COMMUNICATIONS Keywords: glycosylations . N M R spectroscopy * oligosaccharides . solid-phase synthesis . synthetic methods I 95 ~ 2) 1001 C'3 x i 3 5 1 50 49 48 47 4 6 4 5 4 4 4 3 42 41 4 0 3 9 38 37 /I - -6 Figure 2. I h g n o s t i c region of the 'H-'.'C H M Q C N M R spectrum o f 3 Thc spectra show that HR-MAS can bc used for monitoring the solid-phase synthesis of oligosaccharidcs in a very sensitive fashion. Parenthctically, the measurements tend to confirm our earlier claim that solid-support coupling rcactions -using properly protected 1,2-anhydro sugars (at least in this series)- are highly stereoselective. even morc so than the solution-based couplings." 'I The original claim was based on thc finding that no a-linkcd products could be found upon cleavage from the polymer and subsequent purification. Of course, arguments of this sort arc subject to uncertainties as to whethcr other stereoisomers might have been inadvertently overlooked during the removal and purification sequcnce. The argument becomes more persuasive as one cxamines thc "crude reaction mixture" bound to the solid phasc. While the data we obtaincd cannot exclude adventitious overlapping of signals from small amounts of isomcric %-products, it certainly indicates a high degree of control of each coupling event conducted on the solid phase. We attribute this exccllent B-stereoselectivity in this and related solid-state experiments19, l o ] to the relative diminution of cffective solvation upon complexation of thc oxirane by the zinc chloridc promoter. Solvation forces can lend the anomeric oxiranyl donor oxonium-like qualities. A donor spccies, which is far advanced in the direction of a free oxonium ion, is likely to be responsible for the formation of small but significant amounts of a-glycosides from the solution-based a-epoxide donor. In summary, the development of novel methodologies for thc assembly of oligosaccharides on the solid support will undoubtedly benefit from this disccrning "on-resin" analytical method. Chemists will be able to determine whether coupling has occurred and quickly estimate the specificity of the coupling step. Complete assignments can be madc aftcr the product is cleaved from the solid support and deprotected. E,qwitnenfal Section All specti-a were obtained on a Bruker DKX500 spectrometer. operating a t 500.13 M H r ( ' H ) and 125.76 MHz ("C). equipped with a 4 m m Bruker CCA HR-MAS probc. Trisaccharide 3 (20 mg at 0.54 nimo1g-l loading, 10.8 pmol) was loaded into a ceramic rotor. suspended in 30 p L CDCI,, and spun at the magic angle at 3.5 K H r ' H N M R spectra were obtained with a Carr-Purcell~Meihoom-(iill pulse sequence . 128 transients (1.64 s acquisition time. 0.5 s relaxation delay) were accumulated. The 13C['H: spectrum was obtained in 2 h 10 i n i n (3000 transients. 0 6 s acquisition time. 2 s relaxation delay). The phase-sensitive (TPPI) ' H - "C H M Q C spectrum was obtained i n 2 h (16 scans per 256 increments. 