FORMATION AKD ALKYLATION OF LITHIUM ENOLATES
J . Oyg. Chenz., Vol. 37, N o . 24, 1972 3873
Formation and Alkylation of Lithium Enolates from Enol Phosphorylated Species' IRVING J. BOROWITZ,** EDWARD W. R. CASPER,ROSALIE K. CROUCH, AND KWOKCHUNYEE Department of Chemistry, Beljer Graduate School of Science, Yeshiva University, New York, X e w York
10033
Received M a y 10, 1972 The cleavage of vinyl phosphinates, vinyl phosphonates, or vinyl phosphates, derived from cyclic a-halo ketones, with methyl- or butyllithium smoothly yields the corresponding lithium enolate and inert phosphoruscontaining by-products. Cleavage of enol triphenylphosphonium halides occurs but is complicated by the formation of biphenyl and triphenylphosphine as by-products and by the hydrolytic instability of the starting compounds. The lithium enolates thus formed can be regiospecifically monoalkylated on carbon in good yield. Polyalkylation occurs as a minor process mainly in methylation and is negligible for larger alkyl groups. Alkylation of several enolates, formed from ketones with lithium triphenylmethide, gives comparable results. A notable exception to the regiospecificity of the alkylations occurs with the less substituted lithium enolate of 2-methylcyclohexanone, which gives 2-methyl-2-butylcyclohexanone and not the desired 2-methyl-6-butylcyclohexanone. Corresponding methylation gives 2,6-diniethylcyclohexanone. The cleavage and alkylation of derivatives of acetone and butyraldehyde are described. The preparation of 2-methyl-6-bromocyclohexanone is discussed.
The conversion of a-halo lietones to vinyl phosphates occurs smoothly in high ~ i e l d . ~Vinyl , ~ phosphinates and phosphonates are also available from the reactions of a-halo ketones with alkyl diphenylphosphinites and dialkyl phenylphosphonite~.~Less generally, some halo lietones can be converted to enol triphenylphosphonium salts upon reaction with triphenylphosphine (TPP).6 This procedure avoids obtaining mixtures of the two possible enol derivatives of an unsymmetrical ketone as sometimes found in the formation of enol acetates' or enol trimethylsilyl ethers.*r9
1
1
Grignard reagents to give ketones.12 We now report the successful utilization of enol phosphorylated species along these lines.13
Results and Discussion Our initial results involved the cleavage of enolphosphorylated derivatives of the 1,2-diphenylethylene system (Table I) .Ir-ith phenylmagnesium bromide or phenyllithium. The enol triphenylphosphonium chloride 6 , from a-chlorobenzyl phenyl ketone (2) and TPP,6d reacts with phenylmagnesium bromidc or phenyllithium to give the enolate 7. Biphenyl and TPP, formed as by-products, may arise via tetraphenylphosphonium halide and pentaphenylph~sphorane'~ intermediates, as postulated in P-lietophosphonium salt reactions with Grignard reagents.'*
11
Ph ,PO
n "
OPPhj
cleaved by strong bases to give lithium or magnesium enolates, which could then be m o n ~ a l k y l a t e d . ~ ~ ~ ~ II I The idea was originally based on the in vivo reactions of Pht-bPh phosphoenol pyruvate with carbon dioxide"" or with sugar aldehydes,"b and more recently on the cleavage I of a,a-disubstituted p-ltetophosphonium salt's wit'h
I
I
5
4
PPh,
y+ph'
PhC =CHPh 6
3, X - B r
-
9-M'
PhMgBr
PhC=CHPh
\ 2, X = C l
(1) This investigation mas supported by Grant KO, 19,664 from the National Science Foundation. This is part 22 of the series Organophosphorus Chemistry. Taken in part from R . K . Crouch, Ph.D. Thesis, Yeshiva University, 1972. Presented in part a t the Heteroatom Chemistry Meeting, London, Ontario, Sept 1970. (2) T o whom correspondence should be addressed. (3) (a) F. W.Lichtenthaler, Chem. Rev., 61,607 (1961); (b) P. A. Chopard, V. M. Clark, R. F. Hudson, and A . J. Kirby, Tetrahedron, 31, 1961 (1965). (4) (a) I . J. Boromitz, M. Anschel, and S. Firstenberg, J . Org. Chem., 82, 1723 (1967); (b) I . J. Borowitz, S. Firstenberg, E. W.R . Casper, a n d R . K. Crouch, ibid., 86, 3282 (1971). (5) I. J. Borowitz and R . K. Crouch, Phosphorus, in press. (6) (a) I. J . Borowitz, K . Kirby, P. E . Rusek, and E. W. R . Casper, J . Org. Chem., 86, 88 (1971); (b) A. J. Speziale and R. D. Partos, J . Amer. Chem. Soc., 86, 3312 (1963); (0) R . D. Partos and A. J. Speeiale, i b i d . , 87, 5068 (1965); (d) I. J. Borowitz, P . E. Rusek, and R . Virkhaus, J . 01.g. Chem., 3 4 , 1.595 (1969). (7) (a) 13. 0. House and B. M. Trost, ihid., 30, 1341, 2502 (1965); (b) H. 0 . House, Rec. Chem. Progr.. 28, 99 (1967); (c) H . 0. House and C. J. Blankley, J . Oro. Chem., 83, 1741 (1967); (d) H . 0. House and T. M~ Bare, ihid., 83, 943 (1968). (8) G. Stork and P. F. Hudrlik, J . AmeT. Chem. Soc., 90, 4462, 4464 (1968). (9) H . 0. House, L. J. Czuba, M . Gall, a n d H. 0. Olmstead, J . O w . Chem., 34, 2324 (1969). (10) H. 0. House, M . Gall, and H. 0. Olmstead, ihid., 36, 2361 (1971). (11) (a) J. L. Graves, B. Vennesland, M . F. Utter, and R. J. Pennington, J . B i d . Chem., 223, 551 (1956); (b) P . R . Srinivasan and D. B. Sprinson, ibid., 284, 716 (1959).
