6457 Table I.
Stereospecific Conversion of Alkynes t o Alkenyl Bromides cia Hydroboration-Bromination-Elimination ~~
~
~
Intermediate brominated (yield.
Temp? ”C
Base used
1-Octyne
Boronic acid (90) Catechol ester (90)
- 20 0
M e 0 Na- M eOH Aq NaOH
99 % CIS 99% CIS
Cyclohexyleth yne
Boronic acid (93) Catechol ester (93) Catechol ester Catechol ester (92) Catechol ester (97)
- 40 - 40 -40 - 20
MeONa-MeOH MeONa-MeOH MeONa-MeOH MeONa-MeOH MeONa-MeOH
9 9 % cis 99% C I S 9 9 % c1s 99 trans 98 7; trans
Z)”
Alkyne
Phen yleth yne 3-Hexyne 4,4-Dimethyl-2-pentyne
- 20
Stereochemical purit)‘
Yield of alkenbl bromide.? y; 94.’ 8 S 90e (91 .d 82e)
95,d 88‘ 91.d 85‘ 90e 92 .I 85. 99.d 96e
a See ref 2. * At higher temperatures the stereochemical purity of the product is lower. The alkenyl bromides were identified and characterized by means of gc, ir, pmr, and mass spectrometry. The stereochemistry of the internal alkenyl bromides was determined by preparation of the lithio derivatives (A. S . Dreiding and R. J. Pratt, J . Amer. Clzem. Soc., 76, 1902 (1954): D. Y . Curtin and J. W. Crump. ihid,. 80, Based on the intermediate boronic acid or its 1922 (1958)), followed by protonolysis and the identification of the resulting olefin by gc. ester. e Based on the alkyne. The yields by isolation are given in parentheses.
base-induced trans elimination of boron and bromine to give the product6 (eq 5).
H ’ -
’B-
\
H‘
In the case of the iodine reaction,’ the interpretation must be less definite at this time. The intermediate undergoing reaction is postulated to be the neutralized boronic acid. It was observed that the vinyl iodide is formed at a rate slower than that at which the iodine disappears. Consequently, the reaction cannot involve a direct electrophilic attack of iodine on the carbon-boron bond. We wish to propose that there is a trans addition of the elements of hypoiodous acid via an iodonium ion intermediate,’ followed by a cis elimination (eq 6 ) .
evident that we are now in a position to convert alkynes into vinyl bromides and iodides of opposite configurations, very conveniently via hydroboration with catecholborane. These vinyl bromides and iodides are readily converted into vinyl Grignardg and vinyllithium’O8 ’’ derivatives with retention of their stereochemistry. Consequently, the present developments open up highly practical routes from the readily available alkynes to these valuable vinyl metallics of known stereochemistry. (9) H. Normant, Adcan. Org. Chem., 2, l(1960). (10) See references in footnote c of Table I. (11) (a) E. J. Corey and D. J. Beames, J . Amer. C h m . Soc., 94, 2710 (1972); (b) A. F. Kluge, N . G . Untch, and J. H . Fried, ibid., 94, 9256 (1972). (12) Visiting scholar on funds provided by Fuji Photo Film Co., Ltd., Tokyo, Japan. (13) Postdoctoral research associate on grants provided by G. D. Searle and Co., Chicago, Ill., and the National Science Foundation (Grant No. 27742X).