0.17 s acquisition time, 1.3 s relaxation delay) with a BIRD sequence to minimi7e resin sigiials "41. Total time for ' H , "C. and H M Q C N M R experiments was 4 h 15 inin. Received. July 3, 1996 Revised vcrsion' October 7. 1996 [Z9291 IE] German version: A n p i i ' . C k m . 1997. I O Y , 507 510 A. Giannic. Afigeii. U i e i i 7 1994. 106. 188: Aii,cyir. Ciiriii. / f i r Ed. h g l . 1994. 33. 178: C.-T. Yuen. Bezouska. J. O'Brien. M Stoll. R. Lcmoine. A. Lubineau. M. Kiso. A. Hasegawa. N.J. Bockovich. K . C. Nicolaou, T Feizi, .I Biol Chcv??.1994, 269, 1595; A. Vxki, P m . Nritl. A r i d Sri USA 1994. 91, 7390. M 1. Phillips. t. Nudelrnan. E C. A. Gaeta. M. Perm. A. K. Singhal, S Hakamori. J. C. Paulson, S<I(WP1990. 250. 1130. L.M Stoolman. Ceii 1989, 56, 907; L A Lasky, ihiri 1992. 258. 964 K. 0 . Lloyd, Ani .I Chi Prithoi. 1987. 87, 129, C. A. Ryan. P i o r ' iV(/r/. Amid Sci. USA 1994, Y l , I ; M. Meldal. S. Mouritsen. K Bock i n C(/i-h(~/i~,r/i.~iti, Antigms (Eds: P J. Garcgg, A. A. Lindberg). American Chemical Society. Washington DC. 1993. p 19 (ACS Simp Sw. 519). T Feizi, C i m . Opii7. S / r . u ~ tBioi. . 1993. 3, 701 K. 0. Lloyd. Crinccr. B i d 1991. 2. 421: K.0 Lloyd. L J Old. C ' I I N ~ C Re,\. ~. 1989. 4Y. 3445; K Ftikushiina. M Hiroto. P I Terasaki, A Wakisnki, H. Togashi, D Chia. N. Suyama, Y. Fukushi. E. Nudelman, S Hakamori. i h d 1984. 44. 5279; S Hakamori, ihid 1985, 45.2405; M. P. Bevilaqua. R. M Nelson, .I C h . I i i w s t . 1993. Y I , 379. R. B. Merrifield. I . Singer. B Chait. A n d Bio</ioii. 1988. 174. 199. M H. Caruthers. Sriefiw 1985. 2311, 281 J. M. J t.rechet in Poli.iiio--Siip/)ortrrl Rrwrionr iii Or,q(/riir j'< i i r h r x s (Eds : P. Hodge. D C. Sherrington). Wiley. Chichester, 1980. p. 1. Reviews G.-J Boons. Rwcihcdrori 1996, 52, 1095: G . H. Veencman. S. Notcrmans, R M. 1. Liskamp. G A. van der Marel, J. H. van Boom, 7Ltrrr/ie(Jron Lett. 1987, 28. 6695; L Y m . C. M. Taylor. R Goodnow, D . Kahne. J. An7. C1'1rn7.So<. 1994. 116, 6953; S. 1'. Douglas, D. M. Whitfield. J. .I. Krepinsky, ihid 1991, 113, 5095. S. J. Danishefsky. M T. Bilodenu. Afigmr Ci'wii. 1996, 108, 1482; Aiigcw C h i . hi/. Ed Efig/. 1996, 35, 1380. S. J Danishefsky. K. t McCIure, J. T. Randolph, R. B. Ruggei-i. Sci~.,mw1993. 260, 1307; J Y. Roberge. X Beehe, S. J. Danishefsky. i h d 1995, 26Y. 202. G . C Look, C. P. Holmes, J. P. Chinn. M A Gallop. .I 0r.g C%iw.1994. 59. 7588: k.. Albericio. M Pons. E. Pedroso. E Giralt. ibrd 1989. 54, 360; M Mazure, B Calas. A. Cave. J. Parello. C. R A u i d S(i. Scr. 2 1986. 303, 553; A. G. Ludwick. 1.W. Jelinski. D. Live. A. Kintanai-.J. J Dumais. J An?. C / i ~ i i ~ . So(..1986, /OK. 6493, F Bardella. R Eritja. E. Pcdroso. E. Gii-alt. Bioorg. Med. Ciioi?. Lei! 1993, 3. 2793; H . M. Eggenweiler. E Baycr. presented iit the Fourth lntri-national Symposiuin on Solid-phase Synthesis, Edinburgh. 1995. P. A Keifer. 1.Baltusis. I> M. Rice. A . A . Tymiac. 1 N . Shoolery. .I M ~ g n Rm. A 1996. 119. 65: S S. Sarkar, R S Gargipati. 1. L Adams. P. A Keii'er, I Am Cheix. S i x 1996, 118. 