Base-Dependent Regio- and Diastereoselective Alkylation of Chiral Perhydro 1,3,2-Oxazabenzophosphorinane-2-oxides Derived from (-)-8-Benzylamino Menthol

Abstract

The regioselectivity in the alkylation of chiral perhydro 1,3,2-benzoxazaphosphorinane-2-oxides is dependent on the base used for deprotonation. The ethyl oxazaphosphorinanes are benzylated at the nitrogen substituent after deprotonation with n-BuLi, but a to the phosphorous atom by deprotonation with LDA. On the contrary, the benzyl oxazaphosphorinane is alkylated a to the phosphorous atom after deprotonation with both, n-BuLi or LDA.

Synthesis and Conformational Analysis of Saturated cis‐and trans‐1,3,2‐Benzodiazaphosphinine 2‐Oxides

“…Thus both a and b epimers of compounds 8, 10 and 12 are assumed to predominantly populate chair heteroring conformations. Consistently with this, these derivatives generally show large 3 J 4-Hax,4a-H , 3 J P,4-Heq and 3 J P,C-8 and small 3 J P,4-Hax values (Table 1 and Table 5) as expected for double-chair conformations from Karplus-like dependencies of 3 J on the relevant torsion angle. As already noted, the 1 J P,i-C values ( Table 5) clearly indicate that the phenyl substituent is equatorial in the case of epimers a and axial in the case of epimers b, which is also in agreement with a predominant chair heteroring conformation.…”

“…The values of P I (N-in) and P I (N-out) were obtained from compounds 13a and 17b, respectively. These compounds display extreme values for the parameters P I within the cis-fused series and their 3 J H,H values are also similar to the 3 J Hax,Hax and 3 J Heq,Heq values of the trans-fused compounds.…”

“…Similarly, compounds 12a and 12b (R 2 = CH 3 ) clearly exhibit smaller values of 3 J P,C-8 (6.1 and 4.9 Hz, respectively) than 8,10a,b (9.2-10.1 Hz, R 2 = H) due to N-methyl substitution in the corresponding coupling pathway. The chair heteroring conformation for 12a,b is nevertheless evident from the other relevant 3 J values. The substituents at N1 and N3 can be either equatorial or axial and the positions are interconvertible through nitrogen inversion.…”

“…The conformational processes present in the compounds studied were observed to be fast on the NMR timescale at 25°C in CDCl 3 . Thus, only population-weighted averages of the 1 H, 13 C and 31 P NMR signals were observed.…”

“…[1] Alkylation of phosphorus-stabilized carbanions derived from 1,3,2-oxazaphosphinane 2-oxides have proved to be an efficient method for the diastereoselective construction of carbon-carbon bonds. [2,3] However, the analogous 1,3,2-diazaphosphinane ring system has been less thoroughly studied either from a pharmacological or stereochemical point of view. [4] The 1,3,2-N,N,P analogue of cyclophosphamide was found to have no significant anticancer activity.…”