Nucleophiles sulfur-stabilized

Sulfur-stabilized ylides underwent photodriven reaction with chromium alkoxy-carbenes to produce 2-acyl vinyl ethers as E/Z mixtures with the E isomer predominating (Table 22) [ 121-123]. The reaction is thought to proceed by nucleophilic attack of the ylide carbon at the chromium carbene carbon followed by elimination of (CO)5CrSMe2. The same reaction occurred thermally, but at a reduced rate. Sulfilimines underwent a similar addition/elimination process to produce imidates or their hydrolysis products (Table 23) [ 124,125]. Again the reaction also proceeded thermally but much more slowly. Less basic sulfilimines having acyl or sulfonyl groups on nitrogen failed to react. 

Then, substitution of the sulfur atom of Cys with an oxygen would greatly decrease the rate of reaction, because nucleophilicity, anion-stabilizing effect and proton-donating ability of OH group are far smaller than that of an SH group. 

Radical cations of 2-alkylidene-l,3-dithianes can be generated electrochemically by anodic oxidation using a reticulated vitreous carbon (RVC) anode <2002TL7159>. These intermediates readily react with nucleophiles at C-1. Upon removal of the second electron, the sulfur-stabilized cations were trapped by nucleophilic solvents, such as MeOH, to furnish the final cycloaddition products. Hydroxy groups <20010L1729> and secondary amides <2005OL3553> were employed as O-nucleophiles and enol ethers as C-nucleophiles (Scheme 50) <2002JA10101>. 

Most of the applications of sulfoxides in synthesis make use of the reactions of sulfur-stabilized carbanions with electrophiles [385, 386]. Thus the methylsulfinyl methylene carbanion, conveniently generated through the interaction of sodium hydride with DMSO [387], is a powerful nucleophile. 

The synthesis of 4-alkyl thioketones is possible by exploiting the stabilizing effect of a sulfur atom upon an adjacent carbanionic center. Ambident allylic anions react so that conjugate addition proceeds exclusively with the a-carbon of the nucleophile,129 243 244 as illustrated in equation (S3) 245 arylsulfinyl and arylsulfonyl groups normally246 behave similarly.247-249 Sulfur-stabilized vinylic carbanions can be prepared and function as Michael donors in difunctionalization sequences.250... 

The stereochemical outcome of the conjugate addition of sulfur-stabilized nucleophiles to the 5-lactam unit of tetrahydrobenzo[a]benzoquinolizines (83) has been (g) shown to depend on the nature of the substituent at the angular position (R1) thus,... 

Conversion of Phosphorus- or Sulfur-Stabilized C Nucleophiles with Carbonyl Compounds Addition-induced Condensations... 

Cyclooctyne (14) adds bromine to give l,2-dibromo-cis-cyclooctene93) this is presently the only route to prepare a pure 1,2-dihalocyclooctene. The addition of bromine and iodine to (31) leads to the unexpected products (54) apparently trans-annular attack of the cationic intermediate (55) by the nucleophilic sulfur produces a strained sulfonium ion which stabilizes itself by ring opening to (54)201). 

The closure of the macrocyclic ring by means of an intramolecular 8 2 reaction is a straightforward approach, and sulfur-stabilized carbanion alkylation has been successfully applied in the synthesis of 14-membered cembranoids. The synthesis of nephthenol (40) and cembrene A (59) is an example of this methodology. In Li and Yue s report, the total synthesis of ( )-sarcophytol M (17) was achieved from ger-aniol (137) through 12 steps and in 8.9% overall yield with an intramolecular nucleophilic addition of a sulfur-stabilized carbanion to a ketone as a key step. This example is the first of the closure of a macrocyclic ring with the intramolecular nucleophihc addition of a sulfur-stabilized carbanion to a ketone (Scheme 6-7). 

The closure of the macrocyclic ring by means of an intramolecular Sn2 reaction is a straightforward approach. For example, an intramolecular nucleophilic addition of sulfur-stabilized carbanion to epoxide was used in the synthesis of nephthenol (40) and cembrene A (59) from trani.tran -geranylhanlool (144) (Scheme 6-10). ... 

The first enantioselective total synthesis of l -(—)-cembrene A (59) and / -( )-nephthenol (40) were achieved by employing an intramolecular nucleophilic addition of sulfur-stabilized carbanion to asymmetric epoxide as the key step, starting from L-serine (Scheme 6-13). ... 

The steric effect on regioselectivity shows clearly in the series in Eq. (31), Table 4. Comparing similar anion type, except for size, entries 1, 3, and 7 show that ortho substitution is very signiflcant with a primary carbanion but essentially absent with a tertiary cyano-stabilized anion. It is striking that as the size of the alkyl substituent on the arene increases, not only is ortho substitution disfavored, but meta is as well compare entries 3-6 and compare 7-9. With the very large CH(t-Bu)2 group (entry 9), only para substitution is observed. Regioselectivity is also dependent on the electronic nature of the nucleophile. Most remarkably, addition of the primary sulfur-stabilized anion shows nearly equal... 

Reversibility, even at low temperatures, has been shown to be fast for stabilized carbanions (e.g., nitrile stabilized carbanions, ester enolates) whereas (most) sulfur stabilized carbanions and simple organo lithium compounds add irreversibly. Nevertheless protonation is more rapid than anion dissociation even for the first category of anions mentioned and nucleophile addition/proto-nation reactions allows efficient conversion to a dearomatized product. 

---