2305, W. 1.Pitch. G. Detre, C. P Holines, J. N. Shoolery. P. A. Keifer, J Oig. Ciitw. 1994. 59. 7955; R. C. Anderson, M. A. Jarema, M. J. Shapiro, J. P. Stokes. M. Ziliox. ihirl. 1995, 60, 2650. H. Y Carr, E. M Parcell. PhJs. Kci,. 1954. Y4. 630; S. Meihoom, D. Gill, Rev. Sci fnsri- 1958. 29, 6% A Bax. S. Subrumanian, J Mugn. Rcson. 1986, 67, 565. S. J. Danishefsky, R. L. Halcoinb, J Aiii. C ~ E I Soc. I I 1989. 111. 6661 Novel Carbocyclic Ring Closure of Hex-5-enop yr anosides Sanjoy Kumar D a s , Jean-Maurice Mallet, and Pierre S h y * Carbohydrates have been used as starting inaterials for thc synthesis of an extcnsive rangc of cnantiomerically pure noncarbohydrate natural products and relatcd substances.' The intramolecular ring closurc of carbohydrates to form carbocyclic compounds is an attractive transformation. which offers direct access to highly runctionalized cyclohexane derivatives. In this [*] Prof P Sinay. Dr. S K. Das. Dr L M . Mallet Departement de Chirnie. URA 1686 Ecole Norrnale Suptrieure 24 rue Lhomond F-75231 Paris Cedex 05 (France) Fax: Int. codc +(1) 44-32-3397 e-mail . sinay:u chimenc.ens.fr COMMUNICATIONS ring-closure reaction a carbanionic center (C6) usually attacks the electrophilic carbonyl center (CI). An early example is the Grosheintz- Fischcr synthesisr2]of deoxy nitroinositols fi-om 6-deox y-6-nitrohexoscs. As predicted, the reaction of the known carbohydrate vinyl acetal lr141 with four equivalents of triisobutylaluminum (TIBAI) at 40 C resulted in the transposition of an oxygen atom on thc ring with the exocyclic carbon atom (Scheme 4). In 1979 Fcrrier reported the convenient conversion of an easily available hex-5-enopyranoside into a highly functionalized cyclohexane derivative in the presence of mercury(l1) ~ h l o r i d c . ' ~ ~ Hydroxymercuration of the vinyl ether moicty of a hex-5enopyranosidc gives an unstable hemiacetal, which loses 1 2,79% methanol to gcneratc a critical dicarbonyl interrnediatc Scheme 4. Typical example of the novel carbohydrate transposition. (Schcme 1 ) . This species then undergoes an aldol-like intraniolecular cyclization to form a substituted cyclohcxane. Mechanistic and stereochemical ~ t u d i e s [as ~ 1well as modified reaction The only isolatcd product of the reaction (79O/0) was the secconditions"] have been published. Highly functionalized cycloondary alcohol 2, which was formed by the subsequent stereohexanc derivativcs are of major significance for several groups selective reduction of the carbonyl group by TIBAl. Starting of natural products. This remarkable rearrangement--the Fermaterial (20%) was also rccovcred. ricr-I1 reaction[61---has provided a practical route to a large Although a detailed mechanism for the formation of 2 is still wriety of bioactive substanccs such as aminocyclitols, pseudoa matter of speculation (Scheme 5), the reaction is presumably sugars, and inositols.