4767
J. Org. Chem. 1995,60,4767-4773
Study of the Conformational Equilibria of 2-Z-3-Methyl-1,3,2-oxazaphosphorinanes. Steric and Stereoelectronic Influences on the Orientation of the Me2N Substituent on Three-CoordinatePhosphorus Yande Huang, Jaehoon Yu, and Wesley G. Bentrude* Department of Chemistry, University of Utah, Salt Lake City, Utah 84112 Received March 2, 1995@
The conformations of a series of 1,3,2-oxazaphosphorinanescontaining three-coordinate phosphorus, 1-9, have been determined by the use of 'H, 31P, and 13C NMR spectroscopy. The rings were substituted at ring nitrogen, N(3), with a methyl group to compare its effect on conformational energies with those of 1,3,2-oxazaphosphorinanesreported earlier that featured a larger substituent a t N(3), Ph or i-Pr. Quite expectedly, like those rings previously studied with Ph or i-Pr at N(3), a Me0 or (CF3)zCHO substituent at phosphorus has a strong preference to be axial on a chair-form ring, 1-4, cis-7, and cis-8, or pseudoaxial on a ring in a twistmoat conformation, trans-7. However, when MezN is attached to phosphorus, the newly studied N(3)Me rings display a chair-chair conformational equilibrium, 10 11, with the MezN equatorial ring, 11,mildly dominant (58/42, 5; 65/35, 6). This contrasts with ratios of 17/83 and 20/80 for the corresponding N(3)Ph analogs, A, and 23/77 for the N(3)-i-Pr compound, B. The observed change in the free energy of the equilibrium 10 s 11, 1.2-1.3 kcaYmol, is ascribed to the dominant influence of a decrease in repulsion experienced in conformation 11 between the equatorial MezNP and the smaller Me a t N(3) (MezN(eq)/N(S)Medestabilization) compared to that experienced with the N(3)Ph and N(3)i-Pr analogs. This steric influence of N(3) substituents on the equilibrium 10 11 is opposite to that found for four-coordinate phosphorus containing 1,3,2-oxazaphosphorinanesin which MezNP(ax)/ N(3)Ph repulsions that destabilize 10 appear to be dominant.
Introduction
nate 2-oxo-1,3,2-oxazaphosphorinanes substituted at ring nitrogen with phenyl.4 The structural properties of 1,3,2-dioxa- and 1,3,2These surprising results for A and B were ascribed oxazaphosphorinanes containing three- and four-coorditentatively to dominant, destabilizing, vicinal steric nate phosphorus have been widely studied.' In these ring repulsions between the 3-phenyl and 3-isopropyl substitsystems, both steric and stereoelectronic factors play uents on ring nitrogen and the equatorial MezN which important roles in determining the conformations of the are relieved when the MezN is A second factor six-membered ring and the orientation of the substituent that generally favors axial placement of groups on threeon phosphorus. Recently, we reported on the conformacoordinate phosphorus in 1,3,2-oxazaphosphorinanesis tional properties of a series of three-coordinate 2-Z-3anomeric stabilization5from overlap of the ring nitrogen phenyl-1,3,2-oxazaphosphorinanes, A (R1= R2 = H; Me; electron lone pair, n, with the axial PN 8 orbital (nN ~ - B u ) .Unexpectedly, ~ the MezN substituent, Z, on phosCP~ stabilization). N This stabilization likely is enhanced phorus in this series displayed a 0.8-1.1 kcaymol axial in 1,3,2-oxazaphosphorinanes,compared t o their 1,3,2preference. A similar result, previously r e p ~ r t e d ,was ~ dioxaphosphorinane counterparts (no O*PN stabilizaconfirmed for 2-(dimethylamino)-3-isopropyl-1,3,2-oxazation), by the higher energy of the nitrogen lone pair phosphorinane, B.2 These findings contrast with the participant. Furthermore, the X-ray crystal structure of A (R1= Rz = Me) with axial PNMez shows 1,3-syn axial interactions between axial PNMez and the axial hydrogens a t carbons 4 and 6 to be accommodated by the ring isoPr Y h flattening associated with the relatively long C(4)-N(3) B A and N(3)-P bonds.2 At the same time, the axial MezN equatorial preference of the MezN group in threeassumes a stereoelectronically favorable conformation coordinate 1,3,2-dioxaphosphorinanes'and four-coordiabout the Me2N-P bond that is not available to 1,3,2dioxaphosphorinanes.
