILYL-4-METHOXYMANDELO-NITRILE employs a convenient in situ generation of trimethylsilyl cyanide from chlorotrimethylsilane. A general synthesis of altenic esters is a variant of the Wittig reaction. Ethyl (triphenylphosphoranylidene)acetate converts pro-pionyl chloride into ETHYL 2,3-PENTADIENOATE. 

With arenes bearing a single resonance donor substituent (NR2, OMe, F), the addition is strongly preferred at the meta position, with small amounts of ortho substitution (0-10%). " The meta acylation of anisole, using a carbonyl anion equivalent as the nucleophile, illustrates the unique regioselectivity available with the Cr(CO)3 activation (equation 115). ... 

Lithiobenzothiazole (230) (see Section 3.06.7.10.1) was described to be a carbonyl anion equivalent by Corey and Boger who used it for the preparation of a,) -unsaturated aldehydes and ketones <78TL5,78TL9). As an example, the reaction of (230) with cyclohexanone and dehydration leads to... 

A thermal, rather than hydrolytic, unmasking completes a new aldehyde synthesis using 1,3-oxathiolan 3,3-dioxides as carbonyl anion equivalents. The same reagent may be used to prepare acyloins (Scheme 14)7°... 

The lithiated oxathiolan dioxide (19) has been used as a carbonyl anion equivalent to give high yields of aldehydes from alkyl halides and acyloins from cyclic ketones.The /8-acyl anion equivalent (20 X = Li), which can be prepared from the stannylated diene (20 X = SnRs) by metal exchange, reacts with a variety of electrophiles (E ) to give dienes (20 X = E) in good to excellent yields.The thiophosphate (21) gives a,/3-unsaturated esters in 48—68% yield... 

Another approach to 1,4-dicarbonyl products is also quite versatile and powerful. It involves the conjugate addition of a carbonyl anion equivalent derived from an aldehyde to an a,p-unsaturated carbonyl compound, using either cyanide or thiazolium ion catalysis (Stetter reaction). In the scheme shown (Scheme 14), it is also possible to have R3 = H, by using vinyl ketones or their Mannich base equivalents (225). 

Dithianes derived from aldehydes are important synthetic intermediates because they undergo deprotonation to 2-Iithio-1,3-dithianes which function as carbonyl anion equivalents (umpol-ung reagents). The vinylogons process (eq 4) is a subject of current study. ... 

---