['] A basic feature of the Ferrier-I1 reaction is the loss of alcohol, for example methanol (Scheme I ) , and gcncration of an electrophilic aldehyde, which is necessary for the aldol reaction. L - Rs%LoH Schcmc 5. Probable incclianisin of the transposition Bn = b c n ~ y l OR Scheme I initiated[l3] by the coordination of the aluminum atom of TIBAl with the endocyclic enolic oxygen atom. This endo activation is followed by a ring opening step with the generation of the zwitterionic aluminum enolate intermediate A. Assuming that A retains its geometry on the time scale of the reaction, it may thcn undergo direct cyclization through a twist form," 51 thus keeping the anomeric stereochemical "memory". Alternatively, a rotation would give the intermediate B, which could then undergo cyclization through a chair-like six-membered ring. In this case, the electrostatic attraction bctwecn the positively charged oxygen and the negatively charged aluminum unit would hold the enolate in proximity to the C - 0 TC bond (tight ion pair), which nicely explains the obscrved stereochemical outcome. In both cases the intramolecular aldol condensation ~ O C Sthrough the favored['61 6-exo-trig process. The final reduction of the keto group with TIBAl leads exclusively to the alcohol 2 by intramolecular hydrogen delivery from the less hindcrcd side. Reaction of the vinyl acetal3 under the same reaction conditions provided the three secondary alcohols 4 in 70 %, 5 in 10 YO, and 2 in 6 % yield (Scheme 6, physical and spectroscopic data I'roposed mechanism for the Fcrricr-ll reaction . We now rcport an alternative, direct conversion of hex-5cnopyranosides into highly functionalized cyclohexane derivatives without cleavage of the glycosidic bond. Thc discovery of this novcl carbohydrate rearrangement is a result of a logical cieduclion from two indcpendcnt facts: 1 ) Acyclic products of thc selcctivc cleavage o f the ring carbon-oxygen bond of glycopyranosides have occasionally been observed upon treatment uith suitablc elcctrophilic species (Scheme 2). 2) Hex-5-eno- Sclienie 2. /Xi,activation iii glycosidc clcavagc pyranosides are vinyl acetals wilh a vinyl ether subunit as part o f an acctal moiety. Among the various reactions known (or vinyl a c e t a l ~ , ~ the ' ~ triisobutylaluminum-assistcd rcductive rearrangement provides an elegant cntry to substituted cyclobutancs,['"' cycloBnO pro pane^,^' 'I tctrahydrofurans,[' 21 and tetraBno%OCH3 hydropyransr'31(Scheme 3). jBU3A OBn PhMe,40°C BnO-oCH, B \ : m O C H 3 + OHOBn 4 (70%) 3 PhMe, -78°C FP S c l i m e 3 St~rcocoiiti-olledPetasis syiithevis  of suhstitut- ed t c1i-3h y d rep! r:i iis fl-oiii sii hst i t uted vinyl ‘ice t d l a A' Scheme 6. Application of the transposition to a 1-glucoside. 8' OBn 5 (10%) + 2(6yo) COMMUNICATIONS 'Table 1 Physical and spectroscopic data for 2, 4. 5. 7-9. 11. 12. and 14 [a]. + 2 : [r];' = - 9 (< = O.X in CHCI,): ' H NMR (250 MHL. CDCI,)- 6 = 7 3 - 7 1 (m. 15H. arom. H), 4.85 4.6 (in. 6H, 3 -CH,Ph). 4.09 (t. 1 H. ./(2,?) = 9 3. J(3.4) = 9 3 H7. H-3). 