Selectivity in Organic Group Transfer in Reactions of Mixed Lithium ...
[Reprintedfrom the ,Journalof OrganicChemistry,39, 400(1974).] CopyrightI974by the AmericanChemicalSocietyand reprintedby permissionof the copyrightowner.
Selectivity in Organic Group Transfer in Reactions of Mixed Lithium Diorganocuprates 1 W. Harry
Mandeville
and George M' Whitesidest
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Receiued August 29, 1973 (organo = n-butyl, sec-butyl, terfS o l u t i o n s o b t a i n e d b y m i x i n g 1 e q u i v o f o r g a n o ( l i g a n d ) c o p p e r ( I )r e a g e n t group have butyl, phenyl, and 1-pentynyl) with 1 equiv ofan organolithium reagent having a different organic yields of prodbeen allowed to react with 1-bromopentane, methyl vinyl ketone, and nitrobenzene. The relative and used ucts observed in these reactions of "mixed" lithium diorganocuprates, "RrRzCuLi," are summarized form stable, to infer the relative reactivities of the two organic groups in these complexes. Organic moieties that cuprates unreactive, copper(I) compounds (1-pentynl'I, ferf-butoxyl, aryl) show the smallest reactivity in these that the secand are the most generally useful first components for mixed ate complexes in which it is intended in reactions ond component react preierentially with substrate. However, use of these groups has one drawback complex is group mixed in the organic second the of reactivity the reactivity': involving certain substrates of low the corres i g n i f i c a n t l y d e c r e a s e db v i n c l u s i o n i n t h e c o m p l e x , r e l a t i v e t o t h a t w h i c h w o u l d b e e x p e c t e d f r o m insufficient show compounds organocopper stable from made cuprates If mixed cuprate. symmetrical sjonding reactivitl'. mixed complexes containing a highly basic organic group, particularly ferf-butyl, may have advanestablishes t a g e s . A s u r v e y o f t h e r e l a t i v e r e a c t i v i t y o f s e v e r a l a l k y l b r o m i c l e st o w a r d l i t h i u m d i - n - b u t y l c u p r a t e S N 2 r e a c t i o n . o f a n c h a r a c t e r i s t i c c o u p l i n g p r o f i l e f o r n u c l e o p h i l i c a structure-rate
Lithium dialkyl-, diaryl-, and divinylcuprates are wideIy used in organic synthesis.2-aThe most commonly employed preparations of these materials involve reaction between 2 equiv of an organolithium reagent and 1 equiv of copper(I) halide, either alone or complexed with a phosphine, phosphite, or sulfide; the resulting organocopper(I) compound is normally used without isolation (in eq 1, S represents the substrate being attacked by the cup r a t e) . 2RLi +
ICuL
R2CuU'L l-*
RS +
RC\.I, (I)
This procedure suffers from three characteristics that frequently prove inconvenient in practical applications. The first is a consequenceof the low thermal stability and solubility of many uncomplexed organocopper(I) compounds: the 1 or more equiv of trialkylphosphine or phosphite often included in the reaction mixture to stabilize and solubilize the organocopper(I) reagents severely complicates the work-up of the reaction. A second disadvantage of the procedure reflects the stoichiometrv of most of the reactions of lithium dialkylcuprates commonly employed in organic synthesis, ulz., onl.v-one of the two alkyl groups of the dialkSrlcuprate is normallv converted to product; the second, appearing as (unreactive) alk-v-icopper(I) compound, is usually lost to thermal decomposition or in work-up. This circumstance is clearll' unattractive when the starting organolithium reagent is expensiveor difficult to prepare.5 The third is