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Control of the Relative Electrophilicity of Alkylating Agents by Variation of the Lewis Acid Concentration.

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Table I . Carbosulfenylation of allyl ethers 20 [a].
R'
R'
CHI
CH,
CH,Ph
CH2Ph
SiMe,
SiMe,
SitBuPh:
SitBuPh.
SitBuMe,
SitBuMe,
CH,
CH,
CH,
CH,
CH,
CH,
CHI
CH,
CH,
CH,
CH,
CIH~
Ti"C1
Yield [%]
23 : 24
50
50
60
61
69
70
77
77
70
72
40
99: 1
94: 6
85 : I5
74 : 26
84 : 16
60 : 40
60 : 40
50 : 50
47 : 53
32 : 68
99: I
0
- 78
0
- 78
0
-78
0
- 78
0
- 78
0
[a] The carbosulfenylation was carried out at the given temperatures, the methylation immediately thereafter with (CH1)2Zn/TiClaat O"C-Z2"C/15 h.
the positive sulfur atom and the electron-rich oxygen residue has a stabilizing effect.["1 Consistent with this hypothesis is the significantly smaller 1,2-asymmetric induction
with larger protective groups which hinder this interaction.
The influence of the temperature of the PhSCl addition o n
the stereochemistry of the subsequent methylation points
to a possible equilibration of diastereomeric p-chlorosulfides." 'I The diastereoselectivity can even be reversed with
the tert-butyldimethylsilyl protective group. The results are
preparatively important, since the interplay of 1,2-asymmetric induction and trans-stereospecificity leads to a welldefined 1,3-~tereorelation.[~~
Preliminary experiments with further organometallic
reagents as well as other arylsulfenyl chlorides can be summarized as follows: ethyl moieties can be stereospecifically
introduced with AlEt, (e.g. 2b-+ 25).
0YPh 0"'
Etdl
-zzzGx+
2b
"SPh
25 (85%)
Organoaluminum reagents are less suited for ally1 ethers, since, inter alia, ether cleavages occur. Cuprates such
as (CH3)2CuLi d o not effect methylation. Replacement of
PhSCl by 2,4,6-triisopropylphenylsulfenyl chloride leads
to adducts which afford fewer by-products with (CH,),Zn/
Tic&(starting olefins/CH,SPh). For example, the adduct
of cyclohexene can be methylated to the extent of 90%
(82% isolated, in contrast to 68% in the case of 4b). The
bulky residue on the sulfur suppresses the undesired thiophilic attack. It remains to be seen whether these steric effects also influence regio- and stereoselectivity!"]
the known trans-1,3-dimethylcyclohexane.The assignment of the compounds 23/24 was achieved as follows: after removal of the protective
group on the oxygen, the sulfur residue was methylated with
(CH3)30BF, and an epoxide was formed stereospecifically (23 gave the
cis-epoxide, 24 the trans-isomer).
[S] W. A. Smit, N. S. Zefirov, I. V. Bodrikov, M. Z. Krimer, Acc. Chem. Res.
12 (1979) 282; E. Kiihle, Synfhesis 1971. 617.
[9] Electrophilic additions to chiral olefins with electronegative substituents
at the ally1 position proceed stereochemically differently depending o n
the electrophile and substrate. For a survey of the literature on this
theme as well as an attempted explanation [lo] see: S. D. Kahn, W. H.
Hehre, J. Am. Chem. SOC 109 (1987) 666.
[lo] Alternative theories: K. N. Houk, S. R. Moses, Y.-D. Wu, N. G. Rondan, V. Jager, R. Schoke, F. R. Fronczek, J. Am. Chem. SOC.106 (1984)
3880; K. N. Houk, M. N. Paddon-Row, N. G. Rondan, Y. D. Wu, F. K.
Brown, D. C. Spellmeyer, J. T. Metz, Y. Li, R. J. Loncharid, Science 231
(1986) 1108.
[ I l l Of course, 22 can also assume a conformation in which the alkoxy
group is situated near the sulfur residue; this would, however, cause an
unfavorable steric interaction between the methyl group and the threemembered ring. Use of the Hehre model in which the entering electrophile is guided by the alkoxy residue (91 would require a kinetically controlled reaction.
1121 Typical procedure: Phenylsulfenyl chloride (2.9 g, 20 mmol) is added at
0°C (or -78°C) (see Table I ) to a solution of cyclohexene ( 2 mL,
20 mmol) in anhydrous CH2C12under argon until a permanantly paleyellow colored solution is obtained (quantitative conversion). After
10 min, 5 mL of a 4 M (CH3)2Zn-solution in CHICl2 (1.9 g; 20 mmol of
pure (CH3)2Zn) is syringed into the stirred reaction solution at 0°C.