3.98 (dddd. I H. J(5,OH) = 9 5. .1(4,5) = 3.3, ./(5.6e) = 3 X. J(5.6a)=2.0Hz.H~5).36(ddd.1H,J(1.2)=2.9.J(l.ha)=2.0.J(l.6e)=3.8Hz. H-1),3.55(d, I H.OH).3.45(s. 3H,OMe),3.33(dd. 1 H. H-2).3.29(dd. 1 H. H-4). 2.2 ( d t . 1 H, J(6a.he) = 15.0 Hz, H-612). 1.25 (dt, 1 H.H-621) 9: Syrup. [r];" = 20 ( L = 0.9i n CHCI,). ' H NMR (250 MHL. CDCI,): 6 = 7 3 7.1 (20H. arom. H ) . 4.9-4.5 (m, 8H. 4 -CHiPh). 4 1 (1. 1 H. ./(2,3) = 9 2, ./(3.4) = 9.2 Hr. H-3). 4.0 (m.1 H. H-5). 3.9 (m.1 H, H-1). 3 7 (d. I H. ./(S.OH) = 9.4 Hz. OH). 3 32 (dd. 1 H. ./(1.2) = 2 8 Hz, H-2). 3.3 (dd. 1 H. J(4,5)= 3 . 4 H z . H - 4 ) . 2 . 2 ( d t . l H . J ( l . 6 e ) = 3.9.J(5,6e)=39,.1(6a.6e)=150H1', H-be). 1.3 (dt, I H. ,/(I.ha) = 2.0. .1(5.6a) = 2 0 H L . H-6a). [TI?! = + 8 ( ( , = I 7 in CHCI,); ' H N M R (250MHz. CDCI,): 0 = 7 3 (15H. arom. H). 4 X - 4.55 (m.6H. 3 -CH,Ph). 4.05 (dddd. 1 H. ./(4,5) = 3.1, J ( 5 , 6 a ) = 2.0, J ( 5 . 6 ~ = ) 4.4. J(5,OH) = 1.6 Hr. H-5). 3.73 ( t . 1 H. J(2.3) = 9.3, J(3.4) = 9 3 Hz. H-3), 3.60 (ddd, I H. 4 1 . 2 ) = 9.1, J(l.6a) = 12.0. J(1,he) = 2.28 ( d t , 4.4 HZ,H - l ) , 3.4 ( 5 . 3 H . OMc). 3.36(dd, 1 H, H-4), 3.30 (dd, 1 H.H-?), 1 H. J(6a.he) = 14.0 Hz. H-he), 1.2 (ddd, 1 H, H-ha). 5:Whitesolid.m.p. = 95 C , [ r ] i "= 3 5 ( r = 0.7inCHC13), 'HNMR(250MHz, CDCI,).6=7.3-7.15(s.15H.arom.H).5.0-4.6(m.6H,3-CH,Ph),35 3.l(m, 5 H , ring protons), 3.4 (s. 3H. OMe), 2.29 (dt, 1 H. J ( l , h e ) = 4 0 . .1(5,6e) = 4.0. J(6a,6e) = 12.0 Hz. H-he), 1.3 (ddd. 1 H,./(1,6a) = 12.0, J(5,6a) = 12.0 Hz. H-621). 7: White solid, m.p. =70 C; [z]iO= - 3 ( c = 0.95 in CHCI,); ' H NMR (250MHr. CDCI,): 6 =7 2 (m. 20H. arom. H). 4 9 - 4 5 (m, XH, 4 -CH,Ph), 4.01 (m, 1 H, H-5). 3.85 (ddd, 1 H. ./(l,2) = 9.4, J(1,ha) =11.3, J ( l . 6 ~ = ) 4.3 Hz. H-I), 3.75 (t, 1 H, ./(2,3) = 9.4. J(3.4) = 9 4 Hz. H-3), 3 4 (t, 1 H, H-2) 3.4 (dd. 1 H, H-4). 2.42 (bs, OH), 2.28 (dt. 1 H. .1(5.6e) = 4.3, J(6a.he) =13.7 Hz, H-6e). 1.30 (dd, I H, J(5.621) = 4.0 HL. H-68) 11:Whiresolid,m.p.=117'C.:," = + 3(( = l i n C H C I , ) : ' H N M R ( ~ ~ O M H L , C,D,,)-6=7.3-69(m.15H.arom H ) . 4 X 4.32(m.6H.3-CH,Pli).3.95(t.lH. 4: Syrup. .J(l,2) = 8.7. J(2.3) = X.7 Hz, H-2). 3 73 (dd. 1 H. H-3). 3.55 (in, 1 H, H-5). 3.48 (ddd, 1 H. J(1.6a) = 10.7. J ( 1 . 6 ~ = ) 4.0 H L . H - I ) , 3.42 (m. I H. H-4). 3.2 (s. 3H, OMeJ, 1.86 (ddd, I H. .1(5.6a) = 2 9 . .1(6a.6e) = l ? 5H7. H-6a), 1.72 (ddd, 1 H. J(5,6e) = 4.0 Hz, H-6e). + 12: White solid. m.p. = 97 C; [TI? = + 17 ( c = 0.8 in CHCI,): 'HNMK (250MHz. CDCI,): 6 = 7 . 3 (m.1SH. arom. H). 5.09. 4.55 (2d. 2H. . / = 1 2 5 H z . -CH,Ph).4.8(~,2H.-CH,Ph).4.70(ABq.2H.J=11.9 Hr:CHzPh).3.8S(dd. 1H. 43.4) = 2.4, J(4.5) = 1.5 Hz, H-4), 3.79 ( t . 1 H../(1,2) = 9.0..1(2.3) = 9.0 Hr. H-2). 3.47(ddd, 1H,.1(5.6a)=11.8../(5.6e)=5.0Hr,H-5),3.4(~.3H.OMe).3.32(dd. 1 H, H-3), 3.10 (ddd, I H . J(1.621) = 11.8. J ( 1 . 6 ~ )= 5.0 H/. H-I), 2.1 (s. 1 H, OH), 2.05 (ddd, J(6a,6e) = I 1 8 Hr. H-he). 1.67(ddd, 1 H. H-6a). 14: Syrup, [r]:,"= - 20 (c = 1.0 i n CHCI,), ' H N M R (250 MHL, CDCI,). 6 = 7 . 2 (in. I S H . arom. H). 