that organolithium reagents are required lor the synthesis; the more readilv available organomagnesium compounds do not always yield organocopper ate complexes having the same reactivitv as lithium dialkylcuprates.6 Two t1'pes o1'partial solutions have been ofl'ered to the problems provided b5' this synthetic procedure. First, trimethy'l phosphiie0b and tris(dimethylamino)phosphine? have been suggested to be more readily separated from products during the work-up of reaction mixtures than are ate complexes, trialkvlphosphines. Second, "mixed" RrRzCuLi, have been prepared b1" mixing 1 equiv o1'an organocopper(I) compound with i equiv of an organolithium compound derived fiom a difl'erent organic moiety: these solutions ma3' show a pronounced and usefui selectivity in transferring one o1'the two organic groups to substrate. Several groups Rr have been used for this purpose: (CHg)gCC:C,e (CH:)sC,6a CN,8 n-CgHzC:C,7 (CH3)sCO.to Of these, the last two appear the most at-
S
R,Cu+R2Li+RrRCuLi RrS +
R,Cu +
R,S +
RCu
(2)
tractive in principle. in major part because (CHe)eCOCu and (CHs)3CC:CCu are both thermally stable and soluble in ethereai solvents in the absence of added ligands; thel' are, however, less readily available than CuCN or nC3H7C:CCu. and these latter materials may offer advantages in noncritical applications. The selectivities afforded by mixed dialkvlcuprates are less clear-cut than those by mixed alkyl(alkylethynyl)cuprates, but these also may have use when high reactivity is required (seebelow). In this paper we report the results of a survev of the selectivities exhibited by a number of mixed lithium diorganocuprates in the transfer of their organic moieties to substrates in three t5zpicalreactions of cuprates: nucleop h i l i c c o u p l i n g w i t h 1 - b r o m o p e n t a n e , l l ' 1 2o x i d a t i v e c o u pling using nitrobenzene,12'13and conjugate addition to methyl vinSrl ketone.s These experiments were carried out in order to establish the most generally useful of the groups Rr (eq 2) in encouraging transfer of the group Rz to substrate, to define the selectivities expected from various combinations of organic moieties, and to explore the possibility tirat the selectivities exhibited in reactions of mixed cuprates might be helpful in inferring their struct u r e si n s o l u t i o n . l a Results Reactions of Mixed Lithium Diorganocuprates with l-Bromopentane. With the exceptions of cuprates containing acet-"-lenicgroups, organocopper reagents were prepared at -78' in tetrahydrofuran solution by addition of' 1 equiv of' one organolithium reagent to 1 equiv of t e t r a k i s I i o d o ( t r i - n - b u t y l p h o s p h i n e ) c o p p e r ( I ) ]f'o l l o w e d b y addition of I equiv of a second organolithium reagent. The I R.l,i
1/.1[CuPRu,]*;ilil
"R'R"('uLi'/
('ll ,Br'
+
R , C , , H ,+j R r C . , H i r ( 3 ) resulting homogeneous solutions of organocopper(I) reagents will be referred tcl fbr convenience simply as solutions of lithium diorganocuprates, "RrRzCuLi," although they probably contain mixtures of several different cuprates and almost certainly incorporate tri-n-butylphosphine and lithium iodide into certain of these species. These solutions were treated with 1 equiv of 1-bromopen-
Mixed Lithium Diorganocuprates
J. Org.Chem.,Vol. 39,No.3, 1974 401
Table I Yields of Coupled Products RrCsHrr and R.:CsfIrr frorn Reaction of Mixed Lithiurn Diorganocuprates "RrR.:CuLi" with 1-Brornopentane -Yield,
Rr
n-CnHn
sec-CaHo
t-C4H,)
CuHt
Rt
n-CqHg sec-CrHc f-CaHl CuH; CrHzC:C sec-CnFf g t-CaHc CuHt CeHzC:C /-CaHo CeHt Ci}HIC:C CuHt CaHzC:C
Registry
no.
