"Activated" Phosphoranes for the Cyclodehydration and Chlorination

33

Downloaded by UNIV OF MARYLAND COLL PARK on October 14, 2014 | http://pubs.acs.org Publication Date: November 11, 1981 | doi: 10.1021/bk-1981-0171.ch033

"Activated"Phosphoranes for the Cyclodehydration and Chlorination of Simple Diols S. WOODY BASS, CAREY N. BARRY, PHILIP L. ROBINSON, and SLAYTON A. EVANS, JR. The William R. Kenan, Jr. Laboratories of Chemistry, The University of North Carolina, Chapel Hill,NC27514

The scope and synthetic utility of dioxyphosphoranes, and particularly, diethoxytriphenylphosphorane (DTPP), as useful cyclodehydrating "reagents" for the conversion of diols to cyclic ethers have received only superficial attention (1). The DTPP-diol -> ether route has several unique advantages over existing methods: (a) the reaction conditions are effectively neutral and mild, (b) the stereoselectivity in the closure of both unsymmetrical and symmetrical diols to cyclic ethers is high, and (c) the isolation of the product(s) from triphenylphosphine oxide (TPPO) is convenient. We have systematically examined the facility with which DTPP promotes the cyclodehydration of simple diols to cyclic ethers: 1,3-propanediol (1) -> oxetane (2) (2-5%); 1,4-butanediol (3) -> tetrahydrofuran (4) (85%); 1,5-pentanediol (5) -> tetrahydropyran (6) (72%); 1,6-hexanediol (7) -> oxepane (8) (55-68%). Increased alkyl substitution at the carbinol carbon significantly diminishes the facility for cyclic ether formation. For example, a mixture of meso- and d,1-2,6-heptanediol gave only 6-10% of the cis- and trans-2,6-dimethyltetrahydropyrans when treated with DTPP. While diol 1 resists cyclodehydration with DTPP to oxetane, some 2,2-disubstituted 1,3-propanediols are readily converted to the appropriate oxetanes [e.g., 2-ethyl-2-phenyl-1,3-propanediol 3-ethyl3-phenyloxetane (78%)]. Treatment of diol 9 with DTPP gives starting material and ethyl ether 10 (32%) but no bicyclic oxetane. trans-2-Hydroxycyclohexyl 2-hydroxyethyl sulfide (11) reacts with DTPP affording 63% of trans-1,4-oxathiadecalin (12) and none of the corresponding cis isomer. These results indicate that the primary hydroxyl group undergoes preferential activation by DTPP and subsequent displacement as TPPO.

c X o » 9

a 10

>

c

11

0097-615 6/ 81 /0171-0165$05.00/ 0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

q 12

166

PHOSPHORUS CHEMISTRY

We have a l s o determined that the r e a c t i o n o f (Z)-2-bute.ne-l, 4 - d i o l with DTPP i n r e f l u x i n g dichloromethane (CH C1 ) a f f o r d s 2,5-dihydrofuran (85-87% GLC and 60% i s o l a t e d y i e l d ) . On the other hand, treatment of (E)-2-butene-l,4-diol with DTPP i n chloro form ( 6 1 ° , 18 h) gave a d i s t i l l e d m a t e r i a l (42%) whose E NMR spectrum was completely superimposable on an authentic sample of 3,4-epoxy-l-butene (13). This r e s u l t i s i n agreement with the r i n g closure p r e d i c t i o n s o f Baldwin where the 3 - e x o - t r i g cy c l i z a t i o n i s p r e d i c t e d t o be favored (2). 2

2

l


ff

,f

DTPP h

42%

Stereochemical information on the mode o f cyclodehydration o f unsymmetrical d i o l s t o c y c l i c ethers could o b v i o u s l y have import ant consequences regarding u s e f u l , p r e p a r a t i v e routes t o c h i r a l c y c l i c ethers o f high enantiomeric p u r i t y . For example, dioxyphosphorane promoted cyclodehydration o f a c h i r a l d i o l can, i n p r i n c i p l e , g i v e the enantiomeric ethers by e i t h e r of two stereochemic a l l y d i s t i n c t routes. Separate stepwise decomposition o f oxyphosphonium b e t a i n e s , A and B, although proceeded by a number o f e q u i l i b r i a could u l t i m a t e l y a f f o r d a nonracemic mixture of c y c l i c ethers. Ph P(OEt) + H0(CH ) CH(0H)R Λ