4.7-4.4 (m. 6 H , 3 -CHzPli), 3.95 (dddd. I H . J(4.5) = 4.0. .1(5.6a) = 8.0. J(5.6e) = 4 0,./(S.OH) = 9.6Hr. H-5). 3.75 (dd. I H. J(2.3) = 6.0. J(3.4) = 2.7 Hz. H-3). 3.62 (dd. 1 H, J(1.2) =7.8 Hz. H-2). 3.62 (dd. 1 H. H-4). 3.50 (ddd. 1 H. , / ( 1 . 6 ~ = ) 8.0, ./(1,6;>) = 4.0 Hz, H-I). 3.32 ( s . 3H, OMe), 2.35 (d, 1 H.OH). 2.01 (dt. 1 H, J(6a.6e) = 13.0 Hr, H-6e). 1 65 (ddd. 1 H. H-6a). 8:Whitesolid.m.p. = I 2 1 C;[z]i"= + 2 5 ( ~ . = 0 . 9 5 i i i C H C I , J ; ' H N M R ( C D C I , . 250 MHr): 6 = 7 2 (m.ZOH, arom. H), 4.92-4.55 (m. XH,4 -CH,Ph). 3.55-3.34 (m.4H.ringprotons).3.23(t, IH..1=90Hz),2.2X(ddd, 1H, J = l l 5../=4.2. ./ = 4.2 Hz. H-6e). 1.37 (ddd, 1 H, ./(all) = 11.5 Hz, H-621). [a] All compounds gave correct elemental analyses. - B;;,ooBn are given in Table 1). Interestingly, 4 B~O=OBABU~A~ B n O D B n + -E + L : and 5 (that is, 80% of the products) reBnO BnO OBn PhMe, 40°C tain the stereochemical information of &OBn OBn OHoBnoBn the anomeric center. Again, this reac6 7 81 % 8 (5%) 9 9% tion may proceed through the ion pair Scheme 7. An expedient synthesis of an optically active protected monodeoxygenated derivative of n?j.o-inositol. A' o r the intermediate B'. Therefore, a distinctive feature of this entry to highly functionalized cyclohexanes is the retention of the anomeric stereochemical information in the starting glucoside. This is in sharp contrast to 80% BnO + " L O C H + BnO Bn&ocH the Ferrier-I1 reaction, where the reaction inherently BnO OBn OBn OBn requires an exo cleavage to eject the aglycon. hocH, , In the same manner, the benzyl glucoside 6 was 10 11 20% 12 60% converted into the alcohol 7 (83 %); isomers 8 (5%) and 9 (9%) were also isolated as minor products. Compound 7 has recently been prepared in racemic A H O F O OBn C H , 75% BnO form from qo-inositol (Scheme 7)." 'I + Finally, thc same conditions were applied to vinyl OCH OH OCH, OBn acetals 10 and 13 (Scheme8), which are derived 13 14 from methyl fi-D-galactopyranoside and methyl Z-DScheme 8. Application of the transposition to :I /~-galactomkand an r-mannoside mannopyranoside, respectively (Scheme 9). In the case of 10, the axially oriented benzyloxy group at C4 probably hinders reduction from the [j side; compound 12 is the major product (60 Y O ) . m T w R 1 % &: ;B B n O k R I 5 jR*: \B Ri BnO In conclusion, we have developed a R4 R2 R' novel, stereoselective access to substitutR' R' ed cyclohexane derivatives, starting 1 R'=MeO; Ri=R3=H; R4=OBn from hex-5-enopyranosides. A distinc3 R'=MeO; R2=R3=H; R4=OBn 6 R'=BnO; Rz==R3=H; R4=OBn tive feature of the reaction is the reten13 R'-MeO; Ri=R4=H; R3=OBn tion of the anomeric stereochemical information. An extension to disaccharides and ohgosaccharides is therefore OCH b BzO Bz& OCH3& c BzO B& OCH3 d BnO, e kOCH BZQ attractive. It would also provide an exOBz OBZ OBz OBn pedient and stereoselective entry to 10 pseudo disaccharides and oligosacchaScheme 9 Preparation ofthe hex~5~enopyranosides. a) LiAIH,. AICI,. CH,CI,. ether, 30 C (XO'X); b) 12, Ph,l'. rides,"81 which are Of Poimidazole. toluene. 