Triphenylphosphane-diethylazodicarboxylate: A Useful System for

Nov 11, 1981 - Nucleophilic substitution reactions at alcoholic substrates with HX initiated by activation of the hydroxy-group by means of TP?/DEAD f...
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Downloaded by QUEENSLAND UNIV OF TECHNOLOGY on October 14, 2014 | http://pubs.acs.org Publication Date: November 11, 1981 | doi: 10.1021/bk-1981-0171.ch004

Triphenylphosphane-diethylazodicarboxylate: A Useful System for Directed Structural Variation of Carbohydrates E. ZBIRAL, H. H. BRANDSTETTER, and E. MARK Institute for Organic Chemistry, University of Vienna, A-1090 Vienna, Austria

Nucleophilic s u b s t i t u t i o n reactions at a l c o h o l i c sub­ strates with HX initiated by a c t i v a t i o n of the hydroxy­ -group by means of TPΡ/DEAD first developed by Hitsunobu (1) are being increasingly utilized (1,2). This p r i n ­ c i p l e has been seldom applied until now in the field of carbohydrates. In order to diminish h y d r o p h i l i c i t y , the mono- and b i s - t - b u t y l d i m e t h y l s i l y l e t h e r derivatives of a series of carbohydrates were prepared, which repre­ sent very useful substrates with two or even three free OH groups f o r r e a l i z i n g a series of i n t e r e s t i n g transformations by means of TPP/DEAD or TPP/DEAD/HX. The methyl-β-glucopyranoside 1a can be transformed in t h i s way e x c l u s i v e l y to the 3-desoxy-3-X-allose derivatives 2a-2d (X = N , Br, J, p-NO -C H COO) (figure 1), whereas the corresponding methyl- -D­ -glucopyranoside 1b gives e x c l u s i v e l y the analogous 4-desoxy-4-X-galactose derivatives 3a-3d. This useful s u b s t i t u t i o n reaction e s p e c i a l l y by means of TPP/DEAD/ can be applied also to the methyl-2-acetamido-63

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Figure 1. ( t - b u t y l d i m e t h y l s i l y l ) - 2 - d e s o x y - -D-glucopyranoside 4 and methyl-2-acetamido-3,6-bis-O-(t-butyldimethyls i l y l ) - 2 - d e s o x y - -D-glucopyranoside 5. The former i s 0097-6156/81/0171-0021$05.00/ 0 © 1981 American Chemical Society In Phosphorus Chemistry; Quin, L., et al.; ACS Symposium Series; American Chemical Society: Washington, DC, 1981.

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transformed to the methyl-2-acetamido-3-azido-6-O(t-butyldimethylsilyl)-2,3-didesoxy-oc-D-allopyranoside 6.whereas the l a t t e r goes over to the corresponding galactose derivative J . When la., Vb and 4 are treated with TPP/D~:AD alone the preparatively useful 3,4-anhydro-galactose derivatives 8 (methyl~3,4-anhydro2,6-bis-C-(t-butyldimethylsilyl)-B-D-galactopyranosid), 9 (methyl-3,4-anhydro-2,6-bis-C-(t-butyldimethylsilyl)-D-galactopyranosid) and K) (methyl-acetamido-3# 4anhydro-6-0-(t-butyldimethylsilyl)-?-desoxy- oL -Dgalactopyranoside) a r i s e . Under s i m i l a r conditions m e t h y l - 6 - C - ( t - b u t y l d i m e t h y l s i l y l ) - oC-D-glucopyranoside 11 y i e l d s the methyl-2,3-anhydro-6-0-(t-butyldi­ me t h y l s i l y l ) - o c - a l l o p y r a n o s i d 12. which can be sub­ jected a d d i t i o n a l l y an s u b s t i t u t i o n process at 04 by means of TPF/Dl'AD/HJNj resp. p-i^-CôZl^CQOH without any opening of the oxirane function by i l l . Kethy1-2,3-anhydro-4-azido-6-0-(t-butyldimethylsilyl)-4-desoxyot D-gulopyranoside 13a and methyl-2,3-anhydro-6-0-(tbutyldimethylsilyl)-4-0-(p-nitrobenzoyl)- ot -D-gulo­ pyranoside 13b are formed. The transformations of 2,6-0-bissilyl-methyl-oCD-mannopyranoside are represented i n figure 2. The predominating product i s the methyl-3,4-anhydro-talopyranoside 1j| even when TPP/DEAD/HII3 i s used. Obviously the s u b s t i t u t i o n process leading to the altro-sugar 16 i s greatly hindered by the w e l l known 1,3-diaxial i n t e r a c t i o n . A l l the epoxy sugars 8, J_C and 1£ serve as very useful s t a r t i n g points for further i n t e r e s t i n g s t r u c t u r a l modifications by opening the epoxide r i n g with EX (£, J5).