o/cQ
RrCoHrr
24406-16-4 49585-84-4 49585-85-5 49585-86-6 39697-41-1 23402-73-5 49585-88-8 49585-89-9 49585-90-2 23402-75-7 49585-91-3 39697-42-2 23402-69-9 49585-93-5
R:CrHu
93 23, 45b 26,33b 84,62b 79,82b
65, 16b 64,96 7, \8b
Selectivity in Organic Group Transfer in Reactions of Mixed Lithium Diorganocuprates 1 W. Harry
Mandeville
and George M' Whitesidest
Department of Chemistry, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139 Receiued August 29, 1973 (organo = n-butyl, sec-butyl, terfS o l u t i o n s o b t a i n e d b y m i x i n g 1 e q u i v o f o r g a n o ( l i g a n d ) c o p p e r ( I )r e a g e n t group have butyl, phenyl, and 1-pentynyl) with 1 equiv ofan organolithium reagent having a different organic yields of prodbeen allowed to react with 1-bromopentane, methyl vinyl ketone, and nitrobenzene. The relative and used ucts observed in these reactions of "mixed" lithium diorganocuprates, "RrRzCuLi," are summarized form stable, to infer the relative reactivities of the two organic groups in these complexes. Organic moieties that cuprates unreactive, copper(I) compounds (1-pentynl'I, ferf-butoxyl, aryl) show the smallest reactivity in these that the secand are the most generally useful first components for mixed ate complexes in which it is intended in reactions ond component react preierentially with substrate. However, use of these groups has one drawback complex is group mixed in the organic second the of reactivity the reactivity': involving certain substrates of low the corres i g n i f i c a n t l y d e c r e a s e db v i n c l u s i o n i n t h e c o m p l e x , r e l a t i v e t o t h a t w h i c h w o u l d b e e x p e c t e d f r o m insufficient show compounds organocopper stable from made cuprates If mixed cuprate. symmetrical sjonding reactivitl'. mixed complexes containing a highly basic organic group, particularly ferf-butyl, may have advanestablishes t a g e s . A s u r v e y o f t h e r e l a t i v e r e a c t i v i t y o f s e v e r a l a l k y l b r o m i c l e st o w a r d l i t h i u m d i - n - b u t y l c u p r a t e S N 2 r e a c t i o n . o f a n c h a r a c t e r i s t i c c o u p l i n g p r o f i l e f o r n u c l e o p h i l i c a structure-rate
Lithium dialkyl-, diaryl-, and divinylcuprates are wideIy used in organic synthesis.2-aThe most commonly employed preparations of these materials involve reaction between 2 equiv of an organolithium reagent and 1 equiv of copper(I) halide, either alone or complexed with a phosphine, phosphite, or sulfide; the resulting organocopper(I) compound is normally used without isolation (in eq 1, S represents the substrate being attacked by the cup r a t e) . 2RLi +
ICuL
R2CuU'L l-*
RS +
RC\.I, (I)
This procedure suffers from three characteristics that frequently prove inconvenient in practical applications. The first is a consequenceof the low thermal stability and solubility of many uncomplexed organocopper(I) compounds: the 1 or more equiv of trialkylphosphine or phosphite often included in the reaction mixture to stabilize and solubilize the organocopper(I) reagents severely complicates the work-up of the reaction. A second disadvantage of the procedure reflects the stoichiometrv of most of the reactions of lithium dialkylcuprates commonly employed in organic synthesis, ulz., onl.v-one of the two alkyl groups of the dialkSrlcuprate is normallv converted to product; the second, appearing as (unreactive) alk-v-icopper(I) compound, is usually lost to thermal decomposition or in work-up. This circumstance is clearll' unattractive when the starting organolithium reagent is expensiveor difficult to prepare.5 The third is that organolithium reagents are required lor the synthesis; the more readilv available organomagnesium