7 0 ' C (XO"/;,);c) DBU. T H E reflux (75%); d ) MeONa. MeOH, RT, e) BnBr. NaH. DMF. tential biological interest." 91 RT (80%); Bz = benzoyl. DBU = 1,8-diarabicyclo[5 4 O]undec-7-ene Bn01 - , - - , COMMUNICATIONS E.\-pcrinwnuil Scclion A 1 M solution of ti-iisobutylaluminum in toluene ( I 8 inL. 1 8 mmol) was added to I (700 mg, 0.45 nimol) in freshly distilled. dry tolucne (15 ml) at 0 - C The reaction iiiixture w a r then stirred at 40 C for 6 h. After coinpletion of the reaction. exces? triisobutylnluininiim was quenched with ice-cold water The reaction mixture was filtered. and the organic phase separated. The water layer u'as extracted twice with ethyl acetate The combined organic fractions were dried (MgSO,) and concentrated. and the residue subjected to flash chromatography (eluent. cyclohexanr ethyl acetate 2,'l) to givc 2 as a syrup(158 mg. 79%) Received: Scptcinber 23 l W 6 [Z95851E] Ciei-man version A n p i i ' . ( ' h o i i . 1997. 109. 513- 516 Keywords: acetals * aluminum * carbohydrates . cyclohexane Transition Metal Germylene Complexes as Hydrogenation Catalysts: The Synthesis of a Rare Bis(amino)germane** Kyle E. Litz, J o h n E. Bender IV, Jeff W. Kampf, and Mark M. Banaszak Holl" Molecules in which germanium is bound to both hydrogen and nitrogen are surprisingly rare."' Of the known examples, namely, H,GeN, ,Iz1 H,GeNCS,r31H,GeNC0,[31(H,Gc),N,[~I F,CN=GeH2,Is1 H,GeN=C=NGeH,,[61 and Ph,(H)GeNR, ,[71 the first three complexes contain pscudohalogen ligands and thus resemble the well-established halogermancs. The fourth example, (H,Ge),N, is widely known to exhibit delocalized rc bonding and enhanced Ge-N bond strength, whereas Ph,(H)GeNR, is unstable and readily disproportionates to Ph2CcH, and Ph2Ge(NR,),. Other than (H,Ge),N, we are not aware of any aminogerniancs of stoichioinetry HGe(NR,), , H,Ge(NR,), , or H,GeNR, previously reported. In fact, amino groups are commonly employed as leaving groups when gerinancs arc formed by hydrogenation reactions, which makes the easily accessible complexcs of general stoichiometry CI,Ge(NR,),. unsuitable as precursors to aniinogermancs.[81 Standard approaches for making aminogerinanes, which iiivolve reagents such as LiAlH, and NaBH,, typically result in amine formation. Recently, we have synthesized H,Gc[N(SiMe,),], (1) and H,Ge[CH(SiMe,),], (2) by both stoichioinetric and catalytic routes using well-defined, threecoordinate, Group 10 metal germylene complexes of general stoichiometry [ (R,P),MGeR'J .[91 The thrcc-coordinate catalysts are similar to compounds previously reported by Lappert and co-workers.[lolIn addition, we have found that Nio complexes such as [Ni(cod),] (cod = 1,5-cyclooctadiene) can servc as catalyst precursors, even in the absencc of phosphane. The initially discovered routes to 1 and 2 made use of 3 and 4,as summarized in Scheme 1 : ' ' ' I Treatment of a benzene [I] S. Hancssian. Acc C/xwi. Re?. 1979. 12. 159. B. Fraser-Reid, C. Anderson, PIO~ c'/iN77. Orx. Nut. SVZ//I.M<,I/iod\ 1980, 39. 