3AA 氨基酸(ABNO介导哌啶类化合物的电化学氧化alpha-氰基化反应)

鏈枃鏉ヨ嚜寰俊鍏紬鍙凤細X-MOLNews鈥嶁€嶁€嶁€?/strong>

鍝屽暥鏄疐DA鎵瑰噯鐨勮嵂鐗╀腑甯歌鐨勬潅鐜粨鏋勶紝鍏锋湁鑹ソ鐨勮嵂鐗╁姩鍔涘鎬ц川锛堝浘1A锛夈€傜幆鑳轰腑N閭讳綅C-H閿殑瀹樿兘鍖栦竴鐩存槸浜轰滑鍏虫敞鐨勭劍鐐癸紝浠ュ線璁捐璇ョ被鍙嶅簲澶氭槸鍒╃敤N淇濇姢锛堝嵆N-閰板熀鎴?em>N-鑺冲熀/鐑峰熀锛夌殑涓夌骇鑳鸿鐢熺墿浣滀负搴曠墿杩涜锛岃繖浜涘寲鍚堢墿鍦ㄨ嵂鐗╁悎鎴愪腑鍙埄鐢ㄤ环鍊煎皬锛屾皑鍩轰繚鎶?鑴变繚鎶ょ箒鐞愮殑鎿嶄綔杩囩▼涔熼檺鍒朵簡浜轰滑瀵逛簩绾у搶鍟剁被鍖栧悎鐗╃殑鏈夋晥鍒╃敤銆傚洜姝わ紝寮€鍙戜簩绾у搶鍟剁被鍖栧悎鐗〤-H閿洿鎺ュ畼鑳藉寲鐨勬柟娉曢潪甯稿繀瑕併€?/p>

杩戞棩锛?strong>缇庡浗濞佹柉搴锋槦澶у楹﹁开閫婂垎鏍″寲瀛︾郴鐨?strong>Shannon S. Stahl鏁欐巿璇鹃缁勫湪J. Am. Chem. Soc. 涓婂彂琛ㄦ枃绔狅紝鎶ラ亾浜?strong>鐢靛寲瀛︽柟娉曞疄鐜颁簩绾у搶鍟剁被鍖栧悎鐗㎞閭讳綅C-H閿殑姘у寲姘板熀鍖?/strong>锛屽弽搴旀棤闇€瀵瑰搶鍟剁殑N-H閿繘琛屼繚鎶ゅ熀淇グ锛屽埄鐢?-姘潅鍙岀幆澹兎-N-姘у寲鐗╋紙ABNO锛変綔涓洪鍌寲鍓傦紝淇冭繘浜岀骇鍝屽暥鑴辨阿姘у寲褰㈡垚鐩稿簲鐨勭幆浜氳兒锛岃繘鑰屽彂鐢熸鞍鏍硅礋绂诲瓙鐨勫姞鎴愬緱鍒版渶缁堜骇鐗┿€傝鏂规硶闇€瑕佺殑鐢垫瀬鐢靛娍杈冧綆锛屼竴绯诲垪鏉傜幆缁撴瀯浠ュ強姘у寲鏁忔劅鐨勫熀鍥㈤兘鍙互寰堝ソ鍦板吋瀹广€?/p>

鍥?. 浜岀骇鍝屽暥绫诲寲鍚堢墿鐨勎?姘板熀鍖栥€傚浘鐗囨潵婧愶細J. Am. Chem. Soc.

姘板熀鍙互杞寲涓哄叾瀹冨绉嶅彇浠ｅ熀锛屽寘鎷晶閰搞€侀叞鑳恒€侀叜鍜岃兒绛夛紙鍥?B锛夈€傜洰鍓嶆姤閬撶殑宸ヤ綔浠呴檺浜庢椿鍖栧簳鐗╁鍥涙阿寮傚柟鍟夊拰涓夌骇鑳?閰拌兒琛嶇敓鐗╃殑姘板熀鍖栵紝灏氭棤鏅€傜殑鏂规硶鐢ㄤ簬浜岀骇鍝屽暥鐨勬鞍鍩哄寲锛屽弽搴旇繃绋嬩腑鐜簹鑳哄緢瀹规槗鍙戠敓鍒嗚В銆?/p>