-
-
&gz
Q-"
Abstract published in Advance ACS Abstracts, July 1, 1995. (1)Reviews may be found in: (a)Bentrude, W. G. In Conformational Studies of Six-MemberedRing Carbocycles and Heterocycles; Juaristi, E., Ed.; VCH Publishers: New York, 1995;pp 245-293. (b) Bentrude, W. G. In Phosphorus-31 NMR Spectral Properties in Compound Characterization and Structural Analysis; Quin, L. D., Verkade, J . G., Eds.; VCH Publishers: New York, 1994: pp 41-53. (c) Bentrude, W. G.; Setzer, W. N. In Phosphorus-31 Spectroscopy in Stereochemical Analysis; Verkade, J. G., Quin, L. D., Eds.; VCH Publishers: Deerfield Beach, FL, 1987;pp 365-389. (d) Maryanoff, B. E.; Hutchins, R. 0.; Maryanoff, C. A. Top. Stereochem. 1979,11, 187-317. (2)Huang, Y.; Arif, A. M.; Bentrude, W. G. J. Org. Chem. 1993,58, 6235-6246. (3)Nifant'ev, E. E.; Borisenko, A. B.; Sorokina, S. F.; Grachev, M. K.; Zavalishina, A. I. Zh. Obshch. Khim. 1977,47,2474-2480. @
(4) (a) Setzer, W. N.; Sopchik, A. E.; Bentrude, W. G . J. Am. Chem.
SOC. 1985,107,2083-2091. (b) Bentrude, W. G.; Day, R. 0.;Holmes, J. M.; Quin, G. S.; Setzer, W. N.; Sopchik, A. E.; Holmes, R. R. Ibid., 1984,106,106-111.(c) Bajwa, G.S.; Chandrasekaran, S.; Hargis, J. H.; Sopchik, A. E.; Blatter, D.; Bentrude, W. G. Ibid., 1982,104,63856392. (5)(a) Kirby, A. J . The Anomeric Efect and Related Stereoelectronic Effects a t Oxygen; Springer-Verlag: West Berlin, 1983.(b) Juaristi, E.; Cuevas, G. Tetrahedron 1992,48,5019-5087.(c) For applications to six-membered rings see especially: Juaristi, E. Introduction to Stereochemistry and Conformational Analysis; Wiley-Interscience: New York, 1991;Chapters 17 and 18.(d) Juaristi, E.; Cuevas, G. The Anomeric Efect; CRC Press, Inc.: Boca Raton, FL, 1994.
0022-3263/95/1960-4767$09.00/0 0 1995 American Chemical Society
Huang et al.
4768 J . Org. Chem., Vol. 60, No. 15, 1995
Scheme 1
Me
measured coupling constants (Table 11, was demonstrated for all ring protons of 5 and for certain ring protons of 7 and 9. The conformational analyses of the six-membered rings were based on the values of 3 J p and ~ 3 ~ ~J ~Coupling ~ ~ ~ constants 3 J p have ~ ~ not ~ been found to be useful in conformational analyses of three-coordinate phosphorus containing heterocyclic six-membered ring^,^,^,^ as they depend strongly on the substituent a t N(3). Me
To gain further evidence concerning the role of equatorial -equatorial MezNP/N(3)R repulsions in determining the axial or equatorial preference of the Me2N-P bond, a series of 2-Z-3-methyl-1,3,2-oxazaphosphorinanes, 1-9, has been examined. Indeed, all compounds with Z =
Me
1 R, 2 A, 3 R, 4 R, 5 R, 6 R, 7 R1 8 R, 9 R,
-- -- --- - - - -- -- -- -- --
R, Me, Z Me0 R, Me, 2 (CF,),CHO Hy. R,- Hx, 2 MeO Hy, R, Hx, 2 (CF,),CHO R, Me, 2 Me2N Hy, R, Hx, 2 Me2N f.Bu. R2 Hx, 2 -MeO f-Bu. R, Hx, 2 (CF&CHO t-Bu, R, Hx, 2 Me2N
MezN displayed a marked preference for the MezN to be equatorial. This finding is taken to reflect the reduced equatorial-equatorial repulsions for the pair MezNP/ N(3)Me compared to the pair MezNP/N(3)-i-Pr (B) or MeZNPlN(3)Ph (A) that results from the reduced size of the NMe substituent. This research confirms yet another of the remarkable influences of steric and stereoelectronic influences on heteroatom-containing six-membered rings.