Herbert C. Brown,* Tsutomu Hamaoka,’* N. RavindranI3 R icliurd B . Wethe rill Lubn rci t o ry Pirrriirc L’iiirersiry Wost La$ryette. Iiidiuirri 47907 Rrcpicrd July 11. 1973
Determination of the Preferred Conformations Constrained along the C-4’-C-5’ and C-5’-~0-5’ Bonds of P-S’-Nucleotides in Solution. Four-Bond 3iP-1H Coupling’
It was suggested earlier that P-substituted organoborane derivatives undergo cis eliminations preferentially when the substituent is one involving oxygen (alkoxy, acetate, etc.) capable of forming a dative bond from oxygen to boron.6c,8 A number of modifications of this mechanism can be suggested. However, it is preferable to defer more detailed consideration until such a time as more mechanistic data become available. Irrespective of the precise mechanism involved, it is
Sir: The Newman projections 1-111 and IV-VI respectively illustrate the preferred conformations constrained along the C-4’-C-5’ and C-5’-0-5’ bonds of a $-5’-nucleotide. An important stereochemical consequence of a @-5’-nucleotide existing in the gg-g’g’ ( I and I V ) conformation is that the atoms H-4’, C-4’, C-5’. 0 - 5 ’ , and P-5’ are in the same plane and that the four bond coupling path between H-4’ and P is the familiar “W” (VII). When the molecule is rotated into arzj’ other conformation this W relationship is destroyed. Studies by Hall, et u I . , ~ - ~indicate that the magnitude of
(6) (a) D. S . Matteson and J. D. Liedtke, J . Amer. Chem. Soc., 87, 1526 (1965); (b) H. C. Brown, D. H. Bowman, S . Misumi, and M. IC. Unni, ibid., 89,4531 (1967); (c) D. J. Pasto and Sr. R . Snyder, 0. S . F., J. Ora. Chem., 31,2773 (1966). (7) (a) G. Zweifel, H. Arzoumanian, and C. C. Whitney, J . Amer. Chem. Soc., 89, 3652 (1967); (b) G. Zweifel, N. L. Polston, and C. C. Whitney, ibid., 90, 6243 (1968). ( 8 ) (a) H.C. Brown and E. F. Knights, ibid., 90, 4439 (1968); (b) H. C. Brown and 0. J. Cope, ibid., 86, 1801 (1964); (c) H . C. Brown and R. M. Gallivan, Jr., ibid., 90,2902 (1968).
(1) This research was supported by the grants from the Nntional Cancer Institute of the National Institutes of Health (CA12462-03), the National Science Foundation (B028015-001, GB28015, GP28061), the National Research Council of Canada (AG434), and the Research Corporation of New York. We thank Dr. Arthur A . Grey, Canadian 220-MHz NMR Center, Sheriden Park, Ontario, Canada, for the 220MHz nmr spectra. (2) L. D. Hall and R. B. Malcolm, Can. J . Chem., 50, 2092 (1972). (3) L. D. Hall and R . B. Malcolm, Can. J . Chem., 50, 2102 (1972). (4) B. Donaldson and L. D. Hall, Cmz. J . Chem., 50, 21.1 1 (1972).
Communications to the Editor.
6458
a 06azaUMP
\
1GALICHE GAUCHE$ [GAUCHE-TRPNSI (TRANS G A U C K f
70 6.0-
-
- 83
VI
9.0
90 4.0-
8.0-
“lo HZ
HZ
100 3.0 -
\ -
7.0 I
I
I
I
I
I
1
1
1
I
I
I
I
I
I
‘TP4#
1
1
,
1
1
1
1
1
1
,
,
,
1
1
1
1
0.0 0.4 0.8 12 1.6 2.0 2 4 28
12 1.6 20 24 28
0.0 0.4 08
“Jp4, Hz
Hz
Plot
4J1~--rlp coupling in W-oriented HCCOP fragments of phosphate esters exhibits a maximum value of -2.7 Hz and suggest a reduction to -0.0 Hz when this relationship is absent. As a logical extension we may postulate that 4 J ~ . 4will f reflect the conformational preferences about C-4’-C-5’ and C-5’-0-5‘ bonds and in particular reflect the extent of planarity (i.e., the gg-g’g’ orientation) of the H-4’-C-4’-C-5’-0-5 ’-P-5’ fragments of p-5 ’-nucleotides. To unravel the interrelationships between the conformers constrained to C-4’-C-5’ and C-5’-0-5’ and 4J~.4~ we have determined5t6 3 J 4 ~ 5 7 3J4t5tt(Z), 3 J ~ . 5 f t ( Z ’ )and , 4J~.41 for the 14 nucleotides in l J certain Figure 1. Other investigators have seen 4 J ~ . in nucleotide^.^-^ From the sums Z and Z’, the fractional populations of gg (P,,) and g(g’ ( P g J gwere f ) computed using expressions 1 and 2 developed earlier.1°-13 In
+
t9’
V
-- 7 2 - 7 8 10.0 -
-
Figure
0
lV
+
3 J ~ - ~ 1
( 5 ) Spectra of the nucleotides, commercial preparations, 0.1 M , pD 8.0, 30’ in 100yo Dz0, were obtained in a 220-MHz nmr system or a lOO-MHz, fast Fourier transform system using a 16K transform in 1H and ‘H- { alp] modes. Details of the instrumentation are discussed elsewhere.6 Computer-simulated (LAME) spectra were generated as a final test of the derived data, In molecules in which the 4Jp.4, is small (1.0 Hz, the predominant conformer is ggg'g', whereas if 4J~-4f is small (