3

+ Ph

P

Λ

CŒ ) 2

2

n

2 EtOH

+ J*

n

1

^u\/ \ *CH

2

\

^

Ph

*CHR

X\

3PS\

(n-1-3; R=Me,Ph)

(CH ) 2

n

. 0

Β

A

•

/A \ • (CH )—CHR

Pn P0 3

^

2

* The r e s u l t s (Table I) i n d i c a t e that the c o l l a p s e o f betaine Β a f f o r d i n g l a r g e l y r e t e n t i o n of stereochemistry at the c a r b i n o l car bon (91.8-96.4%) i s h i g h l y favored. While the length o f the hydro carbon chain does not appear to i n f l u e n c e the stereochemical course o f the c y c l o d e h y d r a t i o n , the % r e t e n t i o n a t the c h i r a l c a r bon i s diminished s l i g h t l y when a phenyl group replaces a methyl group (Entry 1 and 4 ) . This may imply formation o f a b e n z y l i c carbocation with the expected l o s s o f stereochemical i n t e g r i t y . We have excluded pathways which might i n v o l v e concerted decom p o s i t i o n of dioxyphosphoranes to c y c l i c ethers with r e t e n t i o n o f stereochemistry at l e a s t f o r symmetrical 1,2-diols by examining the r e a c t i o n o f jd,l-2,3-butanediol with DTPP. The C NMR spectrum of the r e a c t i o n mixture i s c o n s i s t e n t only with the c i s epoxide e x h i b i t i n g resonances at δ 12.9 and 52.4 ppm. l â

In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

33.

BASS ET A L .

Table I . Entry 1 2


3 4

Cyclodehydration

and Chlorination

of

167

Diols

Stereochemistry o f Cyclodehydration o f D i o l s w i t h DTPP %Optical Diol Purity C y c l i c Ether % Ret

(S)- (+)-l,2-Propanediol 00- (-)-l,3-Butanediol 00- (-)-l,4-Pentanediol (S)- ( + ) - l - P h e n y l - l , 2 ethanediol

2-Methyloxirane

96.4

100

2-Methyloxetane

95.6

100

2-Methyloxolane

93.8

1-Phenyloxirane

91.8

71.4

97.5

During the course o f our work with DTPP, we became i n t e r e s t e d i n developing other u s e f u l and e f f e c t i v e c y c l o d e h y d r a t i n g "media" f o r d i o l s and t r i o l s , w i t h p a r t i c u l a r emphasis on TPP and t e t r a chloromethane ( C C l ^ ) . When trans-1,2-cyclohexanediol i s t r e a t e d with equimolar TPP i n excess C C l ^ , a 88% y i e l d of t r a n s - 2 - c h l o r o c y c l o h e x a n o l can be r e a l i z e d w i t h no evidence ( H, C NMR, GLC) f o r t r a n s - 1 , 2 - d i chlorocyclohexane or c i s - 2 - c h l o r o c y c l o h e x a n o l . Since the trans c h l o r o h y d r i n c o u l d not a r i s e from simple displacement o f TPPO by c h l o r i d e i o n w i t h r e t e n t i o n o f stereochemistry ( 3 ) , we suspected the intermediacy o f cyclohexene oxide which could subsequently undergo r i n g opening by the h y d r o c h l o r i c a c i d (HC1) generated i n solution. T h i s was e a s i l y proven by r e p e a t i n g the r e a c t i o n i n the presence of s o l i d potassium carbonate and r e a l i z i n g a 86% y i e l d of cyclohexene oxide and no c i s o r t r a n s c h l o r o h y d r i n s . Treatment o f d i o l 1 w i t h TPP-CCl^ i n CH CN s o l v e n t g i v e s predominantly 3-chloropropanol (75%) and 1,3-dichloropropane (16%) but no oxetane. I t i s u n l i k e l y that some 3-chloropropanol i s a consequence o f r i n g opening of 2 with HCI s i n c e r e p e a t i n g the r e a c t i o n i n the presence o f K 2 C O 3 7 an BC1 scavenger, gave i d e n t i c a l results. We have observed that d i o l 3, c i s - 2 - b u t e n e - l , 4 - d i o l , and c i s i,2-bis(hydroxymethyl)cyclohexane r e a c t smoothly with TPP-CCli to a f f o r d 4 (78%), 2,5-dihydrofuran (65%), and c i s - 8 - o x a b i c y c l o [ 4 . 3 . 0 ] nonane ^84%). Reaction o f d i o l 5 with TPP-CCl^ i n CH3CN g i v e s 52% of 5-chloropentanol, 6 (11%), and 1,5-dichloropentane (25%) while d i o l 7 a f f o r d s 6-chlorohexanol (48%) and 1,6-dichlorohexane (39%). Comparisons of the ether : c h l o r o h y d r i n : d i c h l o r i d e product d i s t r i butions a r i s i n g from these simple d i o l s r e v e a l a trend f o r e f f i c i ency of chain c l o s u r e to 3 7 membered r i n g s where the formation of c y c l i c ethers appear to decrease i n order of the f o l l o w i n g r i n g size: 3 ~ 5 > 6 > 4 ~ 7 . In an attempt to prepare b i c y c l i c ether 12 by c y c l o d e h y d r a t i n g d i o l 11 with one equiv of TPP i n CCli+, we d i s c o v e r e d a r e g i o s p e c i f i c c h l o r i n a t i o n of the primary hydroxyl group a f f o r d i n g X