Results Preparations. The synthetic route to 3-methyl-1,3,2oxazaphosphorinanes 1-9 is shown in Scheme 1. The kinetic product trans-7 (relation of tert-butyl to RO or MezN)was prepared by a published procedure2 in a trans/ cis ratio of 87/13 (31Pand lH NMR) and converted on distillation to the thermodynamically more stable cis-7. Compound 9 was isolated by distillation as a 40/60 cis/ trans mixture of diastereomers (31PNMR) which slowly changed to a stable, presumably equilibrium, value of 47/ 53 (cis/trans) a t room temperature in C&. Distilled 8 was a t least 95% the cis isomer. IH NMR Parameters and Conformations of 1-9. The pertinent lH NMR coupling constants and chemical shifts for 1-9 are listed in Tables 1 and 2. Protons on the six-membered ring are designated HA, HB, Hc, HD, Hx, and Hy, as shown in 10. For the 5,5-dimethyl compounds (1, 2, and 51, HX and HY are replaced by methyl groups. In cis-7, -8, -9, Hy has been replaced by the tert-butyl substituent, while the tert-butyl replaces HXin trans-9. The NMR data for trans-7 were obtained before purification. Compound 9 was examined as a solution containing both cis and trans diastereomers. Spectra were analyzed on a first order basis. Those for compounds 6 and 9 were also iteratively refined (LAOCN5). The IH NMR signals for cis-9 and trans-9 were poorly separated in C& but well-resolved in CD3CN. The lack of influence of solvent on conformational equilibria, as seen in the relative constancy of
10
11
The data observed for 1-4, cis-7, and cis-8, (Z = Me0 and (CF3)2CHO) are similar to those seen for previously studied three-coordinate 1,3,2-dioxa- and oxazaphosphorinanes that populate chair conformations analogous to 10 with substituents attached axially to phosphorus. Thus, the small values of 3 J (3.8-4.2 ~ Hz), 3 J (3.8~ ~ 4.5 Hz), and 3 J (3.9-4.5 ~ ~ Hz) recorded (Table 1) are characteristic of gauche HCCH and HCOP arrangements, while the large values of 3 J (11.7-13.1 ~ ~ Hz), 3 J (11.6~ 12.5 Hz), and 3 J (11.6-12.5 ~ ~ Hz) observed are typical of antiperiplanar HCCH and HCOP geometries. The relatively large long-range W-configuration couplings recorded, 4 J (-1.4 ~ ~ to -2.3 Hz), also support the assignment of chair conformation 10 to 1-4, cis-7, and cis-8. By contrast, the data recorded for 5 and 6 demonstrate the presence of a chair-chair equilibrium in solution with conformer 11(Z = MezN) dominant, as indicated by the relatively large values of J Anoted ~ (-15 Hz). Chair-form 1,3,2-oxaza- and 1,3,2-dioxaphosphorinanes containing three-coordinate phosphorus with Z equatorial, as in 11, typically display J A values ~ of 1921 H z . ~The relatively large values for JBY(8.7 Hz) and JDY(8.5 Hz) also require that 11be the major conformer populated by 6 (see below for estimates of the populations of 10 and 11). cis-9 (Z = Me2N, HY = tert-butyl) displays a coupling pattern similar to that for cis-7 and cis-8 which were assigned above to the chair conformation 10 (Z = RO, Hy = tert-butyl). The small increase in J Aand ~ decrease in J B Pmost likely arise from the distortion of the ring (10) that was noted previously in the X-ray crystal structure of 5,5-dimethyl-3-phenyl-2-(dimethylamino)1,3,2-oxazaphosphorinane(A, R1 = RP = Me).2 In the same report,2 values of 5.8 and 11.7 Hz for JAPand JBP, respectively, were estimated for 10 from a Karplus plot of 3 J ~ c o vs p dihedral angle. A very minor depopulation of the chair form by cis-9 to occupy a twisthoat conformation may also be in part responsible for the differences in J A and ~ J B Pbetween cis-9 and its cis-7 and cis-8 counterparts and, along with ring distortion, lead to the observed reductions in J m and J ~ seen x in Table 1 for cis-9. The coupling constants for trans-9 are very similar to those of trans-2-(dimethylamino)-5-tert-butyl-1,3,2-dioxaphosphorinane (JAP= 20.2 Hz, J B P= 2.6 Hz, JAY = 4.2 (6) Hutchins, R. 0.; Maryanoff, B. E.; Albrand, J. P.; Cogne, A,; Gagnaire, D.; Robert, J. B. J . Am. Chem. SOC.1972,94, 9151-9158. (7) Bentrude, W. G.; Tan, H.-W.;Yee, K. C. J.Am. Chem. SOC.1975, 97, 573-582.