1 ; A. VtIsS~la.M d . S ~ ~ i t h . Mctiiodr 1980, 2. 173; S Hanessian. 7i>tril . ? w ~ r / i r . s i s of' Nrrfurtd P r u d i ~ t s ,The Chiroii Ap/)rouch. Peryamon. Oxford. 1983. 121 J. M Groshcintz, H. 0. L. Fischer, .I ,4171 (.hem S i x . 1948, 70, 1479; T. Iida. M. Funabashi, J Yoshimura, Bull. Clirni. So<. ./pn. 1973, 46, 3203; J. Kovac, H . H . Bacr, Cnrhohj-rlr Re.\. 1975. 45, 161. and references therein; review: H. H. Baer, Ads Curhohj.i/r. C / w n . Biodirw. 1969, 24, 67  K.J. Ferrier. .1. Chiwi. SOC.Perkrii Ti.ans 1 1979. 1455.  K.Yamanchi, T 'lei-achi, T. Eguchi, K. Kakinuina, Te/rrilie(/ron1994,50,4125; R . Blattncr. R. J Ferriei-. S. R Haincs, .I Chrni. Soc. I ' r v k i i i Ti.ans. 1 1985, 2413. A. S. Machado. D Dubi-euil. J Cleophax. S. D. Gcro, N. F.Thomas. (iirhohrdr. Rcs. 1992, 233. C S , P Laszlo. A. Dudon. J . Cui./w/rrdr. C/rm. 1992. / / . 587 [ 5 ] A. S . Miichado, A. Olesker, G. Lukacs, Curhohidi- Re< 1985, 13.5. 231; N. Cliida. M Ohtsuka. K Ogura, S. Ogawa. BE///. Chcni. Soc J p i 1991, 64. 21 18: S Adam, 7iJti-rrlicth-on Lett 1996. 37, 649  For a description of Fei-i-ier-lreaction5 see R. J. Fcrrier. A d v Ctri-holij d r C%em 1965. 20. 67.  Review' K J Ferricr, S. Middleton, Choii. Rcv. 1993. 93. 2779 [XI C. B. Post. M. Karplus. .I A m Choii. Soc 1986. /OK, 1317, Y Guindon, P. C. Anderson. 7i~friilictlroriLrtt. 1987, 28, 24x5; D. R McPhaiI. J. R. Lee, B. Fi-a\ri--Reid. .I. Aiw. Cliivn. So<.1992, 114. 1905  H. Frauenrath. Xmfhr.sir 1989, 721 [It)] K.Meiiicagli, C:. Malanga, L. Lardicci, .I Org. Chcrn. 1982, 47. 2288. [I I ] K Meniciigli. C. Malanga. M . Guidi. L. Lardicci. 7i,trohri/roii 1987. 43. 171. R. Municagli. C. Malangd. M. Dell'lnnocenti. L. Lardicci. J Org Cheii~1987, 52, 5700 1121 K.A. Petasis. S. 1' Lu. ./ Am. C/iom Snc 1995. 117. 6394. 1131 h.A. Petcisis. S P Lu. 7i~trir/1cr/ro11 Lrti 1996. -1'7. 141. excess PEt3 [I41 K. Sakairi. H Kuruhara, 7 ? / r i h r h i i L<,/t. 1982. 23. 5327. [IS1 T. Timori. H . Takahashi, S. Ikcgami, 7i~trrilictlroiiLei!. 1996. 37, 649, see ref'. Et3PI, HZ Et3P, ,H  of this cominunication. Pt --Ge[N(SiMe3)z]2 @ ,Ptbe:N(SlMe3h [I61 .I. E. Baldwin. M J Lush. 7i~rrahrdron Etp' -H2 Et3P 3 1982. 19.2939. N(SiMe,h [ 171 J. Yu. J. B. Spencer. .I Org Ckm7 1996. 61,3234 [ I X ] S Ogawa. S -1. Sasaki, H Tsunoda. Crrrhohi-h- Re\ 1995, 274. 183, and references therein. Et,Pi, H2Ge[N(SiMe31212 + 'Pt --Ge[CH(SiMe,t, [I91 J F..' Duiis. K. Bock. S Opiwa. Cbi-hii/i)ili R i d \ 1994. 252. 1. Et3P. T k l2 5 1 Scheme 1. Synthetic route to 1 [*I [**I Prof. M. M . Banaczdk Holl. K. k.Litr, Dr. J. W. Kampf Chemistry Department, University of Michigan Ann Arbor. MI 4x109-1055 [USA) Fax: Int. code +(313)763-2307 e-mail' mbaiia%i:ir umich.edu J. E. Bender 1V Chemistry Department. Bi-owii University Providence, R1 02912 (USA) 'Theauthors thank AIf;i-Aesai- for agenerous loan of KIIPtCl,] and the University of Michigan for financial support of this work. J. E. B. thanks the N S t for a graduate fcllowsliip.