+
I
It was felt that enol phosphorylated species should be
or PhLi
PhMgBr
Phk=CHPh 7a, >I = ~1 b, M = M g B r
,/
4CH I
O
H
1I I
PhC -CPh
I
R 8, R = H 9. R = C H ,
The enol phosphonium bromide 11, derived from 10, reacted similarly. 0
OP +Ph8Br-
II
PPhs
I
PhCCPh2 +PhC=CPh*
I
Br 10
PhMgRr
-+
11
0-MgBr
I
+
CHd
PhC=CPhz 12
O R 11 1 PhC-CPhz 13, R = H 14, R = CHI
(12) T. Mukaiyama, R . Yoda, and I. Kuwaijima, Tetrahedron Lett., 23 (1969). (13) I. J. Boromitz, E. W.R. Casper, and R. K. Crouch, i b i d . , 105 (1971). (14) (a) G. Wittig and G. Geissler, Justus Liebigs A n n . Chem., 580, 44 (1953); (b) G. Wittig and M. Rieber, i h i d . , 662, 187 (1949).
3874 J . Org. Chem., Vot. 37, No. 24, 1978
BOROWITZ, CASPER,CROUCH, AA-D YEE
TABLE I CLEAVAGE AND SUBSEQUENT REACTIONS OF PHOSPHORYLATED DIPHENYLETHY ETHYLENES
---
r
Compd
Conditions
Methyl ketone
Ketone
OR
11
----_
Yield, %Biphenyl
OPPhr
PPha
PhMgBr,. THFb 1 36 16 100 CHsI addedb 6 PhLi, THFb 4 86 64 100 CHsI addedc 5 PhMgBr,. THFb 1 85 98 2. CHaI addedb 11 1. PhMgBr, T H F (25") 27 46 34d 99 2. CH31 added, 2j0, 16 hr a Two equivalents. Reflux 12 hr. Reflux 5 hr. From the acidification of the enolate in a separate experiment. Oxidation of anticipated PPh, may have occurred during work-up. 1. 2. 1. 2. 1.
6
TABLE I1 CLEAVAGE-ALliYLATION O F CYCLOPENTENYL DERIVATIVES WITH METHYLI 0 D I D E a " J -Products-
I
Compd @O(:Ph: 15
Organolithium (1 equiv)
7
Solvent
CH3Li CHsLi
Glyme THF
1 1
n-CdHgLi
Glyme
5
77 ( 7 6 ) ~ 74 (72).
64
7 7
12 15
3 3
16
9
6
16
~ O O , O , , ~
CH,Li Glyme 12 78 4 6 0 17, R = CzHs CH3Li Glyme 14 62 9 12 3 i-C3H7 a Cleavage for 3 min at room temperature; alkylation at 0" and quenched after 1 min. * All samples analyzed by vpc at 110" on 2 0 7 ~SE-30. Retention times: cyclopentanone, 2.3 min; 2-methylcyclopentanone (3.3); 2,2-dimethylcyclopentanone (3.8); 2,sdimethylcyclopentanone (4.3). Yield by vpc calibration curve. 18, R
T.4BLE 111 CLEAVAGE-ALKYLATION OF CYCLOHEXENYL DERIVATIVES WITH METHYL IODIDER-~
Compd
Organolithium (equlv)
CIeavage temp, OC
Solvent
ss
-Products------1
a8
1.6 90.4 (86p 8.0 Glyme-DMSO ( 2 :1 ) 14 81 (80)" 5 CHaLi (1 . O ) 25 Glyme 20, R = Ph, OCdHo 21, R = OC2Ho CH3Li (1.0) 25 Glyme 32 63 1 25 Glyme 13 79 (75)C 8 CH3Li (2.0) 21 22, R = O-i-C,H? CHaLi (1.0) 25 Glyme 12 86 2 Alkylating solutions a t 0" and alkylation step terminated after 5 min. b Ypc conditions for product analysis a Cleavage for 5 min. a t 130' on 2OY0 SE-30. Retention times: cyclohexanone (3.3 min); 2-methylcyclohexanone (4.5); 2,2-dimethylcyclohexanone (5.