15

3

f


168

PHOSPHORUS CHEMISTRY


trans-2-hydroxycyclohexyl 2 - c h l o r o e t h y l s u l f i d e (14) i n 70% y i e l d . Formation o f 14 may r e s u l t from c h l o r i d e displacement of TPPO o r c h l o r i d e capture of a t h i i r a n i u m i o n formed by neighboring s u l f e n y l s u l f u r displacement o f TPPO. The r e l a t i v e l y s m a l l amount of 12 (6%) formed i n t h i s r e a c t i o n may r e s u l t from (a) i n t r a m o l e c u l a r c y c l i z a t i o n of 14, capture of a t h i i r a n i u m i o n by the hydroxyl group, or (c) betaine (e.g., B) c o l l a p s e to ether 12 and TPPO.

ci+

d(V âfpC!v (Xv 11

14 1 eq TPP 2 eq TPP

i+

co

15

70% 39%

12

0% 48%

6% 13%

When d i o l 11 i s allowed t o r e a c t with 2 equiv of TPP-CCl^, c h l o r o h y d r i n 14 and 12 are formed as w e l l as t r a n s - 2 - c h l o r o c y c l o h e x y l 2c h l o r o e t n y l s u l f i d e (15) i n 48%. The evidence seems firm that f o r mation o f 15 must a r i s e from the intermediacy o f a t h i i r a n i u m i o n which allows f o r r e t e n t i o n of c o n f i g u r a t i o n during the HO -* CI conversion at Οχ. T h i s i s f u r t h e r supported by the f a c t that trans-2-thiomethyl cyclohexanol under s i m i l a r r e a c t i o n c o n d i t i o n s (1 eq TPP i n CCl^) gives o n l y trans-2-thiomethylcyclohexyl c h l o r i d e (62% by C NMR). By c o n t r a s t , the r e a c t i o n of trans-2methoxycyclohexanol with TPP-CCl^ gives e x c l u s i v e l y cis-2-methoxyc y c l o h e x y l c h l o r i d e a r i s i n g from c h l o r i d e displacement of TPPO with complete i n v e r s i o n o f stereochemistry at . Our present f i n d i n g s corroborate the r e s u l t s o f B i l l i n g t o n and Golding where i t was de termined that the r e a c t i o n between CH SCH *CH 0H and TPP-CCl^ gave a mixture (1:1) o f CH S*CH CH C1 and CH SCH *CH CI (*CH = C en r i c h e d methylene carbon)(4). TPP=triphenylphosphine; DTPP=diethoxytriphenylphosphorane; TPP0= triphenylphosphine oxide ; GLC= g a s - l i q u i d chromatography. 1 3

3

2

2

1 3

3

2

2

3

2

2

2

Acknowledgement i s made to the N a t i o n a l Science Foundation (CHE 78-05921) and Research Corporation f o r support o f t h i s research. Literature Cited

1. 2. 3. 4.

Chang, B. C.; Conrad, W.; Denney, D. B.; Denney, D. Z.; Edelman, R.; Powell, R. L.;White, D. W. J. Am. Chem. Soc. 1971, 93, 4004. Baldwin, J. E. J. C. S. Chem. Commun.1976, 734. Jones, L. A.; Sumner, C. E.; Franzus, B.; Haung, T. T.-S.; Snyder, Ε. I. J. Org. Chem. 1978, 43, 2821. Billington, D. C.; Golding, B. T. J. C. S. Chem. Commun. 1978, 208.

RECEIVED

June 30, 1981.


"Activated" Phosphoranes for the Cyclodehydration and Chlorination

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