.
J. Org. Chem., Vol. 60, No. 15, 1995 4769
Conformational Equilibria
Table 1. Selected lH NMR Coupling Constants (Hz)for 1-9" compd 1 2
solvent
3Jap
3JBP
3
CfiDfi
3.8 4.1 3.8 4.1 14.7 14.5 15.3 4.0 6.7 4.2 6.7 6.2 19.4 19.0
12.3 13.1 11.7 12.4 6.8 6.9 6.0 12.4 5.8 12.8
4.2 4.9 3.9 4.6 11.8 11.6 11.8 3.9 3.4 4.6 4.7 4.5 15.4 15.4
3 4 5 5
6b cis-7 trans-7 cis-8 cis-9 cis-gb trans-9 trans-9
C
11.0
c 4.4
J
~3
~
J
3Jsx
3Jcx
3J~x
12.5 12.5
4.5 4.3
12.5 11.7
4.5 4.7
5.8 11.6
3.1 3.9
6.0 11.6
3.9 3.9
11.6 10.6 11.0
3.8 c 4.5
11.6 9.8 10.1
4.0 c 5.3
4 J ~ c 3J.m
~ 4 5~ BD
8.7 9.6 8.4 12.8 4.3 4.2 4.0 9.1 7.0 10.2 c 7.9 c 2.8
-2.3 -2.2 -1.4 -1.4 -1.6 -1.6 -1.4 -1.9 -1.2 -1.9 c -1.4 -2.2 -2.1
3JBy
3Jcy
3J~y
2.3 2.3
2.3 2.7
3.1 3.4
3.1 3.3
4.0
8.7
4.4
8.5
3.8
8.5
5.8
8.7
4.3 4.5
c 9.7
4.6 4.9
c 10.7
3J~y
*
a At 300 MHz, ambient temperature. Iteratively refined by use of LAOCN5 program: RMS error, 0.164 Hz (6), 0.043 Hz ( 9 ) ;probable error, d 0.014-0.017 Hz (6), 0.005-0.006 Hz ( 9 ) ;J , 0.021-0.030 Hz (61,0.008-0.011 Hz (9). Poorly resolved.