浠ュ線鎶ラ亾鑳虹殑鐢靛寲瀛︽哀鍖栧弽搴旈€氬父鏄互涓夌骇鑳鸿鐢熺墿鍙戠敓鍗曠數瀛愯浆绉伙紙ET锛夊紩鍙戠殑锛岄殢鍚庡彂鐢熷揩閫熺殑璐ㄥ瓙鍜岀數瀛愯浆绉伙紙PT-ET锛夊舰鎴愮浉搴旂殑浜氶摰绂诲瓙銆備綔鑰呭湪杩戞湡鐨勭爺绌朵腑鍙戠幇锛屾爱姘у寲鐗╁弬涓庣殑鐢靛寲瀛︽哀鍖栧弽搴斿彲浠ヨ閬垮父瑙勭殑ET-PT-ET杩囩▼锛岄€氳繃鐢靛寲瀛︽哀鍖栦績杩涘簳鐗╃殑鐩存帴姘㈣浆绉汇€傛爱姘у寲鐗╁弬涓庣殑鍙嶅簲鑳藉湪杈冧綆鐨勭數鏋佺數鍔匡紙> 1 V锛変笅杩涜锛屼粠鑰屽ぇ澶ф墿灞曚簡瀹樿兘鍥㈢殑鍏煎鎬у拰搴曠墿閫傜敤鑼冨洿锛堝浘1C锛夈€?/p>

浣滆€呴鍏堥€氳繃寰幆浼忓畨娉曪紙CV锛夌爺绌舵湁鏃燗BNO鍙備笌鐨勬儏鍐典笅4-鑻熀鍝屽暥1a鐨勬哀鍖栬繕鍘熸儏鍐点€傚簳鐗?strong>1a鍦?39 mV澶勫憟鐜板嚭涓嶅彲閫嗙殑闃虫瀬CV鏇茬嚎锛堝浘2锛岀豢鑹茬嚎锛夛紝鑰屼綆鐢靛娍灏忎綅闃荤殑姘哀鍖栫墿ABNO琛ㄧ幇鍑篍_1/2= 195 mV鐨勫彲閫咰V锛堝浘2锛岀伆鑹茬嚎锛夈€傚惈鏈?strong>1a鍜孉BNO婧舵恫鐨凜V鍒嗘瀽琛ㄦ槑锛孉BNO姘у寲杩樺師鐢靛娍鐨勯槼鏋佺壒鎬ф樉钁楀鍔狅紝闃存瀬鐗规€х浉搴斿噺灏戯紙鍥?锛岀孩鑹茬嚎锛夈€侫BNO鍜?strong>1a鐨勯槼鏋佸嘲鍊肩數鍔匡紙螖E_p > 500 mV锛?缁胯壊涓庣孩鑹茬嚎锛変箣闂寸殑宸ㄥぇ宸紓琛ㄦ槑锛屽簳鐗╂哀鍖栨椂浜х敓鐨勭數鏋佺數鍔胯緝浣庢槸鐢盇BNO浠嬪鐨勬阿杞Щ寮曞彂锛岃€屼笉鏄數鏋佸紩鍙戠殑鐢靛瓙杞Щ瀵艰嚧鐨勩€?/p>

鍥?. 寰幆浼忓畨娉曠爺绌?strong>1a鐨勬哀鍖栬繕鍘熸儏鍐点€傚浘鐗囨潵婧愶細J. Am. Chem. Soc.

闅忓悗浣滆€呰浆鑰屾帰绱㈠簳鐗╂鞍鍩哄寲鐨勬渶浣虫潯浠讹紝浠ョ煶澧ㄧ數鏋佸拰Pt鐢垫瀬鏋勬垚鐢佃В姹狅紝鍦ㄦ亽瀹氱數娴侊紙1-3 mA锛変笅鍙嶅簲锛孴MSCN浣滀负姘板熀鏉ユ簮銆備粬浠渶鍒濆皾璇曞湪鐢垫瀬涓婅繘琛屽簳鐗╃殑鐩存帴姘у寲锛屼骇鐗?strong>2a浜х巼杈冧綆锛?9%锛宔ntry 1锛夈€傚弽搴斾腑鍔犲叆10 mol%鐨凙BNO锛?strong>2a鐨勪骇鐜囩炕鍊嶏紙37%锛宔ntry 2锛夈€傚弽搴斾腑鍔犲叆1鍖栧璁￠噺鐨勫叚姘熷紓涓欓唶锛圚FIP锛夊彲浣滀负璐ㄥ瓙婧愪績杩涢槾鏋丠₂鐨勪骇鐢熴€?/p>