Upon subsequent addition of TiCI, (0.44 mL. 4 mmol) the solution turns
blood red. Thereafter the solution is stirred for IS h at room temperature. The black-brown mixture is poured into 100 mL of ice-water,
treated with 2 N HCI to dissolve any precipitate, and the aqueous phase
extracted several times with ether. The combined organic phases are
washed with NaHCO, and NaCl solutions and dried over MgSO,. After
removal of the solvent the residue is distilled in a Kugelrohr (80-82"CIl
torr). Yield: 2.7 g (68%) of pure 4b. The same procedure using 2.4.6triisopropylsulfenyl yields, after column chromatographic purification.
82% of the analogous product
Control of the Relative Electrophilicity of
Alkylating Agents by Variation of the
Lewis Acid Concentration**
By Herbert Mayr*. Christian Schade, Monika Rubow,
and Reinhard Schneider
Dedicated to Professor George A. Olah on the occasion
of his 60th birthday
The Lewis acid-catalyzed addition of alkyl halides 1 to
alkenes 2 represents a straightforward method for the formation of CC-bonds.
/
1
R-X
+
,C=C,
Lewts
I
1
R-C-C-X
I
1
2
I
3
Received: May 25, 1987 [ Z 2258 IE]
German version: Angew. Chem. 99 (1987) 1081
[ I ] M. T. Reetz: Organotitanium Reagents in Organic Synrhesis, Springer,
Berlin 1986.
[Z] M. T. Reetz, J. Westermann, R. Steinbach, Angew. Chem. 92 (1980) 933;
Angew Chem. fnt. Ed. Engl. 19 (1980) 901.
131 For a review of the a-alkylation of carbonyl compounds with SNl-active
alkylating agents: M. 7. Reetz, Angew. Chem. 94 (1982) 97; Angew.
Chem. Inr. Ed. Engl. 21 (1982) 96.
141 G. H. Posner, T P. Koga, J. Chem. SOC.Chem. Commun. 1983. 1481.
[S] M. T. Reetz. M. Sauerwald, P. Walz, Tetrahedron Left. 22 (1981) 1101.
[6] For the carbosulfenylation of olefins with introduction of cyano groups
see: B. M. Trost, M. Preckel, L. M. Leichter, J.Am. Chem. SOC.97(1975)
2224, and for those with introduction of enolates and allyl moieties see:
M. A. Ibraginov, W. A. Smit, Tetrahedron Lert. 24 (1983) 961; R. P. Alexander, l. Paterson, ibid. 24 (1983) 591 l).
[7] The trans arrangement in 4 was demonstrated ' H - N M R spectroscopically. In the case of 19. desulfurization (Raney nickel) led exclusively to
Angen. Chem I n / . Ed. Engl. 26 (1987) No. 10
When only small equilibrium concentrations of carbenium ions are generated during such reactions, the selective formation of 1 : 1 products can only be achieved if the
reactants 1 ionize faster than the products 3."l Other regularities result when the condition AGO (ionization) % 0 is
abandoned, and the foregoing rule turns out to be a special
case of a more general principle.'" We now demonstrate
[*] Prof. Dr. H. Mayr. DipLChem. C. Schade, M. Rubow,
[**I
Dipl.-Chem. R. Schneider
lnstitut fur Chemie der Medizinischen Universitgt
Ratzeburger Allee 160, D-2400 Liibeck 1 (FRG)
This work was supported by the Deutsche Forschungsgemeinschaft and
the Fonds der Chemischen Industrie. C. S . thanks the Stiftung Volkswagenwerk for a Kekule fellowship.
0 VCH Verlagrge.~elIschaftmbH, 0-6940 Weinheim, 1987
0570-0833/87/1010-109 $ 02.50/0
1029
for a model reaction, how to invert the relative reactivities
of alkylating agents by varying the concentration of the Lewis acid (see Scheme I).
kre1=5?
-
c
FH3
7
An-CHCI
An-CH-CH2-C-CI
I
la
I
I
Ph
Ph
t
2-1
p/
C3H,
3a
y
0
An-CH
3
An-CH-CH,-C-CI
I
BCk'
I
To1
I
To1
l+b
C3H,
-
3b
L
-1i
\
0.2 equiv. BCI,
Scheme I . An =p-methoxyphenyl, To1 =p-tolyl
When 5 equivalents of BC13 (6.0 mmol) and 0.20 mmol
o f 2-methyl-I-pentene 4 are added successively to a solution of the diarylmethyl chlorides l a (0.40 mmol) and l b
(0.80 mmol) in dichloromethane, the 1 : 1 adducts 3a and
3b are formed in the ratio 2.98 : 1. From this experiment, a
competition constant k,/kb= 7.2 is derived,'31 which is
closely similar to the ratio of the rate constants directly
measured for the reactions of l + a and l + b with 4
(7.06);14' under these conditions both diarylmethyl chlorides are fully ionized.
