Chlorine-36, -labeled deuterium

The deuterium isotope effect in the photo-induced chlorine atom exchange reaction with HCl has been investigated by Klein et over the range 30-150 °C by using the competition for chlorine atoms between D2 and DCl (or HCl). The exchange reactions were labeled with radioactive C1. Known mixtures of Cl2, D2, and DCl (or HCl) were irradiated followed by measurement of the residual D2 as well as the activity of the DCl. From this data the rate of the isotope exchange reaction could be determined with respect to the rate of chlorination of deuterium. The results are listed in Table 12 for the reactions... 

The same phenomenon, i.e. that the secondary a-deuterium KIE is determined by the changes in only the shorter reacting bond in the SN2 transition state rather than by the nucleophile-leaving group distance, has been found in a completely different reaction system. Matsson, Westaway and co-workers (Matsson et al., 1996) used ku/k14 carbon incoming nucleophile, chlorine leaving group (Hill and Fry, 1962), and ku/ku a-carbon (Fry, 1970) KIEs to model the transition states for a series of SN2 reactions between p-substituted benzyl chlorides and labelled cyanide ion (reaction (17)). 

The deuterium labels are there so that we can see that the Sn2 reaction is indeed taking place. This reaction is entirely syn even though the methoxide nucleophile must attack alongside the other chlorine atom. The reaction does not stop there since a second methoxide displaces the other chloride—also in a syn fashion. Here too there must be considerable resistance to syn attack as the second methoxide anion must approach alongside the first. 

Photochlorination of 1,1-dichlorocyclopropane (1) yielded a mixture of 1,1,1,3-tetrachloro-propane (2) and 1,14,3,3-pentachloropropane (3), the latter by subsequent chlorination of the primary product tetrachloropropane. The ring opening by a chlorine radical occurred with inversion as demonstrated by the use of deuterium-labeled starting material. Photo-bromination of 1,1-dichlorocyclopropane gave l,3-dibromo-l,l-dichloropropane as the only product. ... 

The preceding reactions dealt with the use of chiral auxiliaries linked to the electrophilic arene partner. The entering nucleophile can also serve as a chiral controller in diastereoselective SjjAr reactions. This approach was successfully employed for the arylation of enolates derived from amino acids. To illustrate the potential of the method, two examples have been selected. Arylation of Schollkopf s bislactim ether 75 with aryne 77 as electrophilic arylation reagent was demonstrated by Barrett to provide substitution product 81 with good yield (Scheme 8.18) [62, 63]. Aryne 77 arises from the orf/jo-lithiation of 76 between the methoxy and the chlorine atom followed by elimination of LiCl. Nucleophilic attack of 77 by the lithiated species 78 occurs by the opposite face to that carrying the i-Pr substituent. Inter- or intramolecnlar proton transfer at the a-face of the newly formed carbanion 79 affords the anionic species 80. Subsequent diastereoselective reprotonation with the bulky weak acid 2,6-di-f-butyl-4-methyl-phenol (BHT) at the less hindered face provides the syn product 81. Hydrolysis and N-Boc protection give the unnatural arylated amino acid 82. The proposed mechanism is supported by a deuterium-labeling experiment. Unnatural arylated amino acids have found application as intermediates for the construction of pharmaceutically important products such as peptidomi-metics, enzyme inhibitors, etc. [64, 65]. 

The mass spectra of TMS derivatives of nucleosides selectively labelled with deuterium and oxygen-18 have been recorded.The position of chlorine atoms in the carbohydrate ring of chloro-deoxy-nucleosides can be established from their mass spectrum. 

---