浠栦滑杩樺鍏跺畠姘哀鍖栫墿杩涜鑰冨療锛孴EMPO鍜?-涔欓叞姘ㄥ熀TEMPO锛圓CT锛夊叿鏈夋瘮ABNO鏇撮珮鐨勬哀鍖栬繕鍘熺數鍔匡紝浣嗕骇鐜囪緝浣庯紙entry 4鍜?锛夈€侹etoABNO鍙備笌鍙嶅簲鍏锋湁鏈€楂樼殑浜х巼锛屼絾鐢变簬鍏舵哀鍖栬繕鍘熺數鍔胯緝楂橈紝鍙兘浼氬奖鍝嶅畼鑳藉洟鐨勫吋瀹规€с€傚弽搴斿皢鐢佃В鐢垫祦浠? mA澧炲姞鍒? mA锛屼骇鐜囦粠54%澧炲姞鍒?6%锛坋ntry 3鍜?锛夈€備粬浠繕浣跨敤MeOH鏇夸唬HFIP浣滀负璐ㄥ瓙娣诲姞鍓傦紝骞跺皢鍏跺寲瀛﹁閲忛檷浣庤嚦0.5褰撻噺锛屾渶缁堜互84%鐨勪骇鐜囧緱鍒扮洰鏍囦骇鐗╋紙entry 7-10锛夈€傚弽搴斾互1 g閲忕骇瑙勬ā杩涜锛坋ntry 11鍜?2锛変篃鑳戒互鑹ソ鐨勬敹鐜囧緱鍒?strong>2a銆?/p>

鍥?. 鐢佃В鏉′欢鐨勪紭鍖栥€傚浘鐗囨潵婧愶細J. Am. Chem. Soc.

鍦ㄤ紭鍖栫殑鍙嶅簲鏉′欢锛堢孩鑹茬嚎锛変笅锛岀淮鎸? mA鐢垫祦鎵€闇€鐨勭數鏋佺數鍔胯緝浣庯紙绾︿负3 mA锛夈€傚湪涓嶅瓨鍦∕eOH锛堣摑鑹茬嚎锛夌殑鎯呭喌涓嬶紝鍙湁褰撻€氳繃鐨勭數鑽峰皬浜嶢BNO鐢靛寲瀛︽哀鍖栬嚦ABNO⁺鎵€闇€鐨勭數鑽锋椂锛屾墠鑳借瀵熷埌杈冧綆鐨勭數鍔裤€傚湪涓嶅瓨鍦∕eOH鍜孉BNO锛堢豢鑹茬嚎锛夌殑鎯呭喌涓嬶紝鍙嶅簲鍒欓渶瑕佹洿楂樼殑鐢垫瀬鐢靛娍鏉ョ淮鎸? mA鐢垫祦锛屽垵濮嬭娴嬪埌鐨勭數鍔夸笌CV鐮旂┒涓殑鏈熸湜鍊兼帴杩戙€傜劧鑰岋紝鍦ㄥ疄闄呭弽搴旇繃绋嬩腑锛岃鐢靛娍鏄捐憲涓婂崌锛屽彲鑳芥槸鐩存帴鐢佃В杩囩▼涓骇鐢熺殑鍙嶅簲涓棿浣撳鐢垫瀬姹℃煋閫犳垚鐨勩€傚弽搴旂殑浜х巼涓庣淮鎸佽鍙嶅簲鎵€闇€鐨勭數鍔挎垚鍙嶆瘮锛岃〃鏄庡湪闈為殧绂荤數姹犱腑锛屾爱姘у寲鐗╀笌璐ㄥ瓙绌挎杩囩▼闇€瑕佸緢濂藉湴鍖归厤鎵嶈兘鎻愰珮浜х巼銆?/p>

鍥?. 鎭掓祦鐢佃В杩囩▼鐨勫垎鏋愩€傚浘鐗囨潵婧愶細J. Am. Chem. Soc.

鏈変簡鏈€浣崇殑鍙嶅簲鏉′欢锛屼綔鑰呭搴曠墿鐨勯€傜敤鑼冨洿杩涜浜嗚€冨療锛堝浘5A锛夈€傚浜?-鍙栦唬鐨勫搶鍟剁被鍖栧悎鐗╋紝涓嶅悓瀹樿兘鍥慨楗扮殑搴曠墿锛屽寘鎷姵鍩恒€佽姵鍩哄崵鍖栫墿銆佽姵鍩洪啔銆侀叞鑳恒€侀叝銆佸悺鍟跺拰鐩稿叧鐨勬潅鑺冲熀琛嶇敓鐗╀互鍙婂伓姘被鍖栧悎鐗╋紙3a-3r锛夛紝鍙備笌鍙嶅簲閮借兘鑾峰緱鑹ソ鐨勪骇鐜囥€傝鏂规硶鐢氳嚦鑳藉鍏煎娓哥鐨勪簩绾х緹鍩猴紙3x锛夛紝琛ㄦ槑鑳烘哀鍖栫殑杩囩▼浼樺厛浜庢爱姘у寲鐗╀粙瀵肩殑閱囨哀鍖栥€傚弽搴旀贩鍚堢墿涓洖鏀剁殑鐢佃В璐ㄧ洂锛圱BAPF₆锛夎繕鍙互閲嶅浣跨敤銆傚簳鐗╀腑瀛樺湪澶т綅闃诲彇浠ｅ熀锛?strong>3a-3p锛?s锛夋椂锛屽弽搴斿彲浠ュ緱鍒拌緝楂樼殑闈炲鏄犻€夋嫨鎬э紝閫氬父鍙緱鍒板崟涓鏄犱綋銆備綔鑰呴€氳繃NOE鍜屽崟鏅惰灏勭粨鏋勫垎鏋愶紝璇佸疄浜嗘鞍鍩轰笌涓嶅悓鍙栦唬鍩轰箣闂村瓨鍦ㄨ壇濂界殑鍙嶄綅鍏崇郴銆傜珛浣撳寲瀛﹀垎鏋愯〃鏄庯紝姘板寲鐗╁浜氳兒涓棿浣撹繘琛岃酱鍚戣繘鏀伙紝璇ュ弽搴旀ā鍨嬩笌Houk鍜孋ieplak鏇炬姤閬撶殑绔嬩綋鍖栧妯″瀷涓€鑷淬€傝鏂规硶杩橀€傜敤浜庡搶鍟剁被鍖栧悎鐗╀互澶栫殑鏉傜幆鍖栧悎鐗╋紝濡傚悺鍜兎锛?strong>3ac锛夈€佸悧鍟夛紙3u锛夈€?/p>