Table 2. Selected lH NMR Chemical Shifts (ppm) for 1-C compd
1 2
3 4 5 5 6 cis-7 trans-7 cis-8 cis-9 cis-9 trans-9 trans-9
solvent
A
B
C
D
3.74 3.79 4.02 3.89 3.60 3.57 4.03 3.99 4.03 3.97 3.89 3.84 4.03 3.99
3.00 3.08 3.50 3.41 3.47 3.45 3.83 3.74 3.63 3.75
2.86 2.73 3.16 2.81 2.80 2.58 3.14 3.04 3.03 2.83 3.03 3.15 2.85 2.96
1.82 1.84 2.32 2.13 2.55 2.34 2.84 2.52 2.55. 2.40 c 2.84 c 2.68
b 3.75
b 3.66
X
Y
1.98 1.71
1.12 1.01
1.84 1.79
1.70 1.97
1.65 1.68 1.69
impart 11-12 Hz values to JBP.Moreover, to have J A ~ as low as the observed 6.7 Hz would require essentially total depopulation of 11 in favor of 10. The observed value for JBP(5.8 Hz), however, is much too low for 10. Predominant population of 10 would also lead to a greater reduction in observed JBYand JDY.The coupling constants obtained are instead more typical of those expected if 11 is predominantly depopulated in favor of approximately equal amounts of rapidly equilibrating twistmoat forms 12 and 13 in which HAand HB (as well as Hc and HD) spend equal time in pseudoequatorial and pseudoaxial positions, leading to similar couplings to phosphorus, JAPand JBP,as observed. The values of JBY
1.81 1.74
" A t 300 MHz, ambient temperature. Cis B and trans A overlapped a t 3.7-3.8 ppm. Overlapped with NMez signal.
Hz, JBY= 10.8 H Z ) . ~The large 19.0 Hz value for JAPis typical of an antiperiplanar HCOP geometry with an axial electron lone pair on p h o s p h o r u ~ .Thus, ~ ~ ~ ~trans-9 ~ primarily populates the chair conformation 11 (Hx = tertbutyl, Z = MezN)with both MezN and tert-butyl equatorial. Notably, however, for trans-9, both JBY(9.7Hz) and Jcy (10.7Hz) are less than the 11-12 Hz values typical of the analogous axial hydrogens of cis-7 and cis-8 (Table 1). This likely signifies a minor depopulation of the chair conformation. The previously investigated trans-5-tert-
I-auc I
12
13
and JDYin 12 and 13, as found, should be diminished somewhat but remain nearly equal. Those of JAY and JCY,as expected, are slightly increased from those for the chair, 11. Population of a minor amount of 10 cannot be excluded.
Chair-Chair Equilibrium Constants for 5 and 6.
The equilibrium constants (K,10 11) for 5 and 6 were estimated from the observed JAPand JBPvalues (Table 1) and assumed values for these coupling constants in butyl-3-phenyl-2-(dimethylamino)-1,3,2-oxazaphosphori- 10 and 11. Thus, it is easily shown that (mole fraction nane populates to a considerable extent boat/twist forms 10 = N(101, mole fraction 11 = N(11)) with tert-butyl pseudoequatorial and MezN pseudoaxiaLZ This suggests that instability in trans chair-form rings N(lOW,(lO) N(llV,(ll) = J,(obsd) in 1,3,2-oxazaphosphorinanesystems is most readily relieved in such twisthoat conformations, as will be N(10)= 1 - N(11) established for trans-7. However, the deviations of the therefore, key coupling constants for trans-9 from those of the chair (11) are not great enough to make an independent, truly definitive assignment of conformation to any minor form populated. For trans-7, the observed data deviate strikingly from those expected for chair-form 11 (Hx = tert-butyl, Z = similarly, MeO). Assuming that JAPshould be on the order 19-20 Hz for trans-7 in conformation 11, the 6.7 Hz value found indicates a strong depopulation of 11. The alternative chair form 10, with Me0 and tert-butyl both axial, would
+
(8) Bentrude, W. G.; Tan, H.-W. J.Am. Chem. Soc. 1973,95,46664675. The coupling constants for 14 are revised values (CsDs) from
spectra taken a t 300 MHz and iteratively refined by the LAOCN5 program fY. Huang, unpublished results).
Assumed values for 10 noted above, estimated for the analogous 3-phenyl compound (JBP= 11.7 Hz, JAP= 5.8 H Z ) ,along ~ with values for 11 from all-chair-form trans2 4 dimethylamino)-5-tert-butyl-l,3,2-dioxaphosphori-
Huang et al.
4770 J. Org. Chem., Vol. 60, No. 15, 1995 Table 3. Selected lSCNMR Parameters for 1 - P J, Hz 67 PPm compd solvent PC4 PC5 PC6 PC' C4 C5 C6 C' 1 C& 5.1 1.2 3.9 29.1 56.9 31.6 67.2 37.5 2 C6D6 5.5