Reduction of the BCI, concentration causes a decrease
of the reactivity ratio a / b (Fig. l), and a value of 0.18 is
achieved when 0.05 equivalents of BC13 are used. The less
reactive carbenium ion 1+ b now reacts preferentially, because o f its higher concentration in the preceding equilibrium (Curtin Hammett situationfS1).A theoretical value of
0.18 is obtained for the competition constant at low catalyst concentrations by multiplication of the ratio k( 1 +a)/
k ( 1 +b)with the NMR spectroscopically determined equilibrium constant K = ([l +a][lb])/([ la][l +b])= 0.025.
2
4
In this system, the difference between the reactivities of
two electrophiles increases with increasing difference of
the ionization standard free enthalpies (AAG~,i,,,i,,) of
the two competitors. Under conditions of prevailing ionization, the p-phenoxy-substituted benzhydryl cation is
5400 times more reactive than the bis(p-methoxy)-substituted benzhydryl cation, while in presence of catalytic
0 VCH Verlagsgesel1schaJi mbH, 0-6940 Weinheirn, 1987
Fig. 2. Relative reactivity of para-substituted diarylmethyl chlorides towards
2-methyl-I-pentene in presence of catalytic amounts of Lewis Acid (bottom)
and under conditions of complete ionization (top) (CH2Cl2/- 70°C).
amounts of Lewis acid the relative reactivity is 0.016
(Fig. 2).
A situation as described above is generally encountered
in electrophilic alkylations of the type 1 2 - 3 . The 1/1+
and 3/3+ couples compete for the alkene 2, and it depends on the magnitude of the particular competition constant, whether selective formation of 3/3+ or polymerization takes place. Hence the following rules result:
+
A: I f the carbenium ion I + is less stabilized than 3+ [i.e.
AGj)onrzatron
(1) > AGj)o,,,i,,,,,(3)] the selective formation
of I : I products requires at least an equivalent amount of
a completely ionizing Lewis acid.
B: i f the carbenium ion I + is better stabilized than 3+ [i.e.
AG?on,liltion
( I ) < AGr)oniLi,tion
(3)] the I :I products are
formed most selectively with (catalytic amounts 08the
weakest possible Lewis acid.
Received: May 26, 1987 [Z 2261 I€]
German version: Angew. Chem. 99 (1987) 1059
Fig. I . Relative reactivity of the diarylmethyl chlorides lalb towards 2-methyl-I-pentene in CH2C12at - 70°C as a function of the Lewis acid concentration.
1030
AAG"[ionizationl-
Since AHo (=AGo+const.) of the ionization of alkyl
chlorides and AG' of the corresponding solvolysis reactions are proportional to each other,I6' rule B is equivalent
to the earlier alkylation rules,lla.blwhich were restricted to
systems with a small degree of ionization. These rules have
proven useful in the case of electrophilic carboxylations
and carbonylations of alkenes""' and for a new cyclopropene-cyclopropenone synthesis by addition of trichloropropenylium ions to 01efins.1'~~
- I /
I
\
krel=O.O16
-2
[I] a) H. Mayr, Angew. Chem. 93 (1981) 202; Angew. Chern Int. Ed. Engl 20
(1981) 184; b) H . Mayr, W. Striepe, J . Org. Chem. 48 (1983) 1159; c) H.
Mayr, H. Klein, G. Kolberg, Chem. Ber 117 (1984) 2555.
[2] H. Mayr, R. Schneider, R. Pock, Makrornoi. Chem. Macromol. Symp. 3
(1986) 19.
[3] a) R. Huisgen: Ausfuhrung kinetischer Versuche in Houben- Weyl. Methoden der Organischen Chemie. Band I I I / I . Thieme, Stuttgart 1970, p. 144;
b) C . K. Ingold, F. R. Shaw, J . Chem. Soc. 1949. 575.
141 R. Schneider, U. Grabis, H. Mayr, Angew. Chem. 98 (1986) 94; Angew.
Chem. Int. Ed. Engl. 25 (1986) 89.
[ 5 ] a) D. Y. Curtin, Rec. Chem. Progr. I5 (1954) 11 I ; b) L. P. Hammett: Physic51 Organic Chemistry, McGraw-Hill, New York 1970; c) J. 1. Seeman,
Chem. Reu. 83 (1983) 83.
161 E. M. Arnett, C . Petro, P. van R. Schleyer, J . Am. Chem. Soc. I01 (1979) 522.
171 a) H. Mayr, M. van der Briiggen, Chem. Ber., in press; b) K. Musigmann,
H. Mayr, A. d e Meijere, Tetrahedron Lett. 28 (1987) 4517.
0570-0833/87/1010-l030$ 02.50/0
Angew. Chem. Int. Ed. Engl. 26 (1987) No. I0
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