Figure 2. The behaviour of the :;-1,4-gluconolactone d e r i v a ­ t i v e JJ7 towards TrP/DIAD/ILX i s summarized i n figure 3· The exclusive a c t i v a t i o n of the Oil group at C5 using one equivalent ΤΡΓ/DF.AD followed by a s u b s t i t u t i o n by :,X opens an i n t e r e s t i n g approach to the L-1,4-idonolactone derivative 1_8 whereas the a c t i v a t i o n of the second Oil group at C3 y i e l d s by an e l i m i n a t i o n process

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

4.

ZBIRAL E T A L .

Structural

Variation

of

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the u n s a t u r a t e d s u g a r l a c t o n e 1 2 · By a p p l y i n g s u c h procedures to the analogous ? "5-bis-0-(t-butyldimethyls i l y l ) - e t h e r d e r i v a t i v e o f D - 1 , A - g a l a c t o n o l a c t o n e 20 the c o r r e s p o n d i n g L - a l t r o n o l a c t o n e d e r i v a t i v e s 21a (X = h j ) and 21b (X = p - ï ^ - C g l i / C C O ) o n t h e one a n d 2,6-bis-0-(t-butyldimethylsilylT-5-C-p-nitrobenzoyl-Lerythro-hex-2-en-1,4-lactone 22_ o n t h e o t h e r h a n d a r e r e s u l t i n g , A s i m i l a r p a t t e r n c a n be o b s e r v e d i n the case o f the 2 , 6 - b i s - 0 - ( t - b u t y l d i m e t h y l s i l y l ) - e t h e r

Downloaded by QUEENSLAND UNIV OF TECHNOLOGY on October 14, 2014 | http://pubs.acs.org Publication Date: November 11, 1981 | doi: 10.1021/bk-1981-0171.ch004

f

>SiO-i HO-f

=

*

S

TPP/PEAD

TPP/DEAD

i

°lx

T

ÎHX)

HX

19

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S

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-

Figure 3.

d e r i v a t i v e o f L - m a n n o n o l a c t o n e 2£. By o m i s s i o n o f HX t h e o l e f i n s u g a r l a c t o n 2J- ( 2 , 6 - b i s - G - ( t - b u t y l d i ­ methylsilyl )-3-desoxy-L-erythro-hex-2-en-1,4-la.ctone) i s formed w i t h o u t any involvement o f the C5-0H. I n c o n t r a s t the D-1,4-gulonolactone d e r i v a t i v e 2j? i s t r a n s f o r m e d i n t o t h e 3 , 6 - a n h y d r o - D - g u l o n o l a c t o n e 26 (figure 4)·

Figure 4.

The 4 , 9 - b i s - O - a n d 4,8,9-tris-O-t-butyldimethyls i l y l e t h e r d e r i v a t i v e s 2J_ a n d 2 8 o f t h e b i o l o g i c a l l y important neuraminic acid represent useful starting p o i n t s f o r t h e s y n t h e s i s o f t h e new s t r u c t u r a l l y v a r i e d n o n u l o s o n i c a c i d d e r i v a t i v e s 29 ( f i g u r e 5 ) 30 a n d 2l ( f i g u r e 6 ) . O p e n i n g o f t h e o x i r s n e r i n g o f 29 w i t h HI.jleads to the 8-desoxy-8-azido-neuraminic p c i d d e r i v a t i v e 30 w h i c h c o r r e s p o n d s completely 28. B y t h e r e a c t i o n o f t h e t r i s - s i l y l e t h e r d e r i v a t i v e 28 w i t h TPP/DEAD/MW5 a n i n t e r e s t i n g r e s u l t w a s o b s e r v e d

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

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( f i g u r e 6). The p r i m a r y a c t i v a t e d OH group o f 07 i s a t t a c k e d o b v i o u s l y as a r e s u l t o f i d e a l s t e r e o e l e c t r o n i c c o n d i t i o n s by t h e acetamido group o f 05· As a consequence o f t h i s n e i g h b o u r i n g group p a r t i c i p a t i o n an i n v e r s i o n o f t h e c o n f i g u r a t i o n o f 07 l e a d i n g t o t h e D-glycero-L-altro-5-(5 -methy1-1-N-tetr? zolo)-nonulos o n i c a c i d d e r i v a t i v e J5J_ o c c u r e d . Downloaded by QUEENSLAND UNIV OF TECHNOLOGY on October 14, 2014 | http://pubs.acs.org Publication Date: November 11, 1981 | doi: 10.1021/bk-1981-0171.ch004

1

Figure

6.

Literature cited 1. O. Mitsunobu, Synthesis 1981, 1-28 2. Η.Η. Brandstetter, E. Z b i r a l , Helv.Chim.Acta 1978, 61, 1832, 1980, 63, 327 3. Ε. Mark, Ε. Z b i r a l , Η.Η. Brandstetter, Mh.Chem. 1980, 111, 289. RECEIVED June 30, 1981.

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