compounds do not always yield organocopper ate complexes having the same reactivitv as lithium dialkylcuprates.6 Two t1'pes o1'partial solutions have been ofl'ered to the problems provided b5' this synthetic procedure. First, trimethy'l phosphiie0b and tris(dimethylamino)phosphine? have been suggested to be more readily separated from products during the work-up of reaction mixtures than are ate complexes, trialkvlphosphines. Second, "mixed" RrRzCuLi, have been prepared b1" mixing 1 equiv o1'an organocopper(I) compound with i equiv of an organolithium compound derived fiom a difl'erent organic moiety: these solutions ma3' show a pronounced and usefui selectivity in transferring one o1'the two organic groups to substrate. Several groups Rr have been used for this purpose: (CHg)gCC:C,e (CH:)sC,6a CN,8 n-CgHzC:C,7 (CH3)sCO.to Of these, the last two appear the most at-
S
R,Cu+R2Li+RrRCuLi RrS +
R,Cu +
R,S +
RCu
(2)
tractive in principle. in major part because (CHe)eCOCu and (CHs)3CC:CCu are both thermally stable and soluble in ethereai solvents in the absence of added ligands; thel' are, however, less readily available than CuCN or nC3H7C:CCu. and these latter materials may offer advantages in noncritical applications. The selectivities afforded by mixed dialkvlcuprates are less clear-cut than those by mixed alkyl(alkylethynyl)cuprates, but these also may have use when high reactivity is required (seebelow). In this paper we report the results of a survev of the selectivities exhibited by a number of mixed lithium diorganocuprates in the transfer of their organic moieties to substrates in three t5zpicalreactions of cuprates: nucleop h i l i c c o u p l i n g w i t h 1 - b r o m o p e n t a n e , l l ' 1 2o x i d a t i v e c o u pling using nitrobenzene,12'13and conjugate addition to methyl vinSrl ketone.s These experiments were carried out in order to establish the most generally useful of the groups Rr (eq 2) in encouraging transfer of the group Rz to substrate, to define the selectivities expected from various combinations of organic moieties, and to explore the possibility tirat the selectivities exhibited in reactions of mixed cuprates might be helpful in inferring their struct u r e si n s o l u t i o n . l a Results Reactions of Mixed Lithium Diorganocuprates with l-Bromopentane. With the exceptions of cuprates containing acet-"-lenicgroups, organocopper reagents were prepared at -78' in tetrahydrofuran solution by addition of' 1 equiv of' one organolithium reagent to 1 equiv of t e t r a k i s I i o d o ( t r i - n - b u t y l p h o s p h i n e ) c o p p e r ( I ) ]f'o l l o w e d b y addition of I equiv of a second organolithium reagent. The I R.l,i
1/.1[CuPRu,]*;ilil
"R'R"('uLi'/
('ll ,Br'
+
R , C , , H ,+j R r C . , H i r ( 3 ) resulting homogeneous solutions of organocopper(I) reagents will be referred tcl fbr convenience simply as solutions of lithium diorganocuprates, "RrRzCuLi," although they probably contain mixtures of several different cuprates and almost certainly incorporate tri-n-butylphosphine and lithium iodide into certain of these species. These solutions were treated with 1 equiv of 1-bromopen-
Mixed Lithium Diorganocuprates
J. Org.Chem.,Vol. 39,No.3, 1974 401
Table I Yields of Coupled Products RrCsHrr and R.:CsfIrr frorn Reaction of Mixed Lithiurn Diorganocuprates "RrR.:CuLi" with 1-Brornopentane -Yield,
Rr
n-CnHn
sec-CaHo
t-C4H,)
CuHt
Rt
n-CqHg sec-CrHc f-CaHl CuH; CrHzC:C sec-CnFf g t-CaHc CuHt CeHzC:C /-CaHo CeHt Ci}HIC:C CuHt CaHzC:C
Registry
no.
o/cQ
RrCoHrr
24406-16-4 49585-84-4 49585-85-5 49585-86-6 39697-41-1 23402-73-5 49585-88-8 49585-89-9 49585-90-2 23402-75-7 49585-91-3 39697-42-2 23402-69-9 49585-93-5
R:CrHu
93 23, 45b 26,33b 84,62b 79,82b
65, 16b 64,96 7, \8b
