Stereochemical consequences of C-methylation of 1-methylphosphorinane and its sulfide and oxide: a carbon-13 and phosphorus-31 nuclear magnetic resonance study

Abstract

Placing a methyl at the 3 or 4 position of 1-methylphosphorinane results in conformational equilibria for both the cis and trans isomers that are strongly biased toward the form with equatorial C-methyl. This remains true when the phosphines are converted to sulfides, oxides, or methiodides. The steric demand of C-methyl is therefore considerably greater than that of P-methyl, a fact predicted fpr 1-methylphosphorinane by its AGO value of +0.35 kcal/ mol. I3C NMR spectroscopy was especially helpful in qualitatively analyzing the equilibria; the C-methyl and its carbon of attachment in a pair of isomers had little chemical shift variability, while P-methyl differed by 4-6 ppm, always with the axial methyl relatively upfield. Both the sulfides and the oxides have ring carbons 3 and 5 at higher field (2-3 ppm) when the sulfur or oxygen atoms are axial. This greater y effect for a single-atom substituent on phosphorus over a methyl group has been observed previously for the case of S, but not for 0. While 31P NMR shifts were sensitive to the stereochemistry about phosphorus, no consistency in the direction of the effect was present. For the phosphines, axial methyl caused the expected relatively upfield shift. This was observed also for the sulfides, hut the reverse effect prevailed for the oxides.Phosphorus-substituted phosphorinanes are of considerable interest because of the predominance of the conformer with axial substituent, over that with equatorial a t room temperature.2 For the 1-methyl derivative, the equilibrium constant (a s e) is estimated to be about 0.55, which gives AGO = +0.35 kcal/mol at 27 "C. This unusual result stems from a combination of a rather low enthalpy difference for the conformers (AHo = -0.68 kcal/mol) and a significant entropy effect (ASo = -3.4 eu). 1-Methylarsenane was later reported by another group to exhibit similar p h e n~m e n a .~We have continued our investigation of the 1-methylphosphorinane system by considering the consequences of placing methyl a t either the 3 or the 4 position, and then of adding sulfur, oxygen, or methyl to phosphorus to increase its covalency in these compounds. The synthesis and spectral properties of all of these compounds are reported in the present paper. Our major probe of the conformational changes occurring in these families has been I3C NMR spectroscopy; we have previously employed this technique for hydroxy4 and keto5 derivatives of phosphorinanes and have witnessed a number of useful effects. 31P NMR spectroscopy has also figured in our earlier studies and we have examined our new C-methyl compounds by this technique also.The spectral data we have accumulated are best interpreted on the basis of perturbation of the conformational equilibrium for the parent 1-methylphosphorinane (1). Thus, a more CH la l bspace-demanding group such as CH3 (AGO = -1.7 kcal/mol in cyclohexanes; for thianes,6 -1.80 f 0.10 for 4-CH3 and 1.40 f 0.07 for 3-CH3) placed on ring carbon 4 should control the equilibrium and the P-CHs group will be forced into greater oc...

The preparation of 3-substituted-1,5-dibromopentanes as precursors to heteracyclohexanes

“…Some thianes IV are found in petroleum distillates [ 9 ] and several have been used for the preparation of sulfones [ 7 , 10 – 11 ], sulfoxides [ 11 – 12 ], and sulfonium derivatives [ 13 ]. The latter, as well as silacyclohexanes V [ 14 ] and phosphorinanes VI [ 15 – 16 ], have been used in conformational and stereochemical studies.…”

“…Dibromides I can also be obtained by the ring-opening of tetrahydropyrans VIII under the same conditions employed for the diols VII [ 2 , 12 , 21 – 22 ], or via phase-transfer catalysis conditions with a phosphonium salt [ 23 ]. Piperidines III (Y = H) can undergo degradation to form dibromides I although this process is typically less efficient [ 12 , 14 – 15 ]. The piperidine ring can be reconstituted by ring-closure of I with an appropriate amine or aniline Y–NH 2 [ 2 , 22 ].…”

“…The piperidine ring can be reconstituted by ring-closure of I with an appropriate amine or aniline Y–NH 2 [ 2 , 22 ]. The thianes IV are typically obtained from I or from II by reaction with Na 2 S [ 9 – 10 12 – 13 ], whereas the silacyclohexanes V and phosphorinanes VI are prepared by reacting the Grignard reagent derived from I with dichlorosilanes [ 14 ] or phosphonous dichlorides [ 15 ], respectively ( Fig. 1 ).…”

Conformational Analysis of the 1,3‐Oxaphosphorinanes Formed from α,β‐Unsaturated Aldehydes and the (Hydroxymethyl)phosphines RP(CH2OH)2 (R = Ph or CH2OH)

“…and S8) shows there are just four diastereomers (out of a possible eight) and implies that either the addition of a deuteron, or generation of chirality at P1 or C4, occurs stereoselectively—the geometry at C6 is considered irrelevant because phosphine attack at the CC bond from both sides of a planar α,β‐unsaturated aldehyde will generate equal amounts of ( R ) and ( S ) chirality. Based on the literature data and NMR data obtained, the structures of A , B , C and D (for both 5a and 5b ) are assigned as shown on the left side of Scheme with ( RS )/( SR ) chirality at C5 and C6 − see below; the corresponding diastereomers with ( RR )/( SS ) chirality at C5 and C6 are shown in Figure S9; only one enantiomer, with ( S ) chirality at the P‐atom, is shown for all the diastereomers. The possible conformers labeled “*” in the middle of Scheme are considered to be undetected in the reaction mixtures.…”

“…Evidence for the proposed structures of A , B , C , D derives from knowledge of phosphorinane‐type compounds, where the orientation of a substituent on the P‐atom has a dramatic effect on chemical shifts and 2 J PC values of the ring C5‐atom: an axial orientation gives 13 C resonances with 2 J PC ~ 0 Hz upfield to those of an equatorial substituent with 2 J PC values of 5–8 Hz . 13 C{ 1 H} NMR data for 5a reveal that the H5 proton of isomers A and B correlates with the corresponding C5 resonance that shows no 2 J PC coupling and is seen, respectively, as a triplet at δ C 30.8 and 33.7 with 1 J CD = 19.7 Hz (Table , Fig.…”