鍥?. 搴曠墿閫傜敤鑼冨洿鐨勮€冨療銆傚浘鐗囨潵婧愶細J. Am. Chem. Soc.

瀵逛簬鍚屾椂鍚湁淇濇姢鍩轰慨楗板拰娓哥姘殑浜岀骇鍝屽暥绫诲簳鐗╋紝姘板熀鍖栧彧鍙戠敓鍦ㄦ湭淇濇姢鐨勫搶鍟剁幆锛?strong>3q锛変笂銆傚彟涓€鏂归潰锛屽惈鏈変簲銆佸叚鍏冪幆涓夌骇鐑锋皑鍩哄彇浠ｇ殑浜岀骇鍝屽暥搴曠墿锛?strong>3z锛?strong>3aa锛夊湪鐑锋皑鍩虹幆涓婁紭鍏堝彂鐢熸鞍鍩哄寲鍙嶅簲銆傝繖绉嶆柟娉曞湪鑽墿鍖栧涓篃鍙互寰楀埌鍏呭垎鐨勫埄鐢紝鍙嶅簲鑳界洿鎺ュ娲绘€ц嵂鐗╁拰鍊欓€夎嵂鐗╁垎瀛愬鍒╁煿閰紙3j锛夈€?绉嶅彈浣撴嫯鎶楀墏锛?strong>3p鍜?strong>3r锛夊拰鎶桯IV鑽墿Nelfinavir锛?strong>3i锛夌瓑杩涜琛嶇敓鍖栥€傛姉鎶戦儊鑽墿鍒嗗瓙闃跨背鎷夋硶涓侊紙3ad锛夊彂鐢熸鞍鍩哄寲涔熻兘鍙栧緱48%鐨勬敹鐜囥€傛鞍鍩烘按瑙ｄ负缇ч吀杩樺彲浠ョ敤浜庡悎鎴愮浉搴旂殑闈炲ぉ鐒舵皑鍩洪吀锛屽嚑绉嶆鞍鍖栦骇鐗╄兘鐩存帴鍦ㄤ笉鍒嗙鐨勬潯浠朵笅姘磋В鐢熸垚鐩稿簲鐨勭晶閰歌鐢熺墿锛?strong>4a-d锛屽浘5B锛夈€?/p>

鎬荤粨

Shannon S. Stahl鏁欐巿璇鹃缁勫彂灞曚簡涓€绉嶉珮鏁堛€佺幆澧冨弸濂界殑鏂规硶鐢ㄤ簬浜岀骇鍝屽暥绫诲寲鍚堢墿鐨勭數鍖栧伪-姘板熀鍖栵紝鍙敤浜庡悎鎴愪竴绯诲垪閲嶈鐨勮嵂鐗╃爩鍧椼€侫BNO鍙備笌姘㈣浆绉昏繃绋嬪彲浣垮弽搴斿湪浣庣數鏋佺數鍔夸笅杩涜锛屽叿鏈夎壇濂界殑瀹樿兘鍥㈠吋瀹规€с€傝鏂规硶鍦ㄨ嵂鐗╃爺鍙戜腑鍏锋湁鍗佸垎閲嶈鐨勫簲鐢ㄤ环鍊笺€?/p>

鍘熸枃

Electrochemical Aminoxyl-Mediated 伪-Cyanation of Secondary Piperidines for Pharmaceutical Building Block Diversification

J. Am. Chem. Soc., 2018, 140, 11227, DOI: 10.1021/jacs.8b08145

瀵煎笀浠嬬粛

Shannon S. Stahl

http://www.x-mol